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Silvia Schumacher, Jeremy Wernli, Theo Seiler, Michael Mrochen; Reducing Riboflavin Pre-soaking Time In Corneal Cross-linking. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6807.
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The induction of cross-links during corneal cross-linking depends on the UV-light intensity and riboflavin concentration throughout the corneal tissue. The aim of this work was to investigate the riboflavin concentration distribution throughout the tissue in dependence of the thickness of the layer of applied riboflavin on the stromal surface, the application interval of riboflavin drops, and the pre-soaking time.
A numerical diffusion model was generated based on the one-dimensional diffusion equation. The model considers a diffusion coefficient of D=6.5*10-7 s/cm2 for riboflavin in the corneal stroma and a homogeniouse distributed riboflavin layer at the surface of the cornea. The thickness of the riboflavin surface layer was varied between 50 and 500 μm, the interval of application of additional riboflavin drops between 1 and 5 minutes, and the pre-soaking time between 5 and 30 minutes. Resulting riboflavin concentration distributions were compared with the distribution using the standard treatment protocol (surface riboflavin layer 100 μm, addition drops every 5 minutes, 30 minutes, concentration of Riboflavin solution 0.1%).
The standard protocol results in a riboflavin concentration at the stromal surface of 0.067% (67% of initially applied concentration of 0.1%) and a concentration of 0.036% at a depth of 300 μm within the cornea. By increasing the surface layer to a reservoir of 400 μm thickness, the riboflavin concentration could be increased to 0.091% at the stromal surface and 0.049% at a depth of 300 μm. Applying additional Riboflavin drops at a higher rate of one drop every minute results in an almost identical concentration of 0.093% at the surface and 0.049% at 300 μm. By increasing the thickness of the surface layer to 400 μm and applying riboflavin drops every 5 minutes an equivalent riboflavin distribution to the standard treatment protocol can be achieved, if a pre-soaking time of only 15 minutes combined with an active removal of riboflavin surface layer in combination with a waiting time of 3 minutes before illumination.
In corneal cross-linking, the method of riboflavin application during the pre-soaking-time strongly influences the riboflavin concentration distribution throughout the corneal tissue. Thus, the desired strengthening effect depends on the combination of riboflavin application parameters. Shorter pre-soaking time can be achieved, however, a modification of the riboflavin application protocol can also result in unpredictable outcomes.
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