Predicting corneal cross-linking treatment efficacy with real-time assessment of corneal riboflavin concentration

Purpose: To assess predictability of tissue biomechanical stiffening induced by UV-A light-mediated real-time assessment of riboflavin concentration during corneal crosslinking (CXL) of human donor tissues. Setting: Studio Italiano di Oftalmologia, Rome, Italy. Design: Laboratory study. Methods: 20 sclerocorneal tissues were randomly stratified to undergo CXL with either the epithelium intact (n = 12) or removed (n = 8). Samples underwent corneal soaking with 0.22% riboflavin formulation (RitSight) with dosing time of t = 10 minutes and t = 20 minutes in epithelium-off and epithelium-on protocols, respectively. All tissues underwent 9-minute UV-A irradiance at 10 mW/cm 2 using theranostic device (C4V CHROMO4VIS). The device used controlled UV-A light irradiation to induce both imaging and treatment of the cornea, providing a real-time measure of corneal riboflavin concentration and treatment efficacy (ie, theranostic score) during surgery. Tissue biomechanics were assessed with an air-puff device (Corvis), which was performed before and after treatment. A 3-element viscoelastic model was developed to fit the corneal deformation response to air-puff excitation and to calculate the mean corneal stiffness parameter (k c ). Results: Significant corneal tissue stiffening ( P < .05) was induced by the theranostic UV-A device in either CXL treatment protocol. Significant correlation was found between the theranostic score and the increase in k c ( R = 0.75; P = .003). The score showed high accuracy (94%) and precision (94%) to predict correctly samples that had improved tissue biomechanical strengthening. Conclusions: Real-time assessment of corneal riboflavin concentration provided a predictive and precise approach for significant improvement of tissue strength on individual corneas, regardless of CXL treatment protocol.