Corneal collagen crosslinking: a systematic review

Ophthalmologica. 2014;232(1):10-27. doi: 10.1159/000357979. Epub 2014 Apr 17.


Keratoconus (KCN) is an ectatic disorder with progressive corneal thinning and a clinical picture of corneal protrusion, progressive irregular astigmatism, corneal fibrosis and visual deterioration. Other ectatic corneal disorders include: post-LASIK ectasia (PLE) and pellucid marginal degeneration (PMD). Corneal crosslinking (CXL) is a procedure whereby riboflavin sensitization with ultraviolet A radiation induces stromal crosslinks. This alters corneal biomechanics, causing an increase in corneal stiffness. In recent years, CXL has been an established treatment for the arrest of KCN, PLE and PMD progression. CXL has also been shown to be effective in the treatment of corneal infections, chemical burns, bullous keratopathy and other forms of corneal edema. This is a current review of CXL - its biomechanical principles, the evolution of CXL protocols in the past, present and future, indications for treatment, treatment efficacy and safety.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Collagen / metabolism*
  • Cornea / physiopathology
  • Corneal Stroma / metabolism*
  • Cross-Linking Reagents / therapeutic use*
  • Elasticity / physiology
  • Humans
  • Keratoconus / drug therapy*
  • Keratoconus / metabolism
  • Keratoconus / physiopathology
  • Photosensitizing Agents / therapeutic use*
  • Riboflavin / therapeutic use
  • Ultraviolet Rays


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