Enhanced Riboflavin Stromal Delivery Using Microchannel-assisted Iontophoresis for Corneal Crosslinking (CXL)

Abstract

Purpose : Transepithelial Ultraviolet Corneal Crosslinking (TE UVA CXL) has been shown to mitigate some of the negative side effects of standard UVA CXL by avoiding epithelial debridement, although crosslinking is less effective due to the reduced Riboflavin (Rf) penetration into the stroma. While femtosecond (FS) based micro-machining to form epithelial microchannels (MC) can greatly improve Rf stromal penetration, this procedure still requires 30 minutes of Rf application to achieve maximum stromal delivery equivalent to 50% of that obtained with complete epithelial removal. The purpose of this study was to determine if iontophoresis of Rf combined with MC could both shorten the treatment time for MC and also improve Rf stromal delivery by iontophoresis.

Methods : Eighty-four ex vivo rabbit eyes were divided into three groups: G1, iontophoresis alone; G2, iontophoresis with MC; and G3, MC alone. Iontophoresis was performed using a small electric current (Iontofor-CXL, OPIA Technologies) to transport Rf into the stroma, varying both current and time. MCs were generated using a 1030 nm FS laser (Chameleon, Coherent Inc.) with 5μJ pulse energy to machine the corneal epithelial surface in a 6mm diameter region. All eyes were treated with topical iso-osmolar (300 mOsmol/l) Rf solution (1.0% riboflavin-5-phosphate in PBS), and stromal Rf concentration was determined spectrophotometrically by eluting Rf from 6 mm diameter stromal buttons placed in 1 ml of PBS overnight.

Results : Iontophoresis alone (G1, n = 31) achieved Rf stromal concentrations of 4.73 ± 0.82 ug/ml (1 mA for 10 min), 4.18 ± 0.42 ug/ml (1 mA for 5 min), and 3.65 ± 0.23 ug/ml (0.5 mA for 10 min) which were not significantly different. Using the same Iontophoresis exposures combined with MC (G2, n = 48) achieved significantly higher (P < 0.001*) Rf concentrations of 12.64 ± 1.82 ug/ml, 10.37 ± 2.28 ug/ml, and 12.8 ± 1.38 ug/ml respectively. Furthermore, Iontophoresis for 10 minutes at 0.5 or 1 mA achieved the same stromal concentration as MC alone with 30 minutes treatment.

Conclusions : A combined treatment of MCs and low current iontophoresis produces a significantly higher stromal Rf concentration than iontophoresis alone and equivalent to MC alone at a greatly reduced Rf treatment time.

Supported by: NIH EY024600, RPB 203478, Discovery Eye Foundation

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.