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Effect of 2 Novel Sustained-release Drug Release Systems on Bleb Fibrosis

An In Vivo Trabeculectomy Study in a Rabbit Model

Swann, Forrest B., MD*; Singh, Sujata, MD*; Blake, Diane, PhD*,†; John, Vijay, PhD; Le, Crystal, MD*; Fullerton, Mitchell, BS*; Margo, Curtis, MD§; Zhang, Ze, MD; Muddasani, Nishika, MD*; Wall, Jennifer, MD*; Satija, Celine, MD*; Greenberg, Erin, MD§; Mancera, Norberto, MD§; Zurakowski, David, PhD; Ayyala, Ramesh S., MD, FRCS§

doi: 10.1097/IJG.0000000000001215
Original Studies
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Precis: Rabbit model studies suggested better morphology blebs with equal intraocular pressure (IOP) efficacy as a standard mitomycin C (MMC) trabeculectomy using a novel slow-release drug delivery antifibrotic system delivering small quantities of MMC and 5-fluorouracil (5-FU).

Purpose: To evaluate 2 different concentrations of biodegradable poly(lactic-co-glycolic acid) (PLGA) system with 5-FU and MMC (ElutiGLASS) for their ability to reduce fibrosis and compare the results with standard trabeculectomy with MMC in a rabbit model.

Materials and Methods: New Zealand albino rabbits (19) were divided into 3 groups (A, B, C) and standard trabeculectomy operation was performed in the right eye of each rabbit.

Group (A) had trabeculectomy with MMC (0.4 mg/mL) applied using a Weck cell sponge; (B) trabeculectomy with slow-release ElutiGLASS (0.23 mg, 5-FU/0.33 μg MMC released over 23 to 30 d); (C) trabeculectomy with rapid release ElutiGLASS (0.45 mg of 5-FU/0.65 μg MMC, released over 5 to 7 d). The rabbits were followed for 3 months before euthanasia.

Results: Bleb morphology, vascularity, and fibrosis were less pronounced in groups B and C when compared with group A at 3 months. Group B appears to have a lower and more diffuse bleb appearance compared with the other 2 groups with honeycomb appearance on both clinical examination and ultrasound biomicroscopy imaging with higher percentage of maintained bleb space (83%), less fibrosis than group A while maintaining the same low inflammation score as the other 2 groups on histology. At 3 months, the PLGA polymer had completely disappeared in all rabbits. There were no statistical differences in the degree of IOP reduction or histologic inflammation, among the 3 groups.

Conclusions: We successfully created a sustained-release antifibrotic drug delivery system that delivered known dosage of the drugs at doses that are significantly lower than the current standard, and resulted in less fibrosis while maintaining a healthy bleb and equal reduction of IOP.

Translational Relevance: These results are supportive of the antifibrotic effect of the slow-release drug delivery system used in conjunction with trabeculectomy, thus paving the way for human pilot studies to improve and simplify existing surgical techniques for filtering surgeries in glaucoma.

Departments of *Ophthalmology

Biochemistry and Molecular Biology, Tulane University School of Medicine

Department of Chemical and Biomolecular Engineering

Tulane University, New Orleans, LA

Departments of Anesthesia and Surgery, Harvard Medical School, Boston, MA

§Department of Ophthalmology, University of South Florida, Tampa, FL

Disclosure: D.B. (P); V.J. (P); R.S.A. (P, R, I). The remaining authors declare no conflict of interest.

Reprints: Ramesh S. Ayyala, MD, FRCS, 12901 Bruce B Downs Blvd, MDC 21, Tampa, FL 33612 (e-mail: rayyala@health.usf.edu.edu).

Received November 19, 2018

Accepted January 21, 2019

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