MRI study of subconjunctival and intravitreal injections

Abstract

Previous magnetic resonance imaging (MRI) studies to investigate the routes of penetration and barriers in ocular delivery have provided insights into the mechanisms of transscleral and intraocular drug delivery. The objective of the present study was to investigate ocular penetration and clearance after subconjunctival and intravitreal injections using a contrast agent at concentrations higher than those in the previous studies. This high concentration approach was hypothesized to allow the visualization of the contrast agent in the eye that could not be achieved previously. Subconjunctival and intravitreal injections of contrast agent Magnevist, a model hydrophililc probe, were performed in rabbits, and the distribution and clearance of the probe after the injections were examined by MRI. After subconjunctival injection in vivo, significant contrast agent penetration into the anterior chamber was observed but not into the vitreous. A clearance pathway of the hydrophilic probe from the subconjunctival depot to the regions near the periocular fat behind the eye was found. After intravitreal injection in vivo, the contrast agent was observed in the anterior chamber, optic nerve, and tissues surrounding the eye during clearance. MRI continues to provide insights into the transport barriers and clearance pathways of hydrophilic molecules in ocular delivery.

Figure 1

Ratios of MR signals of Gd–DTPA solutions to that of saline as a function of Gd–DTPA concentration obtained with the 3-T MRI scanner. Symbols, experimental data; curve, best-fit line for the data using Eqs. 1-3.

Figure 2

Representative MR images (coronal view) of the high concentration Gd–DTPA vials in saline, illustrating the effects of magnetic susceptibility artifact at (a) 0.05 M, (b) 0.1 M, and (c) 0.2 M Gd–DTPA. (d) Diagram illustrating the vials.

Figure 3

MR images (axial view) of the eye before contrast agent injections (the controls) using MR sequence (a) with and (b) without fat suppression.

Figure 4

Representative MR images of rabbit eyes after subconjunctival injections of Gd–DTPA at concentrations of (a) 0.05 M, and (b and c) 0.5 M in vivo. Images were acquired during the 16 min MR scans of (a) 27–43 min, (b) 10–26 min, and (c) 49–65 min after the injections. From left to right, axial image slices at different positions from the front to the back of the head.

Figure 5

Representative MR images of rabbit eyes after subconjunctival injections of Gd–DTPA at concentration of 0.5 M postmortem. Images were acquired during the 16 min MR scan of 35–51 min after the injection. From left to right, axial image slices at different positions from the front to the back of the head.

Figure 6

Representative MR images in the intravitreal injection studies of Gd–DTPA at concentrations of (a) 0.005 M, (b) 0.05 M, and (c and d) 0.5 M in vivo, acquired at (a, b, and c) 4 h and (d) 12 h after the injections. From left to right, axial image slices at different positions from the front to the back of the head.