Photochemical Kinetic Modeling for Oxygen-enhanced UV-light-activated Corneal Collagen Crosslinking

Aims: To derive analytic formulas for the efficacy of type-II corneal collagen crosslinking (CXL) based on coupled macroscopic kinetic equations with an emphasis on the role of oxygen.

Study Design: modeling and analysis of type-II CXL

Place and Duration of Study: Taipei, Taiwan, between Feb. and June 2017.

Methodology: Coupled macroscopic kinetic equations are derived under the quasi-steady state condition. For type-I CXL, the riboflavin triplet state [RF3] interacts directly with the stroma collagen substrate for crosslinking. For type-II process, [RF3] interacts with the ground-state oxygen [O2] to form a reactive oxygen singlet (ROS) which can relax to [O2], or interact with the extracellular matrix for crosslinking.

Results: Both type-I and type-II efficacy are nonlinear increasing function of the UV light dose (or fluence). Oxygen is required for type-II CXL, but not absolutely needed in type-I CXL. With the presence of oxygen external source, the steady-state type-II efficacy is a decreasing function of the UV intensity (for the same dose), same as that of type-I. Sufficient external oxygen supply, either pre-CXL or during CXL, will enhance the CXL overall efficacy. UV light in pulsing-mode may also improve the efficacy, but only when UV-off period is long enough for oxygen replenishment. Thin cornea (under the safety thickness criteria), low UV intensity (3 to 18 mW/cm2), and epi-off CXL will achieve higher overall efficacy than that of thick corneas, or epi-on CXL under high intensity (>18 mW/cm2).

Conclusion: We have derived analytic formulas for the efficacy of type-I and type-II CXL. The overall CXL efficacy is proportional to the UV light dose (or fluence), the riboflavin and oxygen initial concentration and their diffusion depths in the stroma.