title: Corneal Cross-Linking for Pediatric Keratoconus: Long-Term Results.
abstract: OBJECTIVE
  To assess the efficacy and safety of cross-linking in pediatric patients with keratoconus and to provide a systematic literature overview regarding this subject.
  
  
  METHODS
  In this prospective cohort, 54 eyes of 36 pediatric patients with keratoconus underwent standard epithelium-off cross-linking. Follow-up measurements taken up to 5 years after treatment were compared with baseline values. Logistic regression was used to identify the underlying cause in case of progression despite treatment. Finally, a systematic search was performed in PubMed and Embase, and data were extracted and summarized.
  
  
  RESULTS
  At all follow-up visits up to 5 years, maximum keratometry values improved significantly (mean change at 5 years -2.06 diopters (D), P = 0.01); moreover, average keratometry, uncorrected distance visual acuity, and corrected distance visual acuity improved at all follow-up times, though not always to the level of statistical significance. In 12 eyes (22%), keratoconus had progressed by ≥1.0 D by the last follow-up visit, despite corneal cross-linking. Cones that were more decentralized were identified as the underlying cause of disease progression. The systematic search yielded 17 unique articles: 10 articles on epithelium-off cross-linking, 2 on accelerated cross-linking, 2 on transepithelial cross-linking, 1 on both epithelium-off and transepithelial cross-linking, and 2 on transepithelial cross-linking with iontophoresis.
  
  
  CONCLUSIONS
  Our long-term follow-up reveals that epithelium-off cross-linking is both apparently safe and effective when used to prevent keratoconus progression in pediatric patients. However, disease progression occurred in 22% of the treated eyes; this progression was attributed to a more decentralized cone location.
authors.affiliation: Utrecht Cornea Research Group, Department of Ophthalmology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Godefrooij
authors.forename: Nienke
authors.initials: N
authors.lastname: Soeters
authors.forename: Saskia M
authors.initials: SM
authors.lastname: Imhof
authors.forename: Robert P L
authors.initials: RP
authors.lastname: Wisse
mesh_terms: D000293:Adolescent; D002648:Child; D015331:Cohort Studies; D003094:Collagen / Q000378:metabolism*; D003319:Corneal Stroma / Q000378:metabolism*; D003432:Cross-Linking Reagents; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007640:Keratoconus / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011446:Prospective Studies; D012256:Riboflavin / Q000627:therapeutic use*; D014466:Ultraviolet Rays
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D003094:Collagen; D012256:Riboflavin