Understanding and optimizing the influence of glaucoma drainage implant surface architecture and design to prevent post-operative fibrosis

NIH RePORTER · NIH · R01 · $478,872 · view on reporter.nih.gov ↗

Abstract

PROJECT SUMMARY Glaucoma is a leading cause of irreversible blindness globally. Trabeculectomy and glaucoma drainage implant (GDI) procedures are potentially curative, but reserved for advanced cases due to the rate of complications and failure. In the immediate post-operative period, fluid venting is regulated either by ad hoc surgical interventions devised by the surgeon or by valves that do not perform as expected as much as 16% of the time. This process leads to inconsistent outcomes, including hypotony, which can exceed 10%. Studies report 5-year failure rates of 30% and 50% and reoperation rates of 30% and 9% in patients who had trabeculectomy and GDI surgery, respectively. The majority of surgical failures occur due to fibrotic encapsulation. Complications and surgical failures burden the healthcare system through non-reimbursed post-operative visits and costly re-operations, and lead to poor patient outcomes and disease progression. Minimally Invasive Glaucoma Surgery devices were designed to address these limitations; however, in clinical practice, these devices have greater than 20% rates of both reoperation and failure, and due to their static design, do not enable optimal intraocular pressure (IOP) reduction through all phases of the post-operative period. An ideal GDI would (1) reduce operative time and skill through facile, standardized implantation eliminating the need for ad hoc interventions, (2) prevent post-operative complications including hypotony and implant migration, and (3) achieve significant, long-term IOP reduction by modulating fibrosis, thereby, improving visual outcomes and reducing the burden on healthcare systems. We describe a novel, highly versatile manufacturing platform capable of fabricating implants with a wide range of compositions and architectures. This platform will enable rigorous evaluation and understanding of the effects of implant design and topography on the foreign body and fibrotic responses that undermine GDI efficacy. We previously manufactured small-lumen, nano-structured stents that were durable, leak-proof, and demonstrated biocompatibility, patency, and IOP-lowering in rabbit eyes. We hypothesize that rationally designed, nano- structured GDIs will reduce fibrosis and increase fluid conductivity by providing cues that enable cellular integration and inhibit pro-fibrotic signaling pathways to suppress scar formation. When combined with a novel partially degradable shunt design, these properties may eliminate hypotony, reduce complications, and lead to long-term IOP reduction to significantly improve outcomes for the most vulnerable glaucoma patients.

Key facts

NIH application ID
10776721
Project number
1R01EY035669-01
Recipient
JOHNS HOPKINS UNIVERSITY
Principal Investigator
Kunal Sailesh Parikh
Activity code
R01
Funding institute
NIH
Fiscal year
2024
Award amount
$478,872
Award type
1
Project period
2024-03-01 → 2024-08-01