Primary open-angle glaucoma (POAG) has a prevalence in the US of 2% of adults over 40 years old, or about 2.2 million people, and is expected to increase to 3.3 million in 2020 as the population ages (1). POAG is a chronic, progressive optic neuropathy in adults in which there is a characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons. It is associated with an increased intraocular pressure (IOP), due to a buildup of aqueous fluid within the eye which can lead to visual field loss and optic nerve damage, usually without any associated pain or discomfort. The increased IOP is secondary to an imbalance between aqueous fluid secretion and fluid outflow despite an open angle. Nearly 40% of those with otherwise characteristic POAG may not have elevated IOP measurements (1).
In the primary (conventional) outflow pathway from the eye, aqueous humor passes through the trabecular meshwork, enters a space lined with endothelial cells (Schlemm canal), drains into collector channels, and then into the aqueous veins. Increases in resistance in the trabecular meshwork or the inner wall of the Schlemm canal can disrupt the balance of aqueous humor inflow and outflow, resulting in an increase in IOP and glaucoma risk.
The goal in POAG is to reduce the IOP to slow the development of optic nerve damage. The IOP can be reduced by medical treatment or surgery, alone or in combination. IOP above 21 mmHg has been shown to increase rates of visual field loss. However, because of the differences in susceptibility to pressure-related disc damage among POAG patients, pressure-lowering treatments are aimed at achieving a lower “target” pressure individualized to each patient’s baseline IOP in which glaucomatous damage occurred.
When the maximum tolerated medical therapy fails to control progression of glaucomatous optic neuropathy, surgical care is considered the next treatment option. Traditional filtration surgery includes trabeculectomy (including ExPress shunt) and aqueous drainage implants (Ahmed, Baerveldt, Molteno). Trabeculectomy uses the patient’s own sclera to create a fistula to the subconjunctival space over the sclera superiorly. Aqueous drainage implants use silicone/plastic tubing and large plates to shunt aqueous to the subconjunctival space in the equatorial region of the eyeball.
While IOP outcomes are generally worse with aqueous drainage implants compared with trabeculectomy, complications such as hypotony (low pressure), and postoperative infection are reduced. However, failure rates are similar (approximately 10% of devices fail annually), and shunts still have complications, including corneal endothelial failure and erosion of the overlying conjunctiva.
The term micro-invasive or minimally invasive glaucoma surgery (MIGS) refers to a group of newer surgical procedures that are performed by using an ab interno (from inside the eye) approach via gonioscopic guidance and involve minimal trauma to ocular tissues. In contrast to external filtration surgeries such as trabeculectomy and aqueous tube shunt, these procedures are categorized as internal filtration surgeries. Compared with traditional filtration surgery, MIGS holds the promise of faster recovery time and less severe complications.
It is this potentially improved safety profile that opened up the indications for MIGS to include patients with early-stage glaucoma to reduce the burden of medications and problems with compliance (due to eye drop application difficulty, cost, cosmetic effects, and frequency). Another area of investigation is patients with glaucoma who require cataract surgery. An advantage of ab interno shunts is that they may be inserted into the same incision and at the same time as cataract surgery. In addition, most devices do not preclude subsequent trabeculectomy if needed. Therefore, health outcomes of interest are the IOP achieved, reduction in medication use, ability to convert to trabeculectomy, complications, and device durability.
There are five FDA approved/cleared micro-invasive surgical stents, the iStent Trabecular Micro-Bypass Stent (2011), the CyPass Micro-Stent System (July, 2016), the XEN Glaucoma Treatment System (Nov., 2016), the Hydrus Microstent (Aug., 2018), and the iStent inject (Jun, 2018). The iStent is a small (1 mm x 0.5 mm) L-shaped titanium device that is inserted into Schlemm’s canal to augment the natural outflow system. The iStent inject system comprises 2 heparin-coated titanium stents (each having 0.23 mm diameter x 0.36 mm height, 0.08 mm central lumen diameter, and four 0.05 mm side outlets to allow for multidirectional outflow), both inserted into Schlemm’s canal using a pre-loaded auto-injection trocar. Hydrus is a 8 mm nitinol, crescent-shaped microstent with alternating spines for support and windows to provide outflow, also placed into Schlemm’s canal. CyPass is a 6.35 mm long fenestrated microstent made of biocompatible polyimide inserted into the supraciliary space, thus using an alternative outflow system. The XEN45 is a 6 mm long porcine-derived gelatin stent inserted into the subconjunctival space, bypassing the natural outflow system.
iStent, iStent inject, Hydrus and CyPass were FDA approved (Cypass recalled by FDA for safety concerns Sept., 2018) for use in combination with cataract surgery to reduce IOP in adults with mild or moderate OAG and a cataract that are currently being treated with medication to reduce IOP. XEN45 was granted FDA clearance for the management of refractory glaucoma, including cases where previous surgical treatment has failed, cases of primary open angle glaucoma, and pseudoexfoliative or pigmentary glaucoma with open angles that are unresponsive to maximum tolerated medical therapy. The published pivotal trial data for each, constituting the main evidentiary support, is summarized in the attached table. MIGS Pivotal Trials
