A theoretical model for optimizing UVA/riboflavin crosslinking

Ultraviolet-A and riboflavin (UVA/R) crosslinking has emerged as a valuable technique for ocular disease treatments. However, the exact influence of the oxygen and riboflavin on the crosslinking has not been fully explored so far. A kinetic model was developed to predict corneal/scleral stiffening effects under varying oxygen levels, irradiation intensities, and riboflavin solution concentrations during crosslinking at a fixed fluence. The optical properties of porcine sclera were determined by UV-Vis spectrophotometry. Monte Carlo method was employed to evaluate intrastromal light absorption of riboflavin. The roles of oxygen and riboflavin in the reaction mechanism were proposed based on the kinetic interactions of reactive species within the corneal/scleral stroma. Kinetic simulations indicated that increasing intrastromal oxygen concentration, driven by higher ambient oxygen levels, significantly improves crosslinking efficiency. The crosslinker formation rate reach its maximum when the intrastromal riboflavin concentration was approximately 0.245 %. Concentrations that are either too low or too high are adversely affect the formation of crosslinker. Optimal stiffening effects could be achieved by balancing oxygen availability, irradiation intensity, and riboflavin solution concentration. The model accuracy of oxygen prediction was verified by experimental results obtained from corneal crosslinking. Linear correlations were found between the model-predicted concentration of newly induced crosslinkers and the experimentally measured mechanical properties of both the cornea and sclera under various crosslinking protocols. Our study improved the prediction model by introducing accurate optical properties of the sclera. This proposed model provides a possibility for predicting the biomechanical crosslinking efficacy of the cornea/sclera, and may be used for optimizing UVA/R crosslinking protocols in customized treatment for ocular disease.