Purpose: To report the efficacy and safety of trans-epithelial (epi-on) corneal cross-linking (CXL) for keratoconus, and compare the outcomes with that of the epithelium-off (epi-off) CXL. Methods: Data from 18 practices in Australia and Italy were included. Thirty-three eyes underwent epi-on CXL (mean age 27.7 ± 11.0 years; female 35; 61 CXL with ultraviolet-A power 45 mW/cm~2 for 2 minutes) and 619 eyes underwent epi-off CXL (mean age 27.2 ± 11.3 years; female 31; 73 cases with ultraviolet-A power 9 mW/cm~2 for 10 minutes). Outcome measures included changes in visual acuity (VA), keratometry, minimum corneal thickness (MCT), and frequency of adverse events. Results: Epi-on CXL was undertaken in milder cases (mean baseline values for epi-on and epi-off CXL respectively: VA 70.1 ± 21.2 vs 62.2 ± 20.3 logMAR letters, Kmax 52.2 ± 11.3 vs 58.0 ± 8.6D, K2 48.6 ± 8.5 vs 50.8 ± 6.2D, MCT 457.6 ± 63.2 vs 455.6 ± 46.4μm (p 0.05). The keratometry outcomes showed more flattening for epi-off than for the epi-on CXL (mean change in Kmax with epi-off CXL, -0.7 (-1 to -0.4) D; p = 0.05). Two (6.1) eyes with epi-on CXL and 108 (17.4) eyes with epi-off CXL had clinically significant haze. Conclusions: Epi-on CXL produced less haze and did not produce corneal flattening.
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