A Transepithelial Corneal Cross-linking (CXL) Protocol Providing the Same Biomechanical Strengthening as Accelerated Epithelium-off CXL

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Purpose To assess the biomechanical strength of a new transepithelial corneal cross-linking (epi-on CXL) protocol without iontophoresis and additional oxygen, and to compare it to the most broadly used accelerated epithelium-off (epioff) CXL protocol. Methods A total of 150 porcine eyes were assigned equally into three study groups: epi-on, epi-off, and control. For the epi-on and control groups, a penetration enhancer solution was applied to the corneal surface before soaking with 0.1% hypo-osmolar riboflavin without carrier. In the epi-off group, a manual abrasion was performed, followed by the application of the same 0.1% hypo-osmolar riboflavin solution. The epi-on and epi-off groups were irradiated at 365-nm ultraviolet-A (UV-A): in the epi-on group, 18 mW/cm 2 pulsed (1 second on-1 second off) UV-A was applied for 15 minutes (fluence 8.1 J/cm 2 ) and in the epi-off group, 9 mW/cm 2 continuous UV-A for 10 minutes were used (fluence 5.4 J/cm 2 ). Stress-strain extensiometry was performed to determine corneal biomechanics. Results The mean elastic modulus (5% and 10% of strain) was 5.21 ± 1.59, 4.95 ± 1.50, and 4.10 ± 1.41 MPa in the epi-on, epi-off, and control groups, respectively. There were no significant differences in the elastic modulus between the two CXL groups ( P = .386), but significant differences were found between both CXL groups and the control group ( P < .001 and P = .005, respectively). Conclusions This new epi-on CXL protocol provides a stiffening effect similar to the most used accelerated epi-off CXL and has the potential to clinically replace the latter, turning CXL into a real office-based procedure without the need for a sterile environment. [ J Refract Surg . 2025;41(7):e724–e730.]