Safety of UVA-riboflavin cross-linking of the cornea

Cornea. 2007 May;26(4):385-9. doi: 10.1097/ICO.0b013e3180334f78.


Purpose: To study potential damage to ocular tissue during corneal collagen cross-linking (X-linking) by means of the riboflavin/UVA (370 nm) approach.

Methods: Comparison of the currently used technique with officially accepted guidelines regarding direct UV damage and the damage created by the induced free radicals (photochemical damage).

Results: The currently used UVA radiant exposure of 5.4 mJ/cm and the corresponding irradiance of 3 mW/cm2 is below the known damage thresholds of UVA for the corneal endothelium, lens, and retina. Regarding the photochemical damage caused by the free radicals, the damage thresholds for keratocytes and endothelial cells are 0.45 and 0.35 mW/cm, respectively. In a 400-microm-thick cornea saturated with riboflavin, the irradiance at the endothelial level was 0.18 mW/cm, which is a factor of 2 smaller than the damage threshold.

Conclusions: After corneal X-linking, the stroma is depopulated of keratocytes approximately 300 microm deep. Repopulation of this area takes up to 6 months. As long as the cornea treated has a minimum thickness of 400 microm (as recommended), the corneal endothelium will not experience damage, nor will deeper structures such as lens and retina. The light source should provide a homogenous irradiance, avoiding hot spots.

Publication types

  • Review

MeSH terms

  • Animals
  • Collagen / drug effects
  • Collagen / radiation effects
  • Cornea / drug effects*
  • Cornea / radiation effects*
  • Corneal Stroma / drug effects
  • Corneal Stroma / radiation effects
  • Cross-Linking Reagents*
  • Endothelium, Corneal / drug effects
  • Endothelium, Corneal / radiation effects
  • Fibroblasts / drug effects
  • Fibroblasts / radiation effects
  • Free Radicals
  • Humans
  • Photochemotherapy*
  • Photosensitizing Agents / adverse effects*
  • Radiation Tolerance
  • Riboflavin / adverse effects*
  • Ultraviolet Rays / adverse effects*


  • Cross-Linking Reagents
  • Free Radicals
  • Photosensitizing Agents
  • Collagen
  • Riboflavin