Combined Analysis of Safety and Optimal Efficacy in UV-light-activated Corneal Collagen Crosslinking

Abstract

Aims: To analyze the combined factors for safety and optimal efficacy for UV-light-initiated corneal collagen cross-linking (CXL). Study Design: Modeling and analysis of CXL. Place and Duration of Study: New Vision Inc, Taipei, between Oct. 2015 and July 2016. Methodology: Analytic formulas were derived based on the coupled dynamic equations for the safety dose (E*), minimum corneal thickness and concentration of the riboflavin, and the cornea stiffness increase after the CXL. The critical parameters influencing the efficacy of CXL include: various absorption coefficients, initial concentration (C0) and diffusion depth (D) of the riboflavin solution, the quantum yield, the UV light intensity (I0) and dose (E), irradiation duration (t), the cytotoxic threshold dose of endothelial cells(E’) and the corneal thickness (z). Conclusion: The safety dose (E*) is an increasing function of the parameter set (D, z, C0) and has a range of 5.3 to 10.1 J/cm2 for cytotoxicity threshold 0.63 to 1.26 J/cm2. Minimum corneal thickness z* =(300, 400) um for dose of E*=(5.0, 10.1) J/cm2 which has a much wider range than the conventional safety dose 5.4 J/cm2 (with z*=400 um). For maximum efficacy, the optimal dose is 0.7 to 1.55 J/cm2. However, to achieve crosslink depth of  230  to 300 um, higher dose of 2.0 to 3.0 J/cm2 is recommended.