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

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. Glaucoma is a disease of the optic nerve and a leading worldwide cause of irreversible vision loss. Over 60 million people were affected by glaucoma in 2010, and more than 12 million will be bilaterally blind due to glaucoma by 2020. Glaucoma will affect more than 110 million individuals by 2040 1,2. Intraocular pressure (IOP) reduction prevents glaucoma progression and vision loss 3,4. Clinically, ophthalmologists use a variety of approaches to lower IOP, including medications, laser procedures, and/or incisional surgeries. Topical medications are first-line therapy in most cases as they reduce IOP while avoiding complications such as bleeding, infection, and hypotony that can reduce vision and are associated with incisional surgeries. However, topical medications do not always

Animal Model Contributions to Primary Congenital Glaucoma

“…The inflammation of Ex-PRESS filtering was milder than that of trabeculectomy. Furthermore, nanostructured glaucoma drainage implants have also been successful in rabbit models, showing good tolerance, minimal leakage of implants, good compatibility with cells and tissues, and IOP reduction by 33–44% [ 123 ]. These studies suggest that the rabbit model is ideal for simulating surgical treatment.…”

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“…Similarly, ocular inserts that are placed into the conjunctival sac can provide prolonged release of drugs [43][44][45]. An alternative are implantable nano-drainage systems, that pro- vide a bypass route for aqueous humor outflow [46,47].…”

In Situ Gelling Electrospun Ocular Films Sustain the Intraocular Pressure-Lowering Effect of Timolol Maleate: In Vitro, Ex Vivo, and Pharmacodynamic Assessment

“…Glaucoma is a disease associated with limited drainage of the aqueous humor and increased intraocular pressure (IOP), which subsequently leads to progressive damage to the optical nerve and permanent loss of vision. , It affects more than 60 million individuals worldwide with a chance of reaching over 110 million by 2040 . Treatment of glaucoma is mainly based on topical drug administration aiming at IOP reduction, by enhancing aqueous humor drainage or by reducing aqueous humor production .…”

“…Glaucoma is a disease associated with limited drainage of the aqueous humor and increased intraocular pressure (IOP), which subsequently leads to progressive damage to the optical nerve and permanent loss of vision. , It affects more than 60 million individuals worldwide with a chance of reaching over 110 million by 2040 . Treatment of glaucoma is mainly based on topical drug administration aiming at IOP reduction, by enhancing aqueous humor drainage or by reducing aqueous humor production . Although most ophthalmic formulations are in the form of eye drops, major issues have been reported and are mainly associated with poor drug bioavailability in the target tissue (less than 5%), due to nasolacrimal drainage into the systemic circulation, rapid tear turnover, and consequently, short ocular residence time (1–3 min) .…”

“…Several attempts have been made for the ocular delivery of antiglaucoma drugs using contact lenses, nanoliposomes, and self-assembling peptides, also employing electrospinning to fabricate draining implants, , coat soft contact lenses, or control the delivery of therapeutic agents. , Other groups have produced electrospun nanofibers to improve the ocular delivery of anti-inflammatory ,,, and antimicrobial agents ,, for the treatment of common infections and medical conditions of the eye.…”