Clinical Evaluation of Paclitaxel Drug Eluting Implant for the Treatment of Glaucoma in a Rabbit Model

Abstract

Purpose: : To examine the in-vivo biocompatibility of a drug eluting Glaucoma drainage device (GDD) MIDI-RX loaded with Paclitaxel for potential treatment of Glaucoma.

Methods: : The MIDI-RX implants composed of poly(styrene-b-isobutylene-b-styrene) (SIBS) microtube and plate were drug loaded by spotting solution of Paclitaxel and SIBS (2:1 wt) in THF on both sides of the plate. A study was conducted using a control (0ug), low (20-30ug), medium (60-70ug), and high (90-100ug) concentrations of Paclitaxel loaded on the MIDI-RX on 4 NZW rabbits. The surgery was performed under deep IM anesthesia: an incision was made, sub-conjunctival space was dissected, and a track was created utilizing a 27G needle ~ 2mm below the limbus, the tube of the GDD was placed in the anterior chamber, the plate was sutured to the sclera and covered with conjunctiva. The rabbits were examined at POD 1 and 3 by photo slit-lamp and at POD 7, 14, 21, 28, 35, and 42 under the operation microscope. Histological analysis was performed on all operated and control eyes.

Results: : The control MIDI-RX with no Paclitaxel had a thin capsule; a normal response seen in previous MIDI-Ray rabbit studies. The lowest dose MIDI-RX showed an avascular and fibrotic cystic bleb starting at POD 21. The medium and high dose MIDI-RX also had an avascular and fibrotic cystic bleb as well as thinning areas on the bleb at 3 and 4 weeks, and some neighboring conjunctival melting.

Conclusions: : This pilot study indicated that even the lowest dose of Paclitaxel tested was too strong to be used in the eye, suggesting the use of a much lower concentration or utilizing another milder drug.Support: Florida Lions Eye Bank; NIH - NEI SBIR grant (1R43EY018519-01A1); an unrestricted grant from Research to Prevent Blindness; Henri and Flore Lesieur Foundation (JMP).

Keywords: aqueous • trabecular meshwork • wound healing