title: Collagenase-mediated tissue modeling of corneal ectasia and collagen cross-linking treatments.
abstract: OBJECTIVE
  Corneal collagen cross-linking (CXL) is a method for modifying the natural history of keratoconus and other corneal ectatic diseases. The authors evaluated the use of collagenase for generating an experimental model of ectasia to evaluate the topographic effects of CXL interventions.
  
  
  METHODS
  Nine human corneoscleral specimens unsuitable for transplantation were used. After epithelial debridement, mounting, and pressurization on an artificial anterior chamber, a solution of 10 mg/mL collagenase type II with 15% dextran was applied to five corneas for three hours. Three of these corneas subsequently underwent riboflavin/UV-A CXL. Scheimpflug-based tomography was performed before collagenase exposure, after collagenase exposure, and after CXL to evaluate changes in maximum axial curvature of the anterior surface (K(max)) at three IOP levels. Results were compared to four control eyes exposed to dextran alone.
  
  
  RESULTS
  A statistically significant increase in K(max) was seen across all IOP levels in the collagenase group compared to the control group (+6.6 ± 1.1 diopters [D] and +0.3 ± 0.8 D, respectively, at physiological IOP). After CXL, K(max) decreased (-7.6 ± 2.0 D at physiological IOP). Anterior corneal aberrations increased after collagenase exposure and decreased after CXL. Light microscopy showed loss of normal stromal collagen architecture and localized edema after collagenase exposure.
  
  
  CONCLUSIONS
  A method for generating topographic features of corneal ectasia in human tissue is demonstrated. No significant sensitivity of K(max) to IOP was observed. CXL caused regression of steepening and induced aberrations in this model, consistent with clinical trends. The model may be useful for testing modifications to standard CXL techniques.
authors.affiliation: Lerner College of Medicine, SurgeryInstitute, Cleveland Clinic, Cleveland, Ohio 44120, USA.
authors.forename: Cheng W
authors.initials: CW
authors.lastname: Hong
authors.forename: Abhijit
authors.initials: A
authors.lastname: Sinha-Roy
authors.forename: Lynn
authors.initials: L
authors.lastname: Schoenfield
authors.forename: James T
authors.initials: JT
authors.lastname: McMahon
authors.forename: William J
authors.initials: WJ
authors.lastname: Dupps
mesh_terms: D016022:Case-Control Studies; D003094:Collagen / Q000187:drug effects / Q000378:metabolism*; D017364:Collagenases; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D019781:Corneal Topography; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004108:Dilatation, Pathologic / Q000139:chemically induced; D006801:Humans; D007429:Intraocular Pressure; D008859:Microscopy, Polarization; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012256:Riboflavin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014466:Ultraviolet Rays
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D003094:Collagen; D017364:Collagenases; D012256:Riboflavin