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.
