Abstract
Purpose :
Excessive fibrosis is the major cause for the failure of surgical glaucoma drainage device (GDD) implantation. Sustained mitomycin C (MMC) released approaches are promising to help reduce the scar formation. Opal shale (OS) with special characteristics has the potential to be a drug delivery carrier. This study tested the hypothesis that an innovative GDD coated with MMC-loaded OS microparticles (MPs) can reduce the excessive postoperative fibrosis.
Methods :
Improved GDDs were designed with MMC-loaded OS MPs physically absorbed on the Ahmed glaucoma valve surface. In vitro, the novel GDD was observed by scanning electron microscopy (SEM) to reveal surface morphology. The release kinetics of MMC were explored using ultraviolet spectrophotometer. Primary human tenon’s fibroblasts (HTFs) and rabbit tenon’s fibroblasts (RTFs) were used to test the biocompatibility and inhibitory of the drug-loaded OS MPs. New Zealand rabbits were divided into three equal groups (n=6/group) for in vivo study. GDD with MMC-OS MPs coating, blank OS MPs coating and normal GDD were implanted in rabbit eyes. Intraocular pressure and bleb morphology were assessed for up to 12 weeks. The pathology of the blebs was observed after euthanasia.
Results :
Natural OS MPs successfully attached to the entire GDD surface. 5.45 ± 0.08 μg of MMC was loaded and released in vitro over 90 hours. MMC-loaded OS MPs were able to inhibit fibroblasts proliferation with low toxicity in vitro. In vivo study, IOP was significantly lower in MMC-OS MPs group compared with drug-free groups (P<0.05). Bleb wall thickness in the MMC-OS MPs group of 0.46 ± 0.03 mm was less extensive than in the blank OS MPs and normal GDD groups of 0.63 ± 0.007 mm and 0.61 ± 0.03mm (P<0.05). The pathological examination showed the collagen layer of roof and baseline sides were thinner in the MMC-OS MPs group than in the other two groups at 12 weeks postoperation (P<0.05). There were no statistical differences in the degree of histologic inflammation or histologic fibrosis among the two control groups.
Conclusions :
We presented an innovative and improved GDD coated with OS MPs, which were loaded with MMC. The results are consistent with our hypothesis that the ameliorated drainage device was well tolerated and effective in reducing the fibrous reaction in vivo.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.