Oxygen Diffusion May Limit the Biomechanical Effectiveness of Iontophoresis-Assisted Transepithelial Corneal Cross-linking

Purpose To evaluate the impact of varying treatment time on the efficacy of iontophoresis-assisted transepithelial corneal cross-linking (I-CXL) in ex vivo porcine corneas. Methods One hundred twelve porcine corneas with intact epithelium were divided into 7 groups and analyzed. Groups 1, 2, and 3 received standard epitheliumoff CXL (S-CXL) with hypo-osmolaric 0.1% riboflavin and 30 minutes of ultraviolet-A (UV-A) irradiation at 3 mW/cm2, 10 minutes at 9 mW/cm2, or were not irradiated (controls). Groups 4, 5, 6, and 7 received I-CXL for either 60 minutes at 1.5 mW/cm2, 30 minutes at 3 mW/cm2, 10 minutes at 9 mW/cm2, or were not irradiated (controls). Elastic modulus and stress after relaxation of 5-mm wide corneal strips were analyzed. Results In the S-CXL groups, significant differences (P ≤ .05) in stress-strain extensometry were found between controls and 3 mW/cm2 for 30 minutes (group 1) and between controls and 9 mW/cm2 for 10 minutes (group 2). In the I-CXL groups, only the 1.5 mW/cm2 for 60 minutes setting (group 4) showed a significant stiffening effect. All epithelium-off groups provided a stiffening effect significantly stronger than I-CXL: with a stiffening effect of 149% and 112%, groups 1 and 4 were the groups with greater elastic modulus between the S-CXL and I-CXL groups, respectively. Conclusions The biomechanical effect of I-CXL increased significantly when using a low irradiance/long irradiation setting. Oxygen diffusion thus represents a limiting factor even when riboflavin penetration is improved via iontophoresis. Still less effective than S-CXL, this modification may help establish transepithelial CXL as a treatment option in selected cases. [J Refract Surg. 2018;34(11):768-774.].