title: Cross-linking with ultraviolet-a and riboflavin reduces corneal permeability.
abstract: OBJECTIVE
  To investigate the effect of cross-linking treatment on corneal permeability in a live animal model.
  
  
  METHODS
  Rabbit eyes were selected at random to be left unoperated or to undergo epithelial debridement with or without treatment consisting of cross-linking (CXL) with riboflavin and ultraviolet-A. Nine eyes received a total dose of 3.6 J/cm² and after epithelial healing the corneas were placed in a two-chamber system for quantification of the diffusion of fluorescein compared with controls. Thirty eyes received a total dose of 5.4 J/cm² and, after epithelial healing, in vivo corneal permeability was quantified as the pupillary response over a 30-minute period to a dose of topical pilocarpine compared with controls.
  
  
  RESULTS
  In the ex vivo assay, the mean permeability coefficient in the CXL group (2.42 × 10⁻⁷) was reduced when compared with the unoperated controls (3.73 × 10⁻⁷; P = 0.007) and to the eyes that received epithelial debridement alone (3.74 × 10⁻⁷; P = 0.01). In the in vivo permeability assay, the change in pupillary diameter at 30 minutes after pilocarpine administration was smaller in the CXL group (-1.9 mm), compared with the epithelial debridement group (-2.6 mm; P < 0.001) and with the unoperated controls (-2.7 mm; P = 0.003).
  
  
  CONCLUSIONS
  Corneal cross-linking with ultraviolet-A and riboflavin results in a statistically significant reduction in corneal permeability. These findings suggest that dosing of topical medications may need to be increased in eyes with a history of CXL to achieve expected therapeutic effects, and they may have implications for the long-term health of the cornea.
authors: Department of Ophthalmology, University of California, San Francisco, San Francisco, California 94143-0730, USA. stewartj@vision.ucsf.edu
authors: Jay M
authors: JM
authors: Stewart
authors: On-Tat
authors: OT
authors: Lee
authors: Fergus F
authors: FF
authors: Wong
authors: David S
authors: DS
authors: Schultz
authors: Ricardo
authors: R
authors: Lamy
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D003315:Cornea / Q000378:metabolism*; D003319:Corneal Stroma / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D003646:Debridement; D005260:Female; D019793:Fluorescein / Q000378:metabolism; D008916:Miotics / Q000493:pharmacokinetics; D010539:Permeability / Q000187:drug effects; D017319:Photosensitizing Agents / Q000494:pharmacology*; D010862:Pilocarpine / Q000493:pharmacokinetics; D011680:Pupil / Q000187:drug effects; D011817:Rabbits; D012256:Riboflavin / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D014466:Ultraviolet Rays
chemical_list: D003432:Cross-Linking Reagents; D008916:Miotics; D017319:Photosensitizing Agents; D010862:Pilocarpine; D003094:Collagen; D012256:Riboflavin; D019793:Fluorescein