title: The Biomechanical Effect of Corneal Collagen Cross-Linking (CXL) With Riboflavin and UV-A is Oxygen Dependent.
abstract: OBJECTIVE
  In an attempt to reduce treatment time in corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A (UV-A), recent protocol modifications include shorter irradiation times at higher fluence, while maintaining constant total applied energy (Bunsen-Roscoe law of reciprocity). While such parameter changes might produce similar biological results within a certain range, the limits of reciprocity are unknown. Limitations in the corneal oxygen diffusion capacity and its potential impact on the efficacy of CXL, raise concerns regarding the efficiency of high-fluence CXL, and also of transepithelial CXL.
  
  
  METHODS
  Porcine corneas were treated with an epithelium-off CXL at a fluence of 9 mW/cm2under two different atmospheres: one with a regular oxygen content (21%) and another in a helium-supplemented, low-oxygen environment (<0.1%). Untreated corneas served as controls (n= 20 each). Five-millimeter corneal stripes were prepared and biomechanical stiffness was measured using an extensometer.
  
  
  RESULTS
  Corneas cross-linked under normal oxygen levels showed a significant increase in biomechanical stability (14.36 MPa ± 2.69 SD), whereas corneas treated similarly, but in a low-oxygen atmosphere showed a Young's modulus similar to untreated controls (11.72 MPa ± 2.77 SD).
  
  
  CONCLUSIONS
  The biomechanical effect of CXL seems to be oxygen dependent. This dependency will be of particular importance in high-fluence and transepithelial CXL and will most likely require major protocol modifications to maintain the efficiency of the method.
  
  
  CONCLUSIONS
  The oxygen dependency of CXL shown here raises concerns about the effectiveness of high-fluence and transepithelial CXL. Both methods were introduced to clinical ophthalmology without thorough validation.
authors.affiliation: Department of Ophthalmology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Richoz
authors.affiliation: Department of Ophthalmology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Arthur
authors.initials: A
authors.lastname: Hammer
authors.affiliation: Department of Ophthalmology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Tabibian
authors.affiliation: Department of Ophthalmology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Zisis
authors.initials: Z
authors.lastname: Gatzioufas
authors.affiliation: Department of Ophthalmology, Geneva University Hospitals, Geneva, Switzerland ; Keck School of Medicine, University of Southern California, Doheny Eye Institute, Los Angeles, CA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Hafezi
keywords: UV-A absorption; corneal collagen cross-linking; helium; high fluence; oxygenation; transepithelial