Long-Term Efficacy And Safety Of Epi-On Ionotophoretic Corneal Collagen Cross-Linking With Accelerated Irradiation In Pediatric And Young Adults With Progressive Keratoconus: 9-Year Follow-Up

To assess the long-term efficacy and safety of iontophoresis-assisted epithelial-on corneal collagen cross-linking (i-CXL) with an accelerated irradiation protocol in young patients with progressive keratoconus (pKC), and to report outcomes and potential side effects at a 9-year follow-up.

The study was conducted at Salerno University Hospital, Salerno, Italy.

A cohort of 69 eyes from 56 patients (12–32 years) with progressive keratoconus (Kmax >1.5D, pachymetric thinning >20μm, or refractive progression >0.75D) over 6 months were enrolled. Patients underwent i-CXL with an accelerated protocol between January 11 and December 31, 2015, at the University Hospital of Salerno. The epithelial-on procedure used riboflavin (0.1% Ricrolin Plus®) via iontophoresis for 5 minutes, followed by UV-A irradiation at 370 nm and 10 mW/cm² for 9 minutes. Clinical and tomographic evaluations occurred at 1, 3, 6 months, then biannually up to 9 years. Endothelial cell count and macular OCT were performed at 3, 12 months, and annually.

The mean Kmax values showed a progressive decrease from baseline at various time points: -0.56D ± 0.81 at 3 months, -0.63D ± 0.89 at 6 months, and -1.02D ± 1.07 at 9 years, with statistically significant improvements starting from 6 months post-treatment (p<0.05). No significant changes were observed in pachymetry, endothelial cell count, intraocular pressure, or OCT parameters (foveal thickness and morphology) throughout the study period. Four eyes (6.6%) required retreatment with i-CXL, which resulted in stabilization of corneal parameters. No haze or other side effects were observed in the cohort.

Accelerated i-CXL with an epithelial-on approach demonstrated long-term efficacy in halting the progression of pKC in pediatric and young adult patients, with sustained improvements in Kmax and visual acuity over a 9-year period. The procedure was well-tolerated, with no significant side effects, and provided a favorable risk-benefit profile. The reduced invasiveness and short execution time make this technique particularly suitable for young patients, overcoming the challenges associated with traditional CXL methods that involve epithelial debridement.