Aim To evaluate two different techniques of cross-linking: standard epithelium-off (CXL epi-off) versus transepithelial (CXL epi-on) cross-linking in patient with progressive keratoconus. Methods Forty eyes from 32 patients with progressive keratoconus were prospectively enrolled from June 2014 to June 2015 in this nonblinded, randomized comparative study. Twenty eyes were treated by CXL epi-off and 20 by CLX epi-on, randomly assigned, and followed for 2 years. All patients underwent a complete ophthalmologic testing that included uncorrected and best corrected visual acuity, central and peripheral corneal thickness, corneal astigmatism, simulated maximum, minimum, and average keratometry, corneal confocal microscopy, Schirmer I and break-up time (BUT) tests, and the Ocular Surface Disease Index. Intra- and postoperative complications were recorded. The solution used for CXL epi-off comprised riboflavin 0.1% and dextran 20.0% (Ricrolin), whereas the solution for CXL epi-on (Ricrolin TE) comprised riboflavin 0.1%, dextran 15.0%, trometamol (Tris), and ethylenediaminetetraacetic acid. Ultraviolet-A treatment was performed with a UV-X system at 3 mW/cm2. Results In both groups, a significant improvement in visual function (Group 1: baseline 0.36 ± 0.16 logMAR, two-year follow-up 0.22 ± 0.17 logMAR, p=0.01; Group 2: baseline 0.32 ± 0.18 logMAR, 2-year follow-up 0.27 ± 0.19 logMAR, p=0.01) was recorded. Keratometry remained unchanged in both groups. The mean corneal thickness showed a significant reduction (mean difference of corneal thickness: −55 micron and −71 micron, resp.). One-month after treatment, OSDI© reached 13.56 ± 2.15 in Group 1 (p=0.03) and 11.26 ± 2.12 in Group 2 (p=0.04). At confocal microscopy, abnormal corneal nerve alterations were found in both groups. Fibrotic reaction (43.75%) and activated keratocyte (62.6%) were more commonly recorded in Group 1 than in Group 2 (25.0% and 18.75%), with p=0.668 and 0.356, respectively. Conclusion Our findings demonstrate that both procedures are able to slow keratoconus progression. Both treatment modalities are equivalent in terms of results and related complications. CXL epi-on technique is preferable to CXL epi-off since it preserves the corneal thickness and improves visual acuity, also reducing the postoperative ocular discomfort during the study period.
