Corneal cross-linking

Surv Ophthalmol. 2015 Nov-Dec;60(6):509-23. doi: 10.1016/j.survophthal.2015.04.002. Epub 2015 May 14.


Since its inception in the late 1990s, corneal cross-linking has grown from an interesting concept to a primary treatment for corneal ectatic disease worldwide. Using a combination of ultraviolet-A light and a chromophore (vitamin B2, riboflavin), the cornea can be stiffened, usually with a single application, and progressive thinning diseases such as keratoconus arrested. Despite being in clinical use for many years, some of the underlying processes, such as the role of oxygen and the optimal treatment times, are still being worked out. More than a treatment technique, corneal cross-links represent a physiological principle of connective tissue, which may explain the enormous versatility of the method. We highlight the history of corneal cross-linking, the scientific underpinnings of current techniques, evolving clinical treatment parameters, and the use of cross-linking in combination with refractive surgery and for the treatment of infectious keratitis.

Keywords: CXL; accelerated cross-linking; cornea; cross-linking; cross-linking plus; ectasia; infectious keratitis; keratoconus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Collagen / metabolism*
  • Corneal Stroma / metabolism*
  • Cross-Linking Reagents*
  • Elasticity
  • Eye Infections / drug therapy
  • Eye Infections / metabolism
  • Eye Infections / microbiology
  • Humans
  • Keratitis / drug therapy*
  • Keratitis / metabolism
  • Keratitis / microbiology
  • Keratoconus / drug therapy*
  • Keratoconus / metabolism
  • Photosensitizing Agents / therapeutic use*
  • Riboflavin / therapeutic use*
  • Ultraviolet Rays


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