MIGS in 2020: Reviewing the Devices and Techniques

Glaucoma refers to a number of conditions that have, in common, characteristic optic neuropathy leading to reduced vision and potentially, blindness. Treatment of glaucoma consists of reducing intraocular pressure (IOP) using medical, laser or surgical therapy. Most glaucoma within our community is considered mild to moderate, based on the severity of damage to the optic nerve and/ or effect on the visual field.

When assessing risk benefit in patients with mild to moderate glaucoma, it can be hard to justify performing trabeculectomy or other traditional filtration surgery because of the associated risk

First line therapy for glaucoma is usually medical or laser therapy as these have the best safety profile. In mild to moderate glaucoma, the patient may be either asymptomatic or have only mild symptoms so it’s important that the treatment is not worse than the condition itself. After all, the aim of treatment is to maximise the patient quality of life, not cause it to decline.

Patients receiving medical and/or laser therapy for their mild to moderate glaucoma may fall into one of a number of categories including: i) well controlled and well tolerated, ii) well controlled but not well tolerated, iii) poorly controlled yet well tolerated, and iv) poorly controlled and poorly tolerated. It is our hope that all our patients fall into category i, but the sad reality is that many fall within groups ii to iv. These represent a failure of treatment, either because the glaucoma is not being slowed or stopped, or because the sideeffects from treatment are diminishing quality of life more than glaucoma itself.

Traditionally, the next treatment step for patients in categories ii to iv has been trabeculectomy. Trabeculectomy effectively lowers IOP but is also associated with significant and potentially sight threatening complications such as hypotony and endophthalmitis. When assessing risk benefit in patients with mild to moderate glaucoma, it can be hard to justify performing trabeculectomy or other traditional filtration surgery because of the associated risk. In the past, this has created a treatment gap, with a need for an IOP lowering treatment other than medication and/or laser that is safer than trabeculectomy or other traditional filtration surgery. This gap has recently been filled by minimally (micro) invasive glaucoma surgery (MIGS).

MIGS DEFINITION CHANGES OVER TIME

The term MIGS is attributed to Dr Ike Ahmed (Canada) in 2009 and was associated with defining features of a glaucoma surgical intervention that consisted of the following qualities:

1. Performed via an ab internomicro-incision,
2. Causes minimal trauma to normalocular anatomy,
3. Should have at least modest efficacyin lowering IOP,
4. Avoids complications inherent withother types of glaucoma surgery, and
5. Facilitates a rapid recovery from surgery.

The first generation of devices could more or less be described in these terms but over time, with the addition of new devices and the advent of new mechanisms of IOP reduction, there has been less and less adherence to this definition. As such, the term MIGS is now applied to a heterogenous group of IOP-lowering devices or techniques that act via different mechanisms, requiring different surgical techniques and with different recovery and safety profiles. For this reason, the term MIGS is no longer a useful descriptor, and it is better to think in terms of individual devices and where they may be of use in glaucoma management. For the purpose of this overview, I’ve grouped treatments below in terms of how they lower IOP.

TRABECULAR BYPASS DEVICES

These devices lower IOP by facilitating the flow of aqueous across the TM, into Schlemm’s canal and away via collector channels. They achieve this by either creating a direct connection between the anterior chamber and Schlemm’s canal, opening a previously closed or narrow Schlemm’s canal, or both. As they use and enhance existing aqueous outflow mechanisms, they generally perform well in terms of safety profile and speed of recovery

istent and istent Inject 

The istent (Figure 1A) and istent inject (Figure 1B) are both trabecular bypass stents with a number of design features that differentiate the two. Both are made from heparin-coated titanium and aim to provide a pathway for aqueous to flow from the anterior chamber into Schlemm’s canal without having to pass through the TM. The istent, launched in Australia in 2014, is a singular snorkel-shaped stent that measures 1 x 3mm. The istent inject, a further evolution of this technology, became available in 2016 and employs a smaller rivet-shaped design measuring 0.4mm (the smallest implantable device currently used in humans). As two stents are preloaded on a mechanised injector system, it allows the surgeon to target more of the TM and outflow channels compared to the singular first generation istent.

A prospective randomised clinical trial,1 of istent combined with cataract surgery verses cataract surgery alone in eyes with mild to moderate glaucoma, showed the istent offered additional benefits in terms of IOP reduction and reduced medication dependence. Twelve months after surgery, eyes that received a single istent had an increased chance of reaching an unmedicated IOP < 21mmHg (72% vs 50%) with a greater mean reduction in medications (1.4 vs 1.0) at the same time point.

The benefit of the istent inject has been evaluated in an identically designed study.2 With two years follow-up reported, eyes that received 2x istent inject were more likely to achieve an IOP <21mmHg (75.8% v 61.9%) with a greater mean reduction in medications (1.2 vs 0.8) at the same time point. Australian surgeons have reported similarly beneficial results in a broader range of glaucoma types.³

Hydrus 

The Hydrus (Figure 1C), made of nitinol (nickel-coated alloy), also traverses the TM and aims to allow aqueous to pass directly from the anterior chamber into Schlemm’s canal. Additionally, it tries to act as a scaffold to hold Schlemm’s canal open. It is much larger than the istent systems, measuring 8mm in length. Its size is thought to be an advantage in terms of directing aqueous to a longer segment of Schlemm’s canal and potentially more collector channels.

the term MIGS is now applied to a heterogenous group of IOP-lowering devices or techniques that act via different mechanisms, requiring different surgical techniques and with different recovery and safety profiles

A randomised trial of Hydrus combined with cataract surgery4 has shown some benefits in terms of IOP lowering and reduced medication dependence. Baseline IOP was 18.9mmHg and 18.6mmHg for each group respectively. At 24 months, both groups had a mean IOP of between 16–17mmHg but medication reduction was greater in the Hydrus group (2.0 down to 0.5) compared to cataract alone (2.0 down to 1.0). Mean washed out IOP, after 24 months, showed a significantly greater reduction in the Hydrus plus cataract group (26.3 mmHg to 16.2 mmHg) compared to cataract alone (26.6 mmHg to 19.6 mmHg).

SCHLEMM’S CANAL DILATING DEVICES

Ab Interno Canaloplasty (ABiC) 

Unlike the above mentioned trabecular bypass devices, ABiC (Figure 1D) does not involve the implantation of a stent, but rather the use of viscoelastic to dilate open Schlemm’s canal. First, a fibre-optic catheter enters Schlemm’s canal via an abinterno approach and traverses it through 360o to ensure patency of the entire system. Then, as the fibre-optic is slowly withdrawn, boluses of viscoelastic are injected to dilate Schlemm’s canal.

ABiC is essentially a modification of an older ab externo technique, but with the advantages of an ab interno approach including minimal tissue disruption and potentially quicker recovery. Ab externo canaloplasty has been shown to lower IOP and medication use in well-designed studies, including randomised clinical trials. It is reasonable to expect ABiC could achieve similar results but the clinical data at this stage is not as robust as ab externo canaloplasty and not to the level of some other devices/techniques described here. A recent meta-analysis of MIGS,⁵ was not able to identify any suitable studies for inclusion on ABiC. Since then, a number of case series have reported both IOP lowering and medication lowering in open angle glaucoma. However, what is lacking is large scale and/or prospective clinical studies.

TRABECULAR ABLATION DEVICES

These devices work on the premise that the TM is the main site of aqueous outflow resistance. By removing it, one removes this resistance and allows aqueous to flow directly into collector channels.

Trabectome 

Available since 2005, the Trabectome (Figure 1E) is an electrocautery device that burns, ablates and aspirates the TM using an ab interno approach via a clear corneal incision. The end result is a ‘de-roofed’ Schlemm’s canal that exposes collector channels directly to the anterior chamber. Surgeons aim to remove up to 180o of meshwork via a single incision. It may be performed as a stand-alone treatment or combined with other procedures such as cataract surgery.

A meta-analysis of Trabectome6 did not identify any randomised clinical trials on this technique but did report on the outcome of five prospective and two retrospective studies of stand-alone trabectome and seven prospective and three retrospective studies of trabectome combined with phacoemulsification. The mean weighted IOP reduction to final follow-up across studies was 9.77mmHg and 6.04mmHg for stand-alone and combined with phacoemulsification respectively. Eyes achieved these pressure reductions on 0.76 – 0.99 fewer medications.

Since the meta-analysis of Kaplowitz et al, a study comparing phacoemulsification combined with trabectome against phacoemulsification with istent for open-angle glaucoma has been reported.⁷ This study found little difference in IOP reduction following either intervention (-24% vs -22%, p = 0.331) but found both the early and late complication rate to be significantly higher in eyes treated with trabectome. Complications observed after trabectome, but not istent, included uveitis, hyphaema and cystoid macula oedema.

Kahook Dual Blade 

The Kahook Dual Blade (KDB; Figure 1F) performs an excisional goniotomy via an ab interno approach through a clear corneal incision. The instrument has a pointed distal tip that pierces the TM and enters Schlemm’s canal and, as it is advanced along the trajectory of the canal, lifts and stretches the TM up the instrument’s ramp and onto two parallel blades that excise a narrow strip of TM. Unlike a standard goniotomy knife that simply incises the TM, leaving contiguous anterior and posterior flaps, the KDB excises a strip of TM, leaving a direct opening for aqueous to pass from the anterior chamber into Schlemm’s canal. The KDB has the advantage of being a stand-alone instrument that does not require a power source – ideal for low resource settings.

While there are reports for outcomes beyond two years for treatments such as istent, Hydrus and Cypass, significant gaps in our knowledge of long term efficacy and safety remain

Clinical data on the efficacy and safety of the KDB is limited to a number of retrospective studies with six to 12 months follow-up.⁸ Of note, there has been no prospective randomised clinical trial to date. These studies suggest IOP lowering and medication reduction after surgery, as either stand-alone treatment or combined with phacoemulsification, is roughly in line with outcomes reported following trabecular bypass devices or trabecular ablation.

SUB-CONJUNCTIVAL DEVICES

The objective of these devices is to shunt aqueous from the anterior chamber into the sub-conjunctival space, to bypass conventional outflow. They are blebdependent procedures that in some respects work in the same way as a trabeculectomy but aim to address some of the problems with trabeculectomy including long surgery time, prolonged recovery and complications. Although discussed under the term MIGS, they do not adhere to the original definition described above in the same way that trabecular ablation devices do. They still require manipulation and/or disruption of conjunctiva, they don’t necessarily avoid complications seen with other glaucoma procedures, and recovery may still be prolonged. So in this respect, they are more of an alternative to trabeculectomy rather than a surgical step that bridges the gap between medication and/or laser and traditional glaucoma surgery methods.

XEN 

The XEN45 glaucoma implant (Figure 1J) is a 6mm long hydrophilic cross-linked porcine gelatin stent with a 45 micron lumen. It comes pre-loaded on an injector and is designed to be inserted via an abinterno approach through the irido-corneal angle and into the sub-conjunctival space. When positioned correctly, the proximal end sits within the anterior chamber and the distal end in the sub-conjunctival space. It facilitates flow of aqueous from the anterior chamber to sub-conjunctival space and formation of a bleb. Modulation of wound healing is needed to ensure optimal bleb function, so the surgery is often combined with the use of an antimetabolite such as mitomycin C.

It therefore has a number of features in common with trabeculectomy, including anti-metabolite use and formation of a sub-conjunctival bleb. It differs in that it requires the implantation of a device, it can be performed ab-internally, and the surgical time is generally quicker.

To date, there have been no prospective randomised clinical trials published in the literature to report the efficacy and safety of the XEN45 for management of glaucoma. Having said that, there is still a substantial and growing body of literature relating to this device. Most notable among these is the APEX study,⁹ which aimed to evaluate the utility of the XEN45 in open angle glaucoma in a prospective non-randomised open label design. With two years of followup reported, they found in eyes that had XEN combined with phacoemulsification, IOP reduced from 20.6mmHg to 14.3mmHg and in eyes with XEN alone, IOP reduced from 22.1mmHg to 14.4mmHg. Similarly, medications reduced in both groups; 2.5 to 1 in the combined XEN with phacoemulsification group and 2.7 to 1.2 in the XEN only group.

The need for careful post-operative management and reported complications has not been dissimilar to that associated with trabeculectomy. For example, the bleb needling rate following XEN45 in the APEX study was approximately 40%. Reports have emerged in the literature of hypotony, XEN45 erosion, blebitis and endophthalmitis, all of which are vision threatening complications. A retrospective analysis of outcomes from a centre in Germany, published this year,¹⁰ suggests that while the safety of XEN45 and trabeculectomy are similar, trabeculectomy efficacy is superior. So while the literature shows that XEN45 lowers IOP and medication dependence in open angle glaucoma, it has not addressed two of the key features of MIGS; i.e. to provide a treatment that is safer and has more rapid recovery compared to traditional glaucoma surgery.

PreserFlo Microshunt 

Unlike all other devices and techniques described here, the PreserFlo (Figure 1G) is designed for insertion via an ab externo approach after the conjunctiva is retracted and the sub-tenon’s space and sclera are exposed. The PreserFlo is an 8.5mm-long (outer diameter 350μm; internal lumen diameter 70μm) device made from a highly biocompatible and bioinert material called poly (styreneblock- isobutylene-block-styrene), or SIBS. It is inserted through a channel created by passing a needle through the scleral wall into the anterior chamber. Once in place, it facilitates the flow of aqueous from anterior chamber to a subconjunctival bleb. As with XEN45 and trabeculectomy, it is a bleb-dependent procedure and as such, is used in combination with anti-metabolite application such as mitomycin C.

Trabecular bypass devices are most closely aligned with the original concept of MIGS and have a robust evidence base

Although it received CE mark approval in 2012, it still remains in its infancy in terms of clinical data. A randomised clinical trial comparing PreserFlo to trabeculectomy began recruiting in 2013 and is due to report outcomes this year. Non-controlled studies point to the potential benefits of this surgery with one reporting a mean IOP reduction from 23.8mmHg to 10.7mmHg after three years follow-up, and medication reduction from 2.4 to 0.7 over the same time period.¹¹

It remains to be seen how PreserFlo compares to trabeculectomy, but it seems likely that the type and severity of glaucoma that will benefit from this surgery will be different to that which benefits from other procedures discussed here.

SUPRACHOROIDAL DEVICES

Suprachoroidal devices aim to lower IOP by shunting aqueous into a newly created space between scleral and choroidal layers – the suprachoroidal space. The concept originates from observations that eyes that have a cyclo-dialysis cleft (communication between anterior chamber and suprachoroidal space), either from trauma or surgery, may have chronically low IOP. Devices are placed between the scleral spur and choroid via an ab interno approach and slide easily into place with little or no resistance. Among all techniques described here, these devices are technically one of the easiest for a surgeon to use.

Cypass 

The Cypass microstent (Figure 1H) is a 6.35mm long stent made from polyamide that consists of a central lumen, side ports and proximal retention rings. It is supplied preloaded on an inserter that approaches the iridocorneal angle via a clear corneal incision. It has been used as a standalone treatment or in combination with phacoemulsification.

The COMPASS study¹² was a randomised clinical trial that assessed the safety and efficacy of Cypass in combination with cataract surgery. The eyes in which the Cypass was implanted had a significantly greater IOP reduction (24.4mmHg to 17mmHg) compared to cataract surgery alone (24.5mmHg to 19.1mmHg). Similarly, medication reduction after two years was also greater in the Cypass group (1.4 to 0.2) whereas cataract surgery only was associated with a lesser reduction for the same period (1.3 to 0.6).

In August 2018, Cypass was voluntarily withdrawn from clinical use because data from COMPASS-XT (a five year extension of the original COMPASS study) found significantly higher rates of corneal endothelial cell loss in eyes that had received a Cypass.

iStent Supra 

Although the overall concept is identical to Cypass, it is hoped the iStent Supra (Figure 1I) is sufficiently different in design to overcome the concern regarding corneal endothelial health and suprachoroidal stents. It is shorter, curved rather than straight, and made of different material (polyethersulfone and titanium). There is no clinical data yet available on its safety and efficacy but there has been one report, with positive results, of its use in combination with two istents for refractory glaucoma.¹³

CYCLOABLATION

Cycloablative procedures have traditionally been used as a last option in the glaucoma treatment pathway and in particular for eyes that have poor visual potential and/ or are painful. However, recent updates to techniques have allowed surgeons to use cycloablative treatments earlier and with a greater safety profile. Two methods are worthy of discussion in the context of MIGS.

Endoscopic Cyclodiode Photocoagulation 

Diode laser is applied to the ciliary body under direct visualisation via a clear corneal or pars plana approach. It can only be used in eyes that are pseudophakic or aphakic, as there is a need for space in the posterior chamber to fit the probe. It is, therefore, unsuitable as a stand-alone treatment in phakic eyes. Despite being available since the mid-1990s, endoscopic cyclodiode photocoagulation (Figure 1K) has never been assessed in a randomised clinical trial. There are several large case series¹⁴ that suggest it lowers IOP and medication dependence, but the evidence in support of its utility and safety is not as strong as many of the other techniques discussed here. It is particularly helpful in the management of plateau iris syndrome as endoscopic cyclodiode photocoagulation causes shrinkage and posterior rotation of the ciliary body, which in turn drags open the irido-corneal angle.

Micropulse Cyclodiode 

This is a newer method (Figure 1L) of application of traditional trans-scleral cyclodiode. Rather than using ‘spot’ treatments, it uses continuous application of lower power laser that aims to achieve IOP lowering without the post-operative inflammation and pain associated with the original technique. It has even been used in combination with cataract surgery.

There haven’t been any prospective randomised trials of micropulse cyclodiode and of the small number of case series to date, most report treatment outcomes for eyes with refractory glaucoma. One series from the USA¹⁵ did examine the outcome in eyes with good central vision. With 12 months follow-up, mean IOP reduced from 25.69mmHg to 15.45mmHg. Over the same period, mean number of medications reduced from 3.51 to 2.67. Mean acuity dropped slightly, from LogMAR 0.16to 0.22, but significantly, 20% of eyes lost greater than two lines of vision and cataract progression was noted in 40% of phakic eyes.

CONCLUSION

There are now many devices and techniques that are considered under the umbrella term ‘MIGS’. Review of their mechanism of action and the evidence in support of their efficacy and safety shows they comprise a heterogenous group of treatments. Trabecular bypass devices are most closely aligned with the original concept of MIGS and have a robust evidence base. In contrast, subconjunctival devices have more in common with trabeculectomy and as such, are likely to be suited to a different group of patients with more advanced or complex glaucoma. Schlemm’s canal dilation or ablation treatments show promise, but more evidence is needed, and the same is true of the newer cyclo-destructive techniques. The lesson learned from the withdrawal of Cypass is that long term follow-up of each of these devices and techniques is important. While there are reports for outcomes beyond two years for treatments such as istent, Hydrus and Cypass, significant gaps in our knowledge of long term efficacy and safety remain.

To earn your CPD points from this article visit mieducation.com/MIGS-in-2020-reviewing-thedevices- and-techniques 

Dr Colin Clement is a Sydney based ophthalmologist who specialises in the management of cataract and glaucoma. He is one of Australia’s leading experts on MIGS, having completed fellowship training in the United Kingdom and Switzerland. He currently coordinates the MIGS wet lab training course at Sydney Eye Hospital, has lectured on MIGS both in Australia and internationally, and is an investigator and advisory board member for a number of MIGS treatments. He consults privately at Eye Associates, Fairfield Eye Surgery and North Shore Eye Centre in Sydney, New South Wales. 

References 

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2. Samuelson TW et al. Prospective, Randomized, Controlled Pivotal Trial of iStent inject Trabecular Micro-Bypass in Primary Open-Angle Glaucoma and Cataract: Two-Year Results. Ophthalmology 2019;126:811–821. 
3. Clement CI et al. One-year outcomes following implantation of second-generation trabecular micro-bypass stents in conjunction with cataract surgery for various types of glaucoma or ocular hypertension: multi-centre, multi-surgeon study. Clinical Ophthalmology. 2019 13: 491-499 
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5. Lavia C et al Minimally-invasive glaucoma surgeries (MIGS) for open angle glaucoma: A systematic review and metaanalysis. PLoS One. 2017 Aug 29;12(8) 
6. Kaplowitz K, et al. Review and meta-analysis of abinterno trabeculectomy outcomes. Br J Ophthalmol 2016;100:594–600 
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8.El Mallah M et al 12-Month Retrospective Comparison of Kahook Dual Blade Excisional Goniotomy with Istent Trabecular Bypass Device Implantation in Glaucomatous Eyes at the Time of Cataract Surgery. Adv Ther. 2019; 36(9): 2515–2527. 

9. Reitsamer et al. Two-year results of a multicenter study of the ab interno gelatin implant in medically uncontrolled primary open-angle glaucoma. Graefe’s Archive for Clinical and Experimental Ophthalmology (2019) 257:983–996 
10. Wagner et al Efficacy and Safety of XEN®-Implantation vs. Trabeculectomy: Data of a “Real-World” Setting PLoS One 2020 Apr 20;15(4):e0231614. 
11. Sadruddin et al Ab externo implantation of the MicroShunt, a poly (styrene-block-isobutylene-block-styrene) surgical device for the treatment of primary open-angle glaucoma: a review Eye Vis (Lond). 2019; 6: 36. 
12. Vold S et al. Two-Year COMPASS Trial Results: Supraciliary Microstenting with Phacoemulsification in Patients with Open-Angle Glaucoma and Cataracts. Ophthalmology 2016;123:2103–2112. 
13. Myer JS et al. Prospective Evaluation of Two iStent ® Trabecular Stents, One iStent Supra Suprachoroidal Stent, and Postoperative Prostaglandin in Refractory Glaucoma: 4-year Outcomes Advances in Therapy 2018 Mar;35(3):395-407 
14. Clement CI et al. Combining phacoemulsification with endoscopic cyclophotocoagulation to manage cataract and glaucoma. Clin Exp Ophthalmol. 2013;41(6):546–551 
15. Varikuti V et al. Outcomes of Micropulse Transscleral Cyclophotocoagulation in Eyes With Good Central Vision Journal of Glaucoma: October 2019 – Volume 28 – Issue 10 – p 901-905