Corneal permeability assay of topical eye drop solutions in rabbits by MRI

This study examined the corneal permeability of topical eye drop solutions added with various corneal penetrating accelerators and gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) by nuclear magnetic resonance imaging (MRI). Twenty-four New Zealand rabbits were randomly divided into 3 groups according to the random digits table: Gd-DTPA group, in which the rabbits received 23.45% Gd-DTPA; hyaluronic acid group, in which 23.45% Gd-DTPA plus 0.2% hyaluronic acid was administered; azone group, in which 23.45% Gd-DTPA with 0.2% azone was given. Fifty microliters of the eye drops was instilled into the conjunctive sac every 5 min, for a total of 6 applications in each group. Contrast medium signals in the cornea, anterior chamber, posterior chamber, and vitreous body were scanned successively by MRI. The morphology and cell density of the corneal endothelium were examined before and 24 h after the treatment. The results showed that the residence time of Gd-DTPA in the conjunctival sac in the hyaluronic acid and azone groups was longer than that in the Gd-DTPA group. The signals in the anterior chamber of the Gd-DTPA and hyaluronic acid groups were increased slightly, and those in the azone group strengthened sharply. The signal intensity continuously rose over 80 min before reaching plateau. The strengthening rate of signals in the anterior chamber was 19.63% in the Gd-DTPA group, 53.42% in the sodium hyaluronate group, and 226.94% in the azone group. No signal was detected in the posterior chamber or vitreous body in all the 3 groups. Corneal morphology and cell density did not show any significant changes after the treatment in all the 3 groups. It was concluded that azone can significantly improve the corneal permeability of drugs that are similar to Gd-DTPA in molecular weight and molecular size, and MRI is a noninvasive technique that can dynamically detect eye drop metabolism in real time.