Controversies in the Use of MIGS

Minimally invasive glaucoma surgery (MIGS) has fulfilled an unmet need in the management of glaucoma. This chapter highlights some controversial issues regarding the use of MIGS in clinical practice, including (1) whether there is sufficient evidence to advocate combining MIGS with cataract surgery over cataract surgery alone, (2) the merits and drawbacks of different approaches to trabecular bypass and canal-based MIGS procedures, (3) the effect of MIGS on endothelial cell loss, (4) suprachoroidal MIGS devices and whether there is still a role for these procedures, and (5) a comparison between subconjunctival MIGS and trabeculectomy. Several questions are still left unanswered and hopefully, further research and more clinical experience with these new technologies will help improve surgical outcomes for patients.

Anatomy of the Aqueous Outflow Drainage Pathways

Lowering intraocular pressure (IOP) has been central to glaucoma care for over a century. Minimally invasive glaucoma surgical (MIGS) devices are able to exploit different aspects of aqueous outflow to reduce IOP. Increasing aqueous humour outflow may be achieved either through facilitating the existing pathways of Schlemm’s canal and the suprachoroidal space or to bypass the normal angle anatomy to create a full thickness fistula into the subconjunctival space. A complete understanding of angle anatomy and outflow pathways is important to develop new treatment strategies, improve current ones and better target the right operation for particular glaucoma subtypes.

Suprachoroidal MIGS Devices

The suprachoroidal outflow pathway has the potential to reduce intraocular pressure (IOP) significantly but has been associated with sight-threatening complications including severe and prolonged hypotony. Historically, suprachoroidal devices have been implanted ab externo requiring a conjunctival peritomy and scleral flap dissection. Additionally, the long-term efficacy of previous attempts to harness this space has been disappointing due to occlusion of implanted devices by fibrosis in the suprachoroidal space. More recently, there have been a number of suprachoroidal devices that are injected ab interno., including the CyPass Micro-Stent (Alcon Laboratories Inc., Fortworth, Texas, USA), the iStent Supra (Glaukos Corporation, San Clemente, CA, USA) and the MINIject (iSTAR Medical Isnes, Belgium). These have utilized a clear corneal entry, thereby sparing the conjunctiva. Early results with these ab-interno devices showed safety and efficacy in IOP-lowering that is similar to Schlemm’s canal minimally invasive glaucoma surgery devices and procedures. Despite the ab-interno approach, their long-term efficacy also seems to be limited by fibrosis. In addition, the first commercially available ab-interno suprachoroidal device, the CyPass Micro-Stent, has been voluntarily withdrawn globally by the manufacturer in August 2018, after 5-year follow-up data demonstrated a higher level of endothelial cell loss with the device than in controls. The iStent Supra and MINIject are not yet available commercially.

New Modalities of Cycloablation and High-Intensity-Focused Ultrasound

Cycloablative or cyclodestructive procedures aim to lower intraocular pressure (IOP) by decreasing the function of the ciliary body and thereby decreasing the rate of aqueous production. Cycloablative procedures were typically used in refractory glaucoma in eyes with poor visual potential; however, more focused energy and targeted destruction of the ciliary body have led to an increase in cyclodestructive treatment options that are now an important adjunct to our surgical armamentarium. This chapter highlights the history of these procedures while focusing on current modalities including transscleral diode cyclophotocoagulation (TSCPC), micropulse transscleral diode cyclophotocoagulation (MP-TSCPC, MicroPulse P3, IRIDEX IQ810 Laser System, Mountain View, CA, USA), and High-Intensity Focused Ultrasound (HIFU). Specifically, this chapter discusses the protocols, indications, results, and complications of each featured procedure.

Globalization of MIGS

Globalization is a comprehensive phenomenon with significant implications for global health. The globalization of minimally invasive glaucoma surgery (MIGS) is currently still a work in progress, with these devices slowly making inroads into Asia, Australasia, South America, and South Africa. Although MIGS companies can enjoy a quantum leap in economies of scale by serving global markets rather than only a confined domestic market, there are considerable economic, logistical, training, legal, and regulatory challenges that they need to overcome. The globalization of MIGS may benefit glaucoma patients worldwide, by reducing medication burden, improving the quality of life, and potentially decreasing the global incidence of glaucoma-related blindness.

XEN Gel Implant

Among all the novel glaucoma surgical devices, the XEN Gel Implant (Allergan plc, Dublin, Ireland) is the only one which uses an ab-interno approach to drain aqueous to the subconjunctival space, similar to conventional filtration surgery. Most MIGS procedures target the Schlemm’s canal and the collector channels which can be difficult to locate. The patency of the downstream drainage system cannot be accurately assessed and the episcleral venous pressure cannot be routinely measured, leading to unpredictable surgical outcomes for trabecular bypass surgery. In contrast, subconjunctival aqueous drainage is more effective at lowering the intraocular pressure, as is evidenced by the efficacy of trabeculectomy which has a long track record. The main advantages of the XEN Gel Implant over other filtering procedures include its less invasive surgical procedure and the favorable safety profile, fast visual recovery, and short surgery duration, rendering this implant particularly suited for patients who are unable to tolerate a long surgical duration or a delayed visual recovery. Although designed as a stand-alone procedure, XEN implantation can be combined with phacoemulsification in patients with concurrent cataract. Although its pressure-lowering ability appears to be superior to trabecular bypass and suprachoroidal MIGS devices, there are surgical nuances which can be difficult to master and the pre- and postoperative management is critical in the success of the XEN Glaucoma Treatment System.

Overview of MIGS

The term, minimally- or micro-invasive glaucoma surgery (MIGS), has entered common ophthalmic parlance and is playing an increasing role in the management of glaucoma patients. In common, the devices and procedures referred to are safer, less tissue invasive and associated with faster recovery than traditional filtering surgery, such as trabeculectomy or aqueous shunt implantation. MIGS can be categorized according to the tissue they target (or bypass): trabecular meshwork (TM) MIGS, subconjunctival MIGS, suprachoroidal MIGS and newer cycloablation procedures. A number of MIGS devices and techniques (e.g. TM MIGS) have relatively modest efficacy, but potential utility in a very large group of glaucoma patients with disease that is insufficiently severe to justify the invasiveness of conventional filtration surgery and the consequent intensity of postoperative care yet, burdened with medication and the attendant side effects and compliance issues thereof. On the other hand, subconjunctival MIGS devices, which are associated with bleb-related complications, can potentially achieve efficacy approaching that of traditional filtering surgery and are appropriate in selected individuals when larger IOP reductions are required, the exception being cases where glaucoma is very advanced. This book covers the techniques that are most commonly regarded as eligible to sit under the MIGS umbrella. Irrespective of the modest efficacy of many MIGS devices and techniques, the favourable safety profile lowers the threshold for early glaucoma surgery, especially when combined with cataract surgery, potentially delaying the requirement for more invasive surgery and associated risks.

iStent: Trabecular Micro-Bypass Stent

Within the class of procedures termed minimally invasive glaucoma surgery (MIGS), the iStent Trabecular Micro-Bypass Stent (Glaukos Corporation, San Clemente, CA, USA) is an intraocular implant that resides within Schlemm’s canal and allows for direct bypass of the trabecular meshwork by aqueous fluid. The acceptance of MIGS is growing due to its role in lowering intraocular pressure in mild-to-moderate glaucoma combined with its favorable safety profile. With transscleral glaucoma-filtering surgery, there is an increased potential for significant complications including hypotony, suprachoroidal hemorrhage, and long-term risk of endophthalmitis. By contrast, the iStent minimizes these risks and has demonstrated similarities to cataract surgery in terms of associated complications. Multiple publications have described both the safety and efficacy of the implant. These studies are reviewed in addition to a description of the implantation technique and postoperative management pearls. The second-generation model, the iStent inject, may ease implantation and the use of multiple stents may potentially play a role in more advanced disease.

PRESERFLO MicroShunt

The PRESERFLO® MicroShunt (Santen Pharmaceutical Co. Ltd., Osaka, Japan), formerly called the InnFocus MicroShunt®, is a trans-scleral device that shunts aqueous humour from the anterior chamber to a filtering bleb under the conjunctiva and Tenon’s capsule. Manufactured from an inert biocompatible material called poly(styrene-block-isobutylene-block-styrene), or ‘SIBS’, the device elicits minimal foreign body reaction and inflammation; potentially reducing the risk of bleb-related fibrosis and failure. The MicroShunt is 8.5 mm long with a 70 μm lumen and is designed to minimize hypotony based on the Hagen–Poiseuille equation. Inserted via an ab-externo approach, the MicroShunt eliminates the need for creation of a scleral flap, sclerostomy, iridectomy, scleral flap suturing and postoperative suture lysis. Clinical trials show promising results with the MicroShunt achieving intraocular pressure reduction approaching that of trabeculectomy, the current gold standard for treating refractory glaucoma.

Ab-Interno Trabeculotomy

The Trabectome (NeoMedix Corporation, San Juan Capistrano, CA, USA) is a US Food and Drug Administration—approved surgical device which removes a segment of the trabecular meshwork and the inner wall of the Schlemm’s canal using an ab-interno approach, enhancing aqueous outflow via increased access to the Schlemm’s canal and the collector channels. This is a bleb-less procedure which spares the conjunctiva, hence does not adversely affect the outcome of subsequent conventional glaucoma filtration surgeries. Multiple studies have shown that Trabectome surgery results in a reduction in IOP and the number of ocular hypotensive agents, though the efficacy is modest compared with conventional filtration surgery. The safety profile of Trabectome surgery is favorable compared with conventional glaucoma surgery, with the most common complication being intraoperative and postoperative bleeding. Additional research is required to understand how the efficacy of Trabectome surgery can be maximized.