title: First proposed efficacy study of high versus standard irradiance and fractionated riboflavin/ultraviolet a cross-linking with equivalent energy exposure.
abstract: OBJECTIVE
  To document the first presented report in December 2008 of high irradiance riboflavin/ultraviolet A (UVA) corneal cross-linking in comparison with that of standard irradiance and of fractionated exposure to increase the time for oxygen diffusion into the cornea.
  
  
  METHODS
  After in vitro studies of oxygen depletion and cross-linking density using type 1 human collagen gels, 36 ex vivo porcine globes were deepithelialized and exposed to 0.1% riboflavin drops in carboxymethylcellulose solution every 5 min for 3 initial doses and then throughout irradiation afterward. Six eyes each were irradiated with 370-nm UVA light at 2, 3, 9, and 15 mW/cm continuously and 15 mW/cm fractionated (with alternate cycles of 30 s "ON" and 30 s "OFF" exposure) using an equivalent radiant exposure of 5.4 mJ/cm. The final six eyes received no UVA exposure as a control. The exposed corneas were then dissected and subjected to extensiometry. Analysis of variance with Bonferroni post hoc test was performed between groups.
  
  
  RESULTS
  The stress required to induce a 10% strain for the control eyes (no UVA) was 100.6±20.9×10 N/m in comparison with the stress of 3 mW/cm (standard irradiation) at 146.7±17.6×10 N/m (P=0.009). The stress at the other equidose irradiances of 2, 9, 15 continuously, and 15 mW/cm fractionated were 140±21.9, 162.8±70, 154.1±70, and 163.0±64×10 N/m, respectively. When comparing the irradiances of 15 mW/cm continuously and fractionated to the standard irradiation, the stress was not statistically different (P=0.799 and 0.643), respectively.
  
  
  CONCLUSIONS
  High irradiance riboflavin/UVA cross-linking with equivalent energy exposure demonstrates comparable efficacy in stiffening corneal collagen with standard irradiance, but with considerably less exposure time. Over the past 6 years, since this report was first presented, the use of high irradiance cross-linking has been gaining popularity.
authors.affiliation: Department of Ophthalmology (R.R.K.), Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cole Eye Institute, Cleveland Clinic, Cleveland, OH; Department of Science and Technology (S.H.), Avedro Inc., Menlo Park, CA; and Department of Natural Sciences (E.S.), Carl Gustav Carus Technical University of Dresden, Dresden, Germany.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Krueger
authors.forename: Satish
authors.initials: S
authors.lastname: Herekar
authors.forename: Eberhard
authors.initials: E
authors.lastname: Spoerl
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D003315:Cornea / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D023421:Models, Animal; D010100:Oxygen / Q000378:metabolism*; D017319:Photosensitizing Agents / Q000494:pharmacology; D012256:Riboflavin / Q000494:pharmacology*; D013314:Stress, Mechanical; D013552:Swine; D014466:Ultraviolet Rays
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D003094:Collagen; D010100:Oxygen; D012256:Riboflavin