Effect Of Iontophoresis Parameters On The Cross-Linking Effect Of Riboflavin-Ultraviolet A Scleral Cross-Linking

China is a typical country with a high incidence of high myopia,and it shows a trend of younger age.High myopia has become one of the main eye diseases causing blindness in China,but there is no effective treatment at present.Sclera crosslinking is expected to be a promising method for the treatment of high myopia in clinical application.Drug ion delivery method was introduced into crosslinking due to its non-invasibility,aiming to enhance the molecular penetration into tissues by using small current to improve the efficacy of crosslinking.However,there are many factors affecting ion transfer,such as current time,current intensity and parasitic ions.The effect of parasitic ions and time of implantation on scleral application of this technique is not clear.In this study,the effects of parasitic ion riboflavin solution and iontophoresis time on the permeability of riboflavin and the mechanical effect of riboflavin-UVA scleral cross-linking were studied by experiments and simulations,in order to optimize the parameters of ion delivery and provide a reference for the eventual clinical application of scleral cross-linking.The main work and conclusions are as follows:（1）The effects of parasitic ions on the delivery efficiency of riboflavin and the mechanical properties of scleral tissue after cross-linking were studied.Riboflavin penetration in scleral tissues was observed by fluorescence microscopy after the ions of Ringer’s solution and riboflavin saline solution were introduced into scleral tissues for 10 min.The concentration of riboflavin solution was determined by HPLC.The scleral tissue was cross-linked with riboflavin by iontophoresis,and the mechanical properties of scleral tissue were detected by uniaxial tensile method.The results showed that Ringer’s solution of riboflavin lactate contained more kinds of parasitic ions than that of riboflavin normal saline.The results of average fluorescence intensity,penetration depth,concentration and elastic modulus of sclera after UVA irradiation showed that the effect of ion transfer of riboflavin normal saline was better than that of Ringer’s solution of riboflavin lactate.These results suggest that the content of parasitic ions may affect the mechanical properties of scleral tissues after cross-linking by affecting the introduction of riboflavin.This study can provide a reference for improving riboflavin import efficiency and optimizing riboflavin formulation.（2）The riboflavin penetration depth,percentage of penetration depth and penetration rate were measured after the ions were introduced into the sclera for 2.5,5,7.5 and 10 min,respectively.The mechanical properties of the sclera after UVA irradiation were analyzed by uniaxial tensile method.The results showed that there was no significant change in the effect of riboflavin iontophoresis and the mechanical properties of sclera after UVA irradiation at 2.5min;compared with 5 min,the penetration of riboflavin was deeper at 10 min,and the mechanical properties of sclera tissue at this time were significantly improved compared with5 min,indicating that 10 min was the optimal time for the four time points in this experiment.（3）Using COMSOL Multiphysics software,the effects of different diffusion coefficients（2D₀,D₀,D₀/2,D₀/3 and D₀/4）and permeation time（2.5 min,5 min,7.5 min and 10 min）on the permeability of riboflavin solution in scleral tissue were simulated and compared with the experimental results.The results showed that the diffusion coefficient of the riboflavin lactate Ringer solution was about D0/3,and that of the riboflavin saline was about D0/2,indicating that the riboflavin saline diffused faster,which was consistent with the conclusion（1）.Moreover,from the lateral to the medial side of the sclera,the penetration concentration and depth of riboflavin increased with the increase of the diffusion coefficient and the penetration time of riboflavin solution.The simulation results of the penetration depth with time were consistent with the conclusion（2）,indicating that the model can be used to predict the penetration depth of riboflavin solution during scleral cross-linking.The relationship between riboflavin parameters and scleral biomechanical properties after violet diplomatic coupling was preliminarily obtained in the above study,which provided a reference for the controllability and predictability of scleral crosslinking degree.