Epithelium-off versus transepithelial corneal collagen crosslinking for progressive corneal ectasia: a randomised and controlled trial

Br J Ophthalmol. 2017 Apr;101(4):503-508. doi: 10.1136/bjophthalmol-2016-308914. Epub 2016 Jul 7.


Aim: To compare the outcomes of corneal collagen crosslinking (CXL) for the treatment of progressive corneal ectasia using a standard epithelium-off technique versus a transepithelial technique with enhanced riboflavin solution.

Methods: One hundred and forty-four eyes with progressive corneal ectasia were prospectively randomised into a transepithelial CXL study arm or an epithelium-off CXL control arm. Follow-up examinations were set at 3, 6, 12 and 24 months. The primary outcome measure was change in the maximum simulated keratometry value (Ksteep) after 24 months of follow-up. The secondary outcome measure was change in the best spectacle-corrected visual acuity (BSCVA) after 24 months follow-up.

Results: One hundred and thirty-one eyes completed the 24-month follow-up interval. Change in Ksteep was -1.52±0.66 dioptres (D) for the control group versus -0.54±0.58 D for the study group at 24 months of follow-up (p=0.0320). Change in BSCVA was -0.18±0.09 logMAR for the control group versus -0.14±0.08 logMAR for the study group at 24 months of follow-up (p=0.4978). Two eyes in the control group had minor postoperative complications that did not affect the final visual acuity, and one eye in the control group underwent keratoplasty during the study interval.

Conclusions: At 24 months of follow-up, subjects in the epithelium-off CXL group demonstrated a greater improvement in Ksteep compared with subjects in the transepithelial CXL group, but no statistically significant difference in BSCVA was found between groups.

Trial registration number: NCT01708538; pre-results.

Keywords: Cornea.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Collagen / metabolism
  • Cornea / pathology*
  • Corneal Diseases / drug therapy*
  • Corneal Diseases / physiopathology
  • Dilatation, Pathologic / drug therapy*
  • Dilatation, Pathologic / physiopathology
  • Disease Progression
  • Endothelium, Corneal / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Photosensitizing Agents / therapeutic use*
  • Prospective Studies
  • Riboflavin / therapeutic use*
  • Treatment Outcome
  • Young Adult


  • Photosensitizing Agents
  • Collagen
  • Riboflavin

Associated data

  • ClinicalTrials.gov/NCT01708538