Enhanced Riboflavin Stromal Delivery Using Microchannel-Assisted Iontophoresis for Corneal Crosslinking.

Purpose: The purpose of this study was to determine if iontophoresis of riboflavin (Rf) combined with femtosecond generated epithelial microchannels (MCs) could shorten the time required for Rf stromal delivery and subsequent crosslinking (CXL).

Methods: Eighty-four ex vivo rabbit eyes were divided into three groups: group 1 = iontophoresis alone; group 2 = iontophoresis with MC; and group 3 = MC alone. Iontophoresis was performed using a small electric current with varying current and time. MCs were generated using a 1030 nm femtosecond (FS) laser to machine the corneal epithelial surface in a 6 mm diameter region. Ex vivo eyes were treated with topical iso-osmolar Rf solution, and stromal Rf concentration was determined spectrophotometrically by eluting Rf from trephined stromal buttons. In vivo, six rabbits underwent iontophoresis or iontophoresis + MC followed by ultraviolet-A crosslinking (UVA CXL) and imaged for collagen autofluorescence (CAF) signal to determine CXL efficacy.

Results: Ex vivo iontophoresis achieved a threefold increase in stromal Rf concentration when combined with MC for 5 to 10 minutes (equivalent to MC alone for 30 minutes compared to iontophoresis alone). In vivo, iontophoresis + MC resulted in a significantly higher (4-fold) CAF intensity than iontophoresis alone.

Conclusions: MCs and low current iontophoresis produce a significantly higher stromal Rf concentration than iontophoresis alone and equivalent to MC alone at greatly reduced Rf treatment time. Additionally, the combined treatment results in a four-fold increase in CAF intensity over iontophoresis alone.

Translational relevance: A combined treatment of iontophoresis and MC significantly enhances stromal Rf concentration resulting in increased CXL while significantly reducing procedure time.