Minimally Invasive Glaucoma Surgery: New Devices and Future DirectionsAuthors:Iqbal (Ike) K. Ahmed, MD, FRCSCFaculty and DisclosuresCME Released: 3/20/2017

Valid for credit through: 3/20/2018

Introduction

Glaucoma is the leading cause of irreversible blindness worldwide, and open-angle glaucoma (OAG) is the most common form, affecting an estimated 3 million people in North America.[1] Glaucoma is most effectively treated by lowering the intraocular pressure (IOP) in the affected eye, and minimally invasive glaucoma surgery (MIGS) has been gaining traction as a safe and effective treatment approach for OAG with or without cataract surgery.[2,3] Medscape spoke with Dr Ike Ahmed, Assistant Professor at the University of Toronto in Canada, about how MIGS procedures and innovative implant devices are helping to stave off advanced disease for patients with mild-to-moderate OAG.

Medscape: What is MIGS and how does it differ from trabeculectomy and glaucoma drainage devices (GDDs)?

Dr Ike Ahmed: Trabeculectomy and GDDs have been around for a long time and have a high degree of potency to lower IOP.[4] The downside is that these incisional procedures are associated with short- and long-term complications, including treatment failure due to scarring, decreased quality of life due to bleb-related foreign body sensation, induced astigmatism, secondary cataracts, and vision-threatening complications such as blebitis, endophthalmitis, or choroidal hemorrhage.[4] Patients and physicians alike are reluctant to rush into these surgeries; therefore, these traditional approaches tend to be reserved to treat advanced progressive or late-stage disease. Although medications can be effective, adverse events, ocular toxicity, and patient-related factors frequently lead to nonadherence, which has been reported to be as high as 60%.[5] This nonadherence causes disease progression and eventually necessitates surgery to treat more severe glaucoma.

MIGSs are a group of new microincisionalsurgical interventions that can be used earlier in the treatment paradigm. Because MIGS spares collective tissue damage, these procedures are associated with greater safety profiles.[3,5,6] Most MIGS procedures use an ab interno approach through clear corneal incisions, which we know are very effective for cataract surgery.[7] The ab interno approach is more efficient than that of trabeculectomy and GDDs, which involve external dissections. In addition, ophthalmologists tend to be familiar with clear corneal incisions, which increases the likelihood of proper wound construction and decreases the likelihood of postoperative inflammation.

Medscape: What are the differences between the MIGS approaches and the implanted devices used?

Dr Ahmed: The best way to look at the different MIGS approaches is from where the excess aqueous fluid drains (Table 1): increasing trabecular outflow by targeting the Schlemm's canal, increasing uveoscleral outflow via suprachoroidal pathways (eg, supraciliary stenting), or creating subconjunctival drainage pathways. The Schlemm's canal and suprachoroidal pathways are internal drainage procedures and referred to as "iMIGS," while subconjunctival "MIGS Plus" procedures are typically more efficacious, but require some postoperative bleb management.

Table 1. MIGS Approaches and Implant Devices

Device: Manufacturer: Materials/ Description: Procedure: FDA approval
Increasing Trabecular Outflow
Hydrus™ Microstent[5,8] Ivantis Inc., Irvine, 
California 8.0 mm, crescent shaped stent made 
of nitinol (alloy of nickel and titanium) Implanted ab interno as trabecular 
bypass and Schlemm's canal scaffold Investigational use only in
United States
iStent® 
Inject[3,5-6] Glaukos Corporation,
Laguna Hills, California Second-generation of iStent® comes 
preloaded with 2 bullet-shaped stents Implanted ab interno into the Schlemm's 
canal Investigational use only in
United States
iStent® Trabecular
Micro-Bypass Stent[5,9,10] Glaukos Corporation, 
Laguna Hills, California Heparin-coated nonferromagnetic 
grade 5 titanium stent; 60 µg weight, 
1.00 mm length, 0.33 mm height; 
L-shaped Implanted ab interno into the Schlemm's 
canal 2012
Trabectome®[5,11] NeoMedix, Tustin, 
California   Ab interno trabeculectomy: a strip of TM 
and the inner wall of Schlemm's canal are 
removed to create an outflow pathway 2006
Increasing Uveoscleral Outflow
CyPass® Micro-Stent [2,5,14] Alcon Laboratories, Inc.,
Forth Worth, Texas Fenestrated polyamide tube; 
6.35 mm length Implanted ab interno between the ciliary 
body and sclera 2016
iStent Supra®[3,13] Glaukos Corporation, 
Laguna Hills, California Polyethersulfone and titanium; 
4.0 mm tube Implanted ab interno between the ciliary
body and sclera Investigational use only in
the United States
SOLX® Gold Micro 
Shunt[12] SOLX Corp, Waltham, 
Massachusetts 24-karat gold, flat, nonvalved plate; 
5.2 mm length, 3.2 mm width Implanted ab externo transscleral 
approach Investigational use only in
the United States
STARflo™[13] iSTAR Medical SA, 
Isnes, Belgium Silicone microporous material; 11 × 5 mm,
anvil-shaped shunt Implanted ab externo into 
suprachoroidal space via a scleral flap Investigational use only in 
the United States
Targeting the Subconjunctival Space
InnFocus 
Microshunt®[15,16] Santen Pharmaceutical Co., Ltd, 
Osaka, Japan Polystyrene-block-isobutylene-block-
styrene biostable thermoplastic 
elastomer Implanted ab externo to facilitate 
subconjunctival filtration; mimics 
trabeculectomy Investigational use only in United States
XEN® Glaucoma 
Treatment System[5,17] AqueSys, Inc., Aliso
Viejo, California Collagen-derived gelatin cross-linked 
with glutaraldehyde; 6.0 mm; 
cylindrical (XEN45 Gel Stent) 
and injector Implanted ab interno allowing drainage
between the anterior chamber and the 
subconjunctival space 2016

FDA = US Food and Drug Administration; TM = trabecular meshwork.

Increasing Trabecular Outflow

The MIGS procedures targeting the Schlemm's canal include trabecular meshwork (TM) cutting (goniotomy/trabeculotomy) and microstenting. Canal-targeting procedures are the safest of all the MIGS procedures; however, surgeons need to be comfortable with the anatomy before implanting stenting devices. The iStent® Trabecular Micro-Bypass Stent (Glaukos Corporation, Laguna Hills, California) is inserted through the TM into the Schlemm's canal.[18,19] In 2012, the iStent became the first US Food and Drug Administration (FDA)-approved MIGS device, and a recent literature review concluded that iStent implantation with phacoemulsification resulted in a significantly lower, long-term decrease in IOP and number of medications used compared with phacoemulsification alone, with no major complications.[20] Canal-targeting procedures have a floor limitation, the episcleral venous pressure, that ultimately limits the degree of IOP reduction.[18] However, the placement of multiple stents has been shown to increase the ability to further lower IOP, and devices that contain multiple stents (eg, iStent Inject [Glaukos Corporation, Laguna Hills, California]) are under study.[5]

The Hydrus™ Microstent (Ivantis Inc., Irvine, California) is an intracanalicular scaffold inserted into Schlemm's canal to maintain patency and establish outflow, allowing aqueous fluid to access multiple collector channels. In a European study of 100 patients with OAG and cataract, IOP was significantly lower at 2 years in the stent plus cataract surgery group compared with the cataract surgery alone group, with no differences in safety.[8] In the United States, the ongoing HYDRUS IV clinical trial with patients with mild-to-moderate glaucoma undergoing cataract surgery is the largest MIGS study to date.[21]

Increasing Uveoscleral Outflow

Supraciliary stenting creates a conduit for aqueous fluid to exit the anterior chamber across the anterior ciliary muscle to the suprachoroidal space, which then dissipates via nearby vasculature or by reaching the episclera through scleral pores. This approach has the potential for lowering IOP more than procedures that target drainage to the canal because it doesn't have the same floor limitation. On the other hand, this type of stenting has demonstrated more variability in IOP obtained depending on how patients respond to surgery. Variations in healing around the device in the supraciliary space predict how well the IOP will go down. If the patient heals quickly, then the pressure may not drop as low.[22]

The CyPass® Micro-Stent (Alcon Laboratories, Inc., Fort Worth, Texas) was approved by the FDA in 2016.[14] It creates an alternative drainage pathway by creating a controlled cyclodialysis with stented outflow to the supraciliary space.[5] The procedure is straightforward, as the stenting technique is easily adaptable and less challenging. The CyPass Micro-Stent has been studied in more than 1000 patients worldwide, and the benefits include potential continuous control of IOP, reduced or eliminated need for glaucoma medications, and preserved conjunctival and scleral tissue. For example, the COMPASS study of approximately 500 patients with mild-to-moderate OAG who underwent phacoemulsification, the cohort with the CyPass stent demonstrated a safe and sustained 2-year reduction in IOP and glaucoma medication use.[23]

Creating Subconjunctival Drainage Pathways

Finally, subconjunctival procedures are the most potent of all the MIGS procedures. These procedures use microstenting to prevent hypotony and control flow into a bleb, which is managed postoperatively.[5] The pathway used is similar to that of trabeculectomy and tube shunt procedures. Mitomycin C is typically used when performing subconjunctival procedures, as it helps control wound healing and prevent subconjunctival fibrosis and encapsulation. In 2016, the FDA approved the XEN® Glaucoma Treatment System (AqueSys Inc.) using a including a stent made out of a soft, collagen-derived gelatin that is known to be noninflammatory.[17] After implantation with an injector, the device swells, which prevents it from migrating.[5]

Another device under investigation is the InnFocus MicroShunt® (Santen Pharmaceutical Co., Ltd, Osaka, Japan), a microtube that shunts aqueous humor from the anterior chamber of the eye to a flap formed under the conjunctiva and Tenon's capsule.[16] This product uses a biomaterial called poly(styrene-block-isobutylene-block-styrene), which is an ultrastable biomaterial with virtually no foreign body reaction in the body, which minimizes inflammation and capsule formation in the eye.[16] This shunt is implanted via an ab externo approach vs the ab interno approach usually associated with MIGS; however, it does not require dissection of the sclera.[16] A study of 23 patients with Microshunt placement with or without cataract surgery showed that more than 95% had sustained "qualified success" (defined as an IOP ≤14 mmHg and IOP reduction ≥20%). Currently, the InnFocus Microshunt is in the final phase of a study that compares the implanted device with trabeculectomy.[24]

Medscape: Which patients would be considered good candidates for MIGS?

Dr Ahmed: I think physicians will need to keep 3 questions in mind: Firstly, does the patient need a glaucoma procedure? Secondly, if so, what would be the most effective aqueous outflow pathway based on patient target pressure and risk profile? Thirdly, within each of the pathways, which is the optimal device?

Canal stents have been around longer and afford the highest degree of safety, while supraciliary stents are more recent and have the potential to lower IOP. If we are aiming for a very low target pressure, that patient would typically be a candidate for the more potent subconjunctival pathway procedure. On the other hand, the MIGSs that target the canal and the suprachoroidal space approaches are more appropriate for patients earlier in the disease stage who don't necessarily require very low target pressure, patients who are going into cataract surgery for whom safety is a concern, or patients who need to reduce or discontinue their glaucoma medications.

What percentage of your patients with mild-to-moderate open-angle glaucoma (OAG) would you consider a candidate for minimally invasive glaucoma surgery (MIGS)?

Your Peers Chose:

1 to 10%

39%

11 to 25%

35%

26 to 50%

16%

Over 50%

10%

Medscape: To conclude, what are some of the challenges clinicians face when considering MIGS for their patients?

Dr Ahmed: Because these procedures are so new, clinicians are still trying to figure out where they fit in the treatment paradigm. I think the biggest consideration is determining the most appropriate approach for each patient.

When it comes to cataract surgery, safety is paramount, since a longer recovery may lead to more unstable vision.[25] In my opinion, if you can perform MIGS safely, any opportunity to perform glaucoma surgery with cataract surgery is a great opportunity since we may only get one shot. It's a different story with patients with cataracts who have borderline high IOP. In these scenarios, it's more of a question of whether they actually need the glaucoma surgery. If these patients are taking IOP-lowering eye drops and there is a greater likelihood of getting them off their medications by performing a MIGS procedure with the cataract surgery, then I would consider it. Having patients on less medication means we can worry less about the issues of adherence, which we know is common and ultimately leads to fluctuations in pressure, which can cause complications.

Then there are patients without cataracts, but their IOP isn't as well-controlled with medication. Do these patients need surgery? Their IOPs aren't as low as we would like for them to be, but not so high that we would expose them to the risks associated with trabeculectomy. If we choose to watch and wait, there is the chance their disease will progress. These are the patients I typically see. Again, this is when MIGS allows us to intervene earlier with more confidence that we aren't going to expose the patient to potentially serious complications from traditional surgery.