Outcomes Of Accelerated Corneal Cross-Linking With Hypo-Osmolar Riboflavin In Sub-400 Micron Corneas: A Comparative Analysis Based On Intraoperative Corneal Thickness

To evaluate the safety and efficacy of accelerated corneal collagen cross-linking (ACCL) using hypo-osmolar riboflavin solution (HRS) in patients with corneal thickness (CT) below 400 micron (µm) and to compare outcomes between keratoconus (KC) patients whose intraoperative CT remained below or exceeded 400 µm.

This retrospective, non-randomised study included 76 eyes of 69 patients with progressive KC who underwent ACCL using HRS between April 2021 and April 2024 at our clinic, a tertiary eye care center.

HRS was applied to the patients at 30-second intervals for a total duration of 15 minutes, along with UVA irradiation at 18 mW/cm² for 5 minutes. Patients were divided into two groups: Group 1, in which CT remained below 400 µm despite HRS application, and Group 2, in which CT exceeded 400 µm following HRS application. Endothelial cell density (ECD), uncorrected (UCVA) and best-corrected visual acuity (BCVA), refractive outcomes, topographic parameters, and higher-order aberrations (HOAs) were evaluated at baseline and at 3, 6, and 12 months postoperatively. Statistical analysis was performed using independent-samples t-tests, repeated measures ANOVA, and post-hoc Bonferroni corrections.

In both groups, there was no significant difference in ECD between preoperative and postoperative month 12 values (p=0.504 and p=0.695, respectively). UCVA and BCVA significantly improved in both groups at 12 months (each p<0.05), with no significant differences between the groups (p>0.05). Spherical, cylindrical, and spherical equivalent values showed no significant changes postoperatively (each p>0.05). Kmax reduction at 12 months was significant in Group 1 (p=0.014), whereas Group 2 exhibited stabilization (p=0.064). HOAs showed no significant changes in either group at month 12 (each p>0.05). Permanent corneal haze developed in 4 patients (2 patients from each group); however, none required ACCL repeat or corneal transplantation.

ACCL using HRS appears to be a safe and effective treatment for progressive KC in thin corneas while preserving endothelial integrity. The comparable visual and topographic outcomes between groups suggest that ACCL remains effective even when intraoperative CT remains below 400 µm.