Collagenase-Mediated Tissue Modeling of Corneal Ectasia and Collagen Cross-Linking Treatments

PURPOSE. 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. (Invest Ophthalmol Vis Sci. 2012; 53: 2321-2327) DOI:10.1167/iovs.11-9327