Faculty Collaboration Database

Effect of 2 Novel Sustained-release Drug Release Systems on Bleb Fibrosis: An In Vivo Trabeculectomy Study in a Rabbit Model. J Glaucoma 2019 Jun;28(6):512-518

Date

02/27/2019

Pubmed ID

30807440

DOI

10.1097/IJG.0000000000001215

Scopus ID

2-s2.0-85062387118 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

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.

Author List

Swann FB, Singh S, Blake D, John V, Le C, Fullerton M, Margo C, Zhang Z, Muddasani N, Wall J, Satija C, Greenberg E, Mancera N, Zurakowski D, Ayyala RS

MESH terms used to index this publication - Major topics in bold

Absorbable Implants
Animals
Drug Delivery Systems
Drug Implants
Drug Liberation
Endophthalmitis
Fibrosis
Filtering Surgery
Fluorouracil
Glaucoma
Humans
Intraocular Pressure
Male
Mitomycin
Postoperative Complications
Rabbits
Tonometry, Ocular
Trabeculectomy