Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus

Am J Ophthalmol. 2003 May;135(5):620-7. doi: 10.1016/s0002-9394(02)02220-1.


Purpose: In animal eyes, a significant increase in corneal biomechanical stiffness has been found after collagen crosslinking by combined riboflavin/ultraviolet-A (UVA) treatment. The aim of the present study was to evaluate the clinical usefulness of riboflavin/UVA-induced collagen crosslinking for bringing the progression of keratoconus to a halt.

Design: Prospective, nonrandomized clinical pilot study.

Methods: Twenty-three eyes of 22 patients with moderate or advanced progressive keratoconus (maximum K value, 48-72 diopters) were included. After central corneal abrasion, photosensitizing riboflavin drops were applied and the eyes exposed to UVA (370 nm, 3 mW/cm(2)) in a 1-cm distance for 30 minutes. Postoperative examinations were performed in 6-month intervals, including visual acuity testing, corneal topography, slit-lamp examination, measurement of endothelial cell density, and photographic documentation. The follow-up time was between 3 months and 4 years.

Results: In all treated eyes, the progression of keratoconus was at least stopped. In 16 eyes (70%) regression with a reduction of the maximal keratometry readings by 2.01 diopters and of the refractive error by 1.14 diopters was found. Corneal and lens transparency, endothelial cell density, and intraocular pressure remained unchanged. Visual acuity improved slightly in 15 eyes (65%).

Conclusions: Collagen crosslinking may be a new way for stopping the progression of keratectasia in patients with keratoconus. The need for penetrating keratoplasty might then be significantly reduced in keratoconus. Given the simplicity and minimal costs of the treatment, it might also be well-suited for developing countries. Long-term results are necessary to evaluate the duration of the stiffening effect and to exclude long term side-effects.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Cell Count
  • Collagen / metabolism
  • Collagen / radiation effects*
  • Cornea / drug effects
  • Cornea / metabolism
  • Cornea / radiation effects
  • Corneal Topography
  • Cross-Linking Reagents
  • Endothelium, Corneal / cytology
  • Female
  • Humans
  • Intraocular Pressure
  • Keratoconus / metabolism
  • Keratoconus / physiopathology
  • Keratoconus / therapy*
  • Male
  • Middle Aged
  • Photosensitizing Agents / therapeutic use*
  • Pilot Projects
  • Prospective Studies
  • Riboflavin / therapeutic use*
  • Ultraviolet Rays
  • Visual Acuity


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