Mohamed Hosny, Moustafa Nour, Sarah Azzam, Mohsen Salem, Esraa El-Mayah Department of Ophthalmology, Cairo University, Giza, Egypt Purpose: The purpose of this study is to compare the efficacy of intratunnel cross-linking combined with intrastromal corneal ring segment (ICRS) implantation versus combined epithelium-off (epi-off) cross-linking and ICRS implantation for the management of keratoconus.Methods: Our study included 20 eyes of 12 patients with moderate-to-severe keratoconus. Group A included 10 eyes that underwent simultaneous ICRS implantation with intratunnel cross-linking. Group B included 10 eyes that underwent simultaneous ICRS implantation with epi-off cross-linking. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest sphere and cylinder, mean and maximum keratometric readings, corneal thickness at pachy apex and thinnest location, as well as corneal hysteresis (CH) and corneal resistance factor (CRF) were compared preoperatively and at 6 months postoperatively.Results: The mean UDVA and CDVA improved significantly in both groups with a statistically nonsignificant difference between the groups (P=0.798 and 0.126, respectively). The manifest cylinder decreased significantly in both groups, while the manifest sphere decreased significantly in Group A but nonsignificantly in Group B with a statistically nonsignificant difference between the groups (P=0.773 and 0.111, respectively). Both techniques led to significant flattening of the cornea and a significant decrease of Km and Kmax with a statistically nonsignificant difference between the groups (P=0.312 and 0.857, respectively). There was a statistically significant decrease in CH in both groups postoperatively; however, there was a statistically nonsignificant increase in CRF after both techniques with a statistically nonsignificant difference between the groups in the mean change of CH and CRF (P=0.633 and 0.313, respectively). No intraoperative or postoperative complications were observed in both groups.Conclusion: Both techniques improved the visual and refractive outcomes in cases of moderate and severe keratoconus with no statistically significant difference between the groups; however, simultaneous intratunnel cross-linking and ICRS implantation showed early visual rehabilitation due to the absence of epithelial defect. Keywords: keratoconus, cross-linking, intratunnel, epi-off, ICRS