title: Increased Biomechanical Efficacy of Corneal Cross-linking in Thin Corneas Due to Higher Oxygen Availability.
abstract: OBJECTIVE
  To compare the currently available ultraviolet-A (UV-A) corneal cross-linking (CXL) treatment protocols for thin corneas with respect to oxygen, UV fluence, and osmotic pressure.
  
  
  METHODS
  Freshly enucleated murine (n = 16) and porcine (n = 16) eyes were used. The dependency on oxygen and the amount of UV absorption were evaluated using different CXL protocols, including standard CXL, contact lens-assisted CXL (caCXL), and CXL after corneal swelling. The CXL protocol was adapted from the treatment parameters of the human cornea to fit the thickness of murine and porcine corneas. Immediately after CXL, the corneas were subjected to biomechanical testing, including preconditioning, stress relaxation at 0.6 MPa, and stress-strain extensiometry. A two-element Prony series was fitted to the relaxation curves for viscoelastic characterization.
  
  
  RESULTS
  Standard CXL was most efficient; prior corneal swelling reduced the long-term modulus by 6% and caCXL by 15% to 20%. Oxygen reduction decreased the long-term modulus G∞ by 14% to 15% and the instantaneous modulus G0 by 2% to 5%, and increased the short-term modulus G2 by 22% to 31%. Reducing the amount of absorbed UV energy decreased the long-term modulus G∞ by 5% to 34%, the instantaneous modulus G0 by 7% to 29%, and the short-term modulus G2 by 17% to 20%. The amount of absorbed UV light was more important in porcine than in murine corneas.
  
  
  CONCLUSIONS
  The higher oxygen availability in thin corneas potentially increases the overall efficacy of riboflavin UV-A CXL compared to corneas of standard thickness. Clinical protocols for thin corneas should be revised to implement these findings.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kling
authors.forename: Olivier
authors.initials: O
authors.lastname: Richoz
authors.forename: Arthur
authors.initials: A
authors.lastname: Hammer
authors.forename: David
authors.initials: D
authors.lastname: Tabibian
authors.forename: Soosan
authors.initials: S
authors.lastname: Jacob
authors.forename: Amar
authors.initials: A
authors.lastname: Agarwal
authors.forename: Farhad
authors.initials: F
authors.lastname: Hafezi
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D003315:Cornea / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D063171:Corneal Pachymetry; D003319:Corneal Stroma / Q000378:metabolism; D003432:Cross-Linking Reagents; D004548:Elasticity / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D009997:Osmotic Pressure; D010100:Oxygen / Q000378:metabolism*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D012256:Riboflavin / Q000627:therapeutic use; D034421:Sus scrofa; D014466:Ultraviolet Rays
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D003094:Collagen; D010100:Oxygen; D012256:Riboflavin