Abstract
Purpose :
To determine whether pulsed high-intensity ultrasound combined with microbubbles can promote permeation of topical compounds into the corneal stroma.
Methods :
Fresh cadaveric rabbit eyes with intact corneal epithelium were placed in a solution of 0.1% riboflavin and microbubbles. Treated eyes received pulsed ultrasound at either 1.0 or 3.5 MPa (1.07 MHz, 5% duty cycle) applied to the central cornea for 3 or 6 minutes, and the eyes were then left in riboflavin solution for a total immersion time of 20 minutes. Control eyes without ultrasound treatment received the same exposure to riboflavin solution with microbubbles. Corneas were then excised, and confocal microscopy was performed to detect the presence of riboflavin in the cornea.
Results :
At a corneal depth of 200 microns, the average fluorescence intensity of riboflavin in the groups treated with 3.5 MPa for 6 minutes, 3.5 MPa for 3 minutes and 1.0 MPa for 6 minutes was respectively 4868 ± 728.7 A.U (n = 15), 2648 ± 268.4 A.U. (n=18), 2433 ± 445.5 A.U. (n=7). When compared to controls (269.7 A.U.; n=10) the difference was statistically significant (p-value <0.05), demonstrating approximately 9-18 fold therapeutic gain.
Conclusions :
Microbubble enhanced pulsed high-intensity ultrasound was very effective in delivering riboflavin into the corneal stroma despite the presence of a previously intact epithelial barrier. This approach may offer a means of achieving clinically useful concentrations of topically applied drugs in the corneal stroma without removing the corneal epithelium.
This is a 2020 ARVO Annual Meeting abstract.