Morphological and functional correlations in riboflavin UV A corneal collagen cross-linking for keratoconus

Acta Ophthalmol. 2012 May;90(3):259-65. doi: 10.1111/j.1755-3768.2010.01890.x. Epub 2010 Apr 23.


Purpose: To investigate the correlations between corneal structural modifications assessed by in vivo corneal confocal microscopy with visual function [uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA)] and morphological data (corneal topography, pachymetry, elevation analysis) after riboflavin UV A corneal collagen cross-linking (CXL) for the stabilization of progressive keratoconus.

Methods: Forty-four eyes with progressive keratoconus were enrolled in the Siena Eye Cross Study (prospective nonrandomized phase II open trial). All eyes underwent Riboflavin UV A CXL. Preoperative and postoperative evaluation comprised: UCVA, BSCVA, optical pachymetry (Visante OCT, Zeiss, Germany), corneal topography (CSO, Florence, Italy) and tomography (Orbscan IIz; B&L, Rochester, NY, USA) and in vivo confocal microscopy (Heidelberg Retina Tomograph II; Rostock, Heidelberg Gmbh, Germany). Examinations were performed preoperatively 6 months and one day before treatment and at 1, 3, 6 and 12 months of follow-up.

Results: In vivo corneal confocal microscopy showed time-dependent postoperative epithelial and stromal modifications after cross-linking. Epithelial thinning associated with stromal oedema and keratocytes apoptosis explained initial tendency towards slightly reduced VA and more glare one month postoperatively in 70% of eyes. Furthermore, a statistically not significant early worsening of topographic mean K values was observed. Orbscan II analysis significantly underestimated pachymetric values after treatment. Pachymetric underestimation was rectified by high-resolution optical pachymetry provided by the Visante OCT system. After the third post-CXL month, epithelial thickening, disappearance of oedema and new collagen compaction recorded by in vivo corneal confocal microscopy explained the improvements in visual performance during the follow-up. Changes in stromal reflectivity and collagen compaction observed by in vivo confocal microscopy were associated with corneal flattening and reduction in anterior elevation values recorded by differential topographic analysis.

Conclusion: Corneal structural changes assessed by in vivo corneal confocal microscopy demonstrated significant correlations with visual function (UCVA and BSCVA) and morphological (corneal topography, pachymetry, elevation analysis) findings recorded after riboflavin-UV A-induced CXL.

Publication types

  • Clinical Trial, Phase II
  • Controlled Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Collagen / metabolism*
  • Cornea / metabolism
  • Cornea / pathology*
  • Corneal Stroma / metabolism
  • Corneal Topography
  • Cross-Linking Reagents / therapeutic use*
  • Humans
  • Keratoconus / drug therapy
  • Keratoconus / metabolism
  • Keratoconus / physiopathology*
  • Microscopy, Confocal
  • Photochemotherapy
  • Photosensitizing Agents / therapeutic use*
  • Prospective Studies
  • Riboflavin / therapeutic use*
  • Ultraviolet Rays
  • Visual Acuity / physiology*
  • Young Adult


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