Five-year corneal cross-linking outcomes: A Save Sight Keratoconus Registry Study

Clin Exp Ophthalmol. 2023 Jan;51(1):9-18. doi: 10.1111/ceo.14177. Epub 2022 Oct 24.


Background: We aimed to determine the long-term outcomes of epithelium-off cross-linking (CXL) in keratoconus patients.

Methods: An observational registry study from 41 centres across 5 countries was carried out. Primary outcomes included the mean change in visual acuity (VA), Kmax, K2, and thinnest corneal thickness (TCT) at 1-5 years. Secondary outcomes included the percentage of eyes with worsening, stable and improving outcomes.

Results: There were 976 eyes of 794 patients with 1-year of complete follow-up, 501 eyes with 2-years, 355 with 3-years, 235 with 4-years and 162 with 5-years. There was a significant improvement in mean VA from baseline by 3.7 logMAR letters (p < 0.001) in year 1, and 6.9 (p < 0.001) in year 5. Mean Kmax decreased by 1.2 dioptres (D; p < 0.01) in year 1. During subsequent years the Kmax flattening appeared sustained but this was not statistically significant. K2 flattened significantly from baseline in year 1 and then remained stable. At 1 year, 4.1% patients were poor responders to CXL in terms of VA, losing ≥15 letters. The proportion of the poor responders remained unchanged: 4.9% at 5-years. The proportion of poor responders in terms of Kmax remained similar: 5.9% steepening by ≥2D at 1-year and 7.5% at 5-years. The proportion of K2 poor responders remained stable with 4.7% steepening by ≥2D at 1-year and 5.8% at 5-years.

Conclusions: Cross-linking is effective at stabilising keratoconus up to 5 years in most patients. However, a small proportion of eyes failed to stabilise and had reduced vision.

Keywords: adverse events; cross-linking; keratoconus; outcomes.

Publication types

  • Observational Study

MeSH terms

  • Collagen
  • Corneal Cross-Linking
  • Corneal Stroma
  • Corneal Topography
  • Cross-Linking Reagents / therapeutic use
  • Follow-Up Studies
  • Humans
  • Keratoconus* / drug therapy
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use
  • Riboflavin / therapeutic use
  • Ultraviolet Rays


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