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Mikhail Smirnov, Pavel Kamaev, William A Eddington, Sarah Peterson, Marc D Friedman, David Muller; Riboflavin aggregation and its implications for corneal cross-linking. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3005.
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© ARVO (1962-2015); The Authors (2016-present)
Aggregation of riboflavin (Rf) molecules into clusters may impede the efficacy of highly concentrated Rf solutions in corneal cross-linking (CXL). For a 0.1% solution, typically used for CXL, ~37% of Rf is in clusters (1). This fraction increases to ~72% for a 0.5% solution (1). The rate constants of aggregation and disaggregation processes are known but the effect of aggregation on light-induced transformations of Rf has not been evaluated. We present a mathematical model of aggregation kinetics of Rf exposed to UVA light. The goal is to evaluate Rf concentration effect on the yield of triplet riboflavin that initiates CXL.
Our model includes UV light propagation in Rf solution with varying concentrations of regular and reduced Rf; optical excitation of Rf monomers with light; quantum transitions between ground, singlet, and triplet states; chemical reactions transferring regular Rf into the reduced form; and aggregation, disaggregation, and diffusion of both the Rf forms in water solution under anaerobic conditions. Mathematically, the model was formulated as a set of partial differential equations in 1D space and was solved with finite-element software (Comsol 5.0).<br /> In order to validate the model the bleaching process of Rf under anaerobic conditions was studied experimentally by irradiating Rf aqueous solutions (0.01, 0.05, 0.1, and 0.5%) in a 200 µm cuvette with a top-hat 365 nm beam, at 3 and 30 mW/cm2 for up to 6 min. The concentrations of regular and reduced Rf forms after light exposure was assessed by measuring transmittance of probe light at 365 and 450 nm.
The measured dependencies of Rf and RfH2 concentrations vs. light dose are in good agreement with calculated data for 0.01, 0.05, and 0.1% solutions. 0.5% solution calculated bleaching rate is slower than measured. If the aggregation process is neglected, the model shows appreciable inaccuracy for concentrations ³0.5%.
Rf aggregation effect is substantial for CXL modeling in the typical Rf concentration range. The present model is accurate for concentrations less than 0.5%, usually the case for CXL procedures. At higher concentrations, disaggregation may be higher than assumed by the model.
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