Abstract
Abstract: :
Purpose:The ability of an episcleral implant at the equator of the eye to deliver drugs to the posterior segment was evaluated using a sustained–release implant containing gadolinium–DTPA (Gd–DTPA), and the real–time movement of this drug surrogate was assessed using magnetic resonance imaging (MRI) in the rabbit eye. The results were compared with a similar implant placed in the vitreous cavity through a scleral incision at the equator. Methods:Polymer–based implants releasing Gd–DTPA were manufactured, in vitro release rates determined, and placed in the subconjunctival space on the episclera or in the vitreous cavity in live rabbit eyes (in vivo) and in enucleated eyes (ex vivo). Dynamic MRI was performed using a 4.7 Tesla MRI system for 8–hours. MRI images were developed and analyzed with Matlab and ImageJ software. Results:In vitro release rates showed the Gd–DTPA released from the implants followed first–order kinetics over an 8–hour period. The in vivo eyes with episcleral implants delivered a mean total of 3 micrograms of Gd–DTPA in the vitreous and clearance appeared to be predominantly anterior. No Gd–DTPA signal was detected in the posterior segment of the eye. In the ex vivo eyes, Gd–DTPA signal was present throughout the vitreous and posterior segment with a mean total of 24 micrograms present in the vitreous. In the in vivo eyes with intravitreal implants, a concentration gradient of Gd–DTPA was present in the vitreous cavity with lower levels present at the vitreoretinal interface suggesting a trans–retinal elimination mechanism. This concentration gradient was abolished in the ex vivo eyes. Conclusions:In vivo, episcleral implants at the equator of the eye did not deliver a significant amount of Gd–DTPA into the vitreous and no signal was present in the posterior segment. An 8–fold increase in vitreous Gd–DTPA concentration occurred in the enucleated eyes suggesting that there are significant barriers to the movement of drugs from the episcleral space into the vitreous in vivo. Real–time MRI using Gd–DTPA, and potentially metal ion/ drug complexes, may be useful in understanding the spatial relationships of ocular drug distribution and clearance mechanisms in the eye.
Keywords: imaging/image analysis: non–clinical • computational modeling