title: Transepithelial corneal collagen crosslinking for keratoconus: qualitative investigation by in vivo HRT II confocal analysis.
abstract: OBJECTIVE
  This was a qualitative investigation of corneal microstructural modifications in keratoconic patients undergoing experimental transepithelial crosslinking (TE CXL).
  
  
  METHODS
  Ten patients with keratoconus intolerant to gas-permeable rigid contact lenses were enrolled. Corneal thickness was in the range 350-390 µm at the thinnest point measured by Visante AC optical coherence tomography system (Zeiss, Jena, Germany). All patients underwent TE CXL with 0.1% riboflavin-15% dextran solution supplemented with TRIS plus sodium EDTA (Ricrolin TE, Sooft Italia) according to Siena protocol. In vivo Heidelberg retinal tomograph II laser scanning confocal analysis (Rostock Cornea Module, Heidelberg, Germany) was performed with the following follow-up: preoperative and postoperative assessments at 1, 3, and 6 months. The following morphologic parameters were evaluated: epithelium, subepithelial, and anterior stroma nerve plexi, keratocytes apoptosis, stromal changes, and the endothelium.
  
  
  RESULTS
  After TE CXL, epithelial cells showed apoptosis, with mosaic alterations gradually disappearing. Keratocytes apoptosis was variable, superficial, and uneven, with a maximum depth of penetration at about 140 µm, measured from the surface of epithelium. Treatment respected subepithelial and stromal nerves that did not disappear. No variation in cell count or endothelial mosaic was observed.
  
  
  CONCLUSIONS
  In vivo confocal analysis of corneal modifications induced by TE CXL showed a limited apoptotic affect of this treatment, about one-third of classic epi-off crosslinking procedure. The TE CXL respected sub-basal and anterior stroma nerve fibers, resulting safe for corneal endothelium. According to limited penetration, its mid- to long-term efficacy needs to be determined in different clinical settings related to patient age and keratoconus progression.
authors.affiliation: Department of Ophthalmology, Siena University, Siena - Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Caporossi
authors.forename: Cosimo
authors.initials: C
authors.lastname: Mazzotta
authors.forename: Stefano
authors.initials: S
authors.lastname: Baiocchi
authors.forename: Tomaso
authors.initials: T
authors.lastname: Caporossi
authors.forename: Anna Lucia
authors.initials: AL
authors.lastname: Paradiso
mesh_terms: D017209:Apoptosis; D003094:Collagen / Q000378:metabolism*; D060527:Corneal Keratocytes / Q000473:pathology; D003319:Corneal Stroma / Q000294:innervation / Q000378:metabolism / Q000473:pathology*; D003432:Cross-Linking Reagents / Q000378:metabolism*; D003941:Diagnostic Techniques, Ophthalmological; D019573:Epithelium, Corneal / Q000378:metabolism; D006801:Humans; D007640:Keratoconus / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018613:Microscopy, Confocal; D009882:Ophthalmic Nerve / Q000473:pathology; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012256:Riboflavin / Q000627:therapeutic use; D014466:Ultraviolet Rays
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D003094:Collagen; D012256:Riboflavin