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Evan D. Schoenberg, Diane A. Blake, F. Beau Swann, Andrew W. Parlin, David Zurakowski, Curtis E. Margo, Thiruselvam Ponnusamy, Vijay T. John, Ramesh S. Ayyala; Effect of Two Novel Sustained-Release Drug Delivery Systems on Bleb Fibrosis: An In Vivo Glaucoma Drainage Device Study in a Rabbit Model. Trans. Vis. Sci. Tech. 2015;4(3):4. doi: https://doi.org/10.1167/tvst.4.3.4.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate two drug delivery systems, a nonbiodegradable poly(2-hydroxyethyl methacrylate) (P[HEMA]) system with mitomycin C (MMC) and a biodegradable poly(lactic-co-glycolic acid) (PLGA) system with 5-fluorouracil (5-FU) with and without MMC for their ability to reduce fibrosis when attached to an Ahmed glaucoma valve (AGV) and implanted in a rabbit model.
New Zealand albino rabbits (48) were divided into six equal groups, and AGVs, modified as described below, were implanted in the right eye of each rabbit. The groups included (1) PLGA alone; (2) P(HEMA) plus MMC (6.5 μg); (3) PLGA plus 5-FU (0.45 mg); (4) PLGA plus 5-FU (1.35 mg); (5) PLGA plus 5-FU and MMC (0.45 mg and 0.65 μg, respectively); (6) PLGA plus 5-FU and MMC (1.35 mg and 0.65 μg, respectively). The rabbits were followed for 3 months prior to euthanasia.
The bleb wall thickness was significantly less in groups 2, 5, and 6 compared to the rest. At 3 months, the PLGA polymer had completely disappeared, while the P(HEMA) polymer remained intact. There were no statistical differences in the degree of clinically graded conjunctival injection, histologic inflammation, or histologic fibrosis among the six groups.
We successfully created a sustained-release drug delivery system that decreased the postoperative fibrosis using both a nonbiodegradable P(HEMA) polymer and a biodegradable (PLGA) polymer. Both systems appear to work equally well with no side effects.
These results are supportive of the antifibrotic effect of the slow-release drug delivery system following glaucoma drainage device implantation, thus paving the way for human pilot studies.
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