Ophthalmology Research: An International Journal

Aims: To derive analytic formulas for the overall efficacy of corneal collagen crosslinking (CXL) based on coupled kinetic equations including both non-oxygen-mediated (NOM) and oxygen-mediated (OM) type-II mechanisms.

Study Design:  modeling the kinetics of CXL.

Place and Duration of Study: Taipei, Taiwan, between June, 2017 and January 2018.

Methodology: Coupled kinetic equations are derived under the quasi-steady state condition for the 3-pathway mechanisms of CXL. For type-I CXL, the riboflavin triplet state [T₃] may interact directly with the stroma collagen substrate [A] under NOM, or with the ground-state oxygen [O₂] to form reactive oxygen species [O-] under OM. For type-II process, [T₃] interacts with [O₂] to form a singlet oxygen [¹O₂]. Both reactive oxygen species (ROS), [O-] and [¹O₂], can relax to [O₂], or interact with the extracellular matrix (or the stroma substrate [A]) for crosslinking.

Results: In the first 3 to 20 seconds, CXL efficacy is governed by both type-I and –II mechanisms, and after that period type-I, NOM is the predominant contribution, while oxygen for OM only plays a limited and transient role, in contrary to the conventionally believed OM-dominant mechanism. The riboflavin profile has a much slower depletion rate than that of oxygen profile. The ratio between NOM-type-I and OM depends on the relative initial concentration of [A] and [¹O₂] and their diffusion depths in the stroma. The overall CXL efficacy is proportional to the UV light dose (or fluence), the riboflavin, C (z, t), and oxygen, [O₂], initial concentration, where efficacy is limited by the depletion of either C (z, t) or [O₂].

Conclusion: Resupply of riboflavin and/or oxygen concentration under a controlled-concentration-method (CCM) during the UV exposure may improve the overall efficacy, specially for the accelerated CXL which has lower efficacy than the standard Dresden low-power (under non-controlled concentration).