Analysis of Subconjunctival and Intrascleral Drug Delivery Using Magnetic Resonance Imaging

Abstract

Purpose: : To evaluate the delivery of drugs to the retina from subconjunctival and intrascleral infusions by using contrast–enhanced T₁–weighted magnetic resonance imaging.

Methods: : Gd–DTPA was infused into the right eye of Dutch Belted rabbits by using a 24 G angiocath tube inserted either subconjunctival or intrascleral. Five millimeters of the angiocath tubing was advanced nasally at a distance of 5 mm from the limbus in the superonasal quadrant. The angiocath was connected to a syringe pump located outside the scan room using PE–10 tubing prefilled with 0.005 M Gd–DTPA. Infusions at 10 µl/min were performed for one hour and scans acquired every 3.5 minutes.

Results: : In T₁–weighted images acquired during Gd–DTPA infusion the conjunctiva, sclera and retina appeared bright while the choroid appeared dark. The retina could be distinguished from the sclera and conjunctiva by the dark choroid that separated the two bright tissue layers. High signal intensity was present in the retina immediately after the start of intrascleral infusion. After 17.5 minutes of intrascleral infusion, Gd–DTPA in the retina was seen to reach the optic nerve. No signal was present in the retina during subconjunctival infusion throughout an infusion time of 1 hour.

Conclusions: : High signal intensity appeared in the retina during intrascleral infusions while no signal was present in the retina during subconjunctival infusions. These results suggest that there are clearance mechanisms and/or transport barriers present during subconjunctival delivery that are either absent or are reduced during intrascleral delivery.

Keywords: imaging/image analysis: non-clinical