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

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Jui-Teng Lin


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.


Corneal crosslinking, corneal keratoconus, efficacy, kinetic modeling, oxygen, riboflavin, ultraviolet light, photodynamic therapy

Article Details

How to Cite
Lin, J.-T. (2017). Photochemical Kinetic Modeling for Oxygen-enhanced UV-light-activated Corneal Collagen Crosslinking. Ophthalmology Research: An International Journal, 7(1), 1-8.
Original Research Article