Topo-Pachimetric Accelerated Epi-On Cross-Linking Compared to the Dresden Protocol Using Riboflavin with Vitamin E TPGS: Results of a 2-Year Randomized Study

Abstract

In the present study (clinical trial registration number: NCT05019768), we compared the clinical outcome of corneal cross-linking with either the standard Dresden (sCXL) or the accelerated custom-fast (aCFXL) ultraviolet A irradiation protocol using riboflavin–D-α-tocopheryl poly(ethylene glycol)-1000 succinate for progressive keratoconus. Fifty-four eyes of forty-one patients were randomized to either of the two CXL protocols and checked before treatment and at the 2-year follow-up. The sCXL group was subjected to CXL with 30 min of pre-soaking and 3 mW/cm2 UVA irradiation for 30 min. The aCFXL group was subjected to CXL with 10 min of pre-soaking and UVA irradiation of 1.8 ± 0.9 mW/cm2 for 10 min ± 1.5 min. In both groups, a solution of riboflavin–vitamin E TPGS was used. Uncorrected distance visual acuity, corrected distance visual acuity, pachymetry, Scheimpflug tomography, and corneal hysteresis were performed at baseline and after 24 months. Both groups showed a statistically significant improvement in corrected distance visual acuity, and keratometric and corneal hysteresis compared to baseline conditions; no statistically significant differences in outcomes between the two groups were observed. Improvement in refractive, topographic, and biomechanical parameters were observed after sCXL and aCFXL, making the riboflavin–VE-TPGS solution an effective option as a permeation enhancer in CXL procedures. Deeper stromal penetration of riboflavin could be complemented by photo-protection against UVA and free radicals formed during photoinduced processes.

Comparison of topographic outcomes between HPMC based and vitamin E TPGS based riboflavin solutions after corneal cross-linking

“…In a recent study, corneal cross-linking for progressive keratoconus was compared to ultraviolet A irradiation using the conventional Dresden or accelerated specialized fast (aCFXL) protocols. 18 As a result of this study, improvement was observed in biomechanical, topographic, and refractive characteristics following both procedures, and no statistical difference was found between the efficacies.…”

Recent advances in medicinal compounds related to corneal crosslinking

“…Ostacolo et al (2013) proved that VE-TPGS increased corneal penetration of riboflavin and corneal stiffness in transepithelial CXL on porcine corneas. They further confirmed the effectiveness of VE-TPGS to promote the permeation of riboflavin both in standard and accelerated CXL on KCN patients (Caruso et al, 2021). In a 24-month trial, VE-TPGS contributed to better clinical outcomes in transepithelial CXL with modified UVA irradiation (Caruso et al, 2016).…”

Vitamin E TPGS-Based Nanomedicine, Nanotheranostics, and Targeted Drug Delivery: Past, Present, and Future

“…After sCXL and aCFXL, refractive, topographic, and biomechanical parameters all improved, showing the riboflavin-TPGS solution as a viable alternative as a permeation enhancer in CXL treatments. Riboflavin may provide further photo-protection by neutralizing ROS and UVA radiation produced by photo-induced activities, allowing it to penetrate deeper into the stroma [ 135 ].…”