Nano-structured glaucoma drainage implant safely and significantly reduces intraocular pressure in rabbits via post-operative outflow modulation

Kunal S Parikh,Laura M Ensign,Ju Young Ahn,Youlim Ha,Justin Hanes,Aditya Josyula,Ian Pitha,Revaz Omiadze

doi:10.1038/s41598-020-69687-4

Kunal S Parikh, Laura M Ensign + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-69687-4

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Abstract

Glaucoma is a leading cause of irreversible vision loss predicted to affect more than 100 million people by 2040. Intraocular pressure (IOP) reduction prevents development of glaucoma and vision loss from glaucoma. Glaucoma surgeries reduce IOP by facilitating aqueous humor outflow through a vent fashioned from the wall of the eye (trabeculectomy) or a glaucoma drainage implant (GDI), but surgeries lose efficacy overtime, and the five-year failure rates for trabeculectomy and tube shunts are 25–45%. The majority of surgical failures occur due to fibrosis around the vent. Alternatively, surgical procedures can shunt aqueous humor too well, leading to hypotony. Electrospinning is an appealing manufacturing platform for GDIs, as it allows for incorporation of biocompatible polymers into nano- or micro-fibers that can be configured into devices of myriad combinations of dimensions and conformations. Here, small-lumen, nano-structured glaucoma shunts were manufactured with or without a degradable inner core designed to modulate aqueous humor outflow to provide immediate IOP reduction, prevent post-operative hypotony, and potentially offer significant, long-term IOP reduction. Nano-structured shunts were durable, leak-proof, and demonstrated biocompatibility and patency in rabbit eyes. Importantly, both designs prevented hypotony and significantly reduced IOP for 27 days in normotensive rabbits, demonstrating potential for clinical utility.

Highlights

Glaucoma is a leading cause of irreversible vision loss predicted to affect more than 100 million people by 2040
Through variation of shunt diameter with flow rate held constant at 150 μL h−1, simulations revealed that a cylindrical shunt with inner diameter (ID) ≥ 100 μm will lead to hypotony at any physiologically relevant shunt length (Fig. 1A)
Through variation of shunt length with ID held constant at 50 μm, our simulation confirmed that a 6 mm long shunt is likely to avoid Intraocular pressure (IOP) associated with hypotony, even if aqueous humor flow rate were to fall below its physiological average of 150 μL h−1 (Fig. 1B)

Summary

Introduction

Glaucoma is a leading cause of irreversible vision loss predicted to affect more than 100 million people by 2040. Fluid flow through the venting region of a trabeculectomy is regulated by the tension created by sutures that secure a flap of scleral tissue This process leads to inconsistent outcomes, as sutures often need to be cut in the postoperative period due to inadequate IOP reduction, and the frequency of post-operative hypotony can exceed 10%10,11. In order to avoid hypotony in the immediate post-operative period, the tube is occluded or tied off for the initial 4–6 postoperative weeks to allow capsule formation[13] This strategy either allows for no IOP reduction in the immediate post-operative period or requires the surgeon to create venting incisions in the tube that can lead to inconsistent outcomes[14,15]. More recent evolutions of GDIs, minimally invasive glaucoma surgery (MIGS) devices, standardize venting IOP and reduce the risk of post-operative hypotony by utilizing dimensions modeled by the Hagen-Poiseuille equation (HPE): 8μLQ

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