title: Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a randomized controlled trial.
abstract: OBJECTIVE
  To compare the clinical effects and safety of transepithelial corneal cross-linking (CXL) to epithelium-off (epi-off) CXL in progressive keratoconus.
  
  
  METHODS
  Randomized clinical trial (noninferiority).
  
  
  METHODS
  Patients received either transepithelial CXL with Ricrolin TE (n = 35) or epi-off CXL with isotonic riboflavin (n = 26) in 1 academic treatment center, using a simple unrestricted randomization procedure. The main outcome measure was clinical stabilization of keratoconus after 1 year, defined as a maximal keratometry (Kmax) increase <1 diopter (D).
  
  
  RESULTS
  Average Kmax was stable at all visits in the transepithelial group, while after epi-off CXL a significant flattening of 1.2-1.5 D was demonstrated from the 3-month follow-up onwards. The trend over time in Kmax flattening was significantly different between the groups (P = .022). Eight eyes (23%) in the transepithelial group showed a Kmax increase of >1 D after 1 year (range 1.3-5.4 D) vs none in the epi-off group (P = .017). There was significant different trend in corrected distance visual acuity (CDVA), with a more favorable outcome in the transepithelial group (P = .023). In the transepithelial group, no complications occurred and in the epi-off group, 4 eyes (15%) developed complications owing to healing problems (sterile infiltrate, herpes keratitis, central haze, and stromal scar).
  
  
  CONCLUSIONS
  This study showed that although transepithelial CXL was a safe procedure without epithelial healing problems, 23% of cases showed a continued keratoconus progression after 1 year. Therefore, at this time, we do not recommend replacing epi-off CXL by transepithelial CXL for treatment of progressive keratoconus.
authors.affiliation: Utrecht Cornea Research Group, Department of Ophthalmology, University Medical Center Utrecht, Utrecht, Netherlands. Electronic address: nsoeters@umcutrecht.nl.
authors.forename: Nienke
authors.initials: N
authors.lastname: Soeters
authors.affiliation: Utrecht Cornea Research Group, Department of Ophthalmology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Robert P L
authors.initials: RP
authors.lastname: Wisse
authors.affiliation: Utrecht Cornea Research Group, Department of Ophthalmology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Daniël A
authors.initials: DA
authors.lastname: Godefrooij
authors.affiliation: Utrecht Cornea Research Group, Department of Ophthalmology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Saskia M
authors.initials: SM
authors.lastname: Imhof
authors.affiliation: Zonnestraal Eye Hospital Amersfoort, Amersfoort, Netherlands.
authors.forename: Nayyirih G
authors.initials: NG
authors.lastname: Tahzib
mesh_terms: D000293:Adolescent; D000328:Adult; D002452:Cell Count; D063171:Corneal Pachymetry; D003432:Cross-Linking Reagents; D018450:Disease Progression; D004728:Endothelium, Corneal / Q000473:pathology; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000601:surgery*; D005260:Female; D006801:Humans; D007429:Intraocular Pressure; D007640:Keratoconus / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use*; D012029:Refraction, Ocular / Q000502:physiology; D012256:Riboflavin / Q000009:adverse effects / Q000627:therapeutic use; D014466:Ultraviolet Rays; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D012256:Riboflavin