Source: Healio Interviews
Disclosures: Ahmed reports he is a consultant for Aerie Pharmaceuticals, Alcon, Allergan, Ellex, ELT Sight, Glaukos, Iridex, Ivantis, New World Medical, Santen and Sight Sciences. Buznego reports he is a speaker and consultant for Glaukos and Allergan and a shareholder with Glaukos. Moster reports she was a primary investigator in the initial PreserFlo microshunt study. Radcliffe reports he is a consultant and speaker with Allergan, Alcon, Glaukos, Ivantis, New World Medical and Sight Sciences. Singh reports relevant financial disclosures with Allergan, Glaukos, Ivantis, New World Medical, Ellex, Sight Sciences and iStar Medical.
September 03, 2020
13 min read

When to use which MIGS approach is a nuanced decision

Source: Healio Interviews
Disclosures: Ahmed reports he is a consultant for Aerie Pharmaceuticals, Alcon, Allergan, Ellex, ELT Sight, Glaukos, Iridex, Ivantis, New World Medical, Santen and Sight Sciences. Buznego reports he is a speaker and consultant for Glaukos and Allergan and a shareholder with Glaukos. Moster reports she was a primary investigator in the initial PreserFlo microshunt study. Radcliffe reports he is a consultant and speaker with Allergan, Alcon, Glaukos, Ivantis, New World Medical and Sight Sciences. Singh reports relevant financial disclosures with Allergan, Glaukos, Ivantis, New World Medical, Ellex, Sight Sciences and iStar Medical.
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New devices, advancements in technology and unique MIGS approaches provide an expansive landscape for surgeons to manage IOP without invasive incisional surgeries or increasing medication burdens.

Since the approval of the iStent (Glaukos) in 2012, new devices and improved surgical techniques have continually advanced glaucoma treatment in the MIGS field. The ability to control glaucoma without intrusive surgery or additional medication has been a boon, according to Carlos Buznego, MD, an OSN Technology Board Member.

Carlos Buznego, MD
The MIGS approach to managing glaucoma is a better delivery of care, offering minimally invasive procedures that result in minimal complications, according to Carlos Buznego, MD.

Source: Carlos Buznego, MD

“Finding surgical procedures and techniques that have low complication rates and applying those techniques rather than always depending on more medication is key to better 24/7 pressure control. This is a space that not only offers minimally invasive procedures, but also results in minimal complications. That’s important,” Buznego said.

The MIGS approach has been a beneficial addition to the surgical armamentarium to help manage glaucoma. If glaucoma can be controlled with a MIGS device, it means less medication and expense for a patient, fewer phone calls with a pharmacy and reduced hassle for technicians and doctors. Better delivery of care solves multiple problems at the same time, Buznego said.

Long-term data needed

The premise of MIGS is to enhance quality of life, reduce medication dependence and control IOP while minimizing the need for topical drops. The benefit may not be clear until years later, when disease progression can be assessed, OSN Glaucoma Board Member Ike K. Ahmed, MD, FRCSC, said.

“That’s a hard thing to measure, and that was one of the outcome measures for the HORIZON study,” Ahmed said.

Ike K. Ahmed, MD, FRCSC
Ike K. Ahmed

The HORIZON study compared IOP lowering in patients with mild to moderate primary open-angle glaucoma undergoing phacoemulsification alone or combined with the Ivantis Hydrus microstent. The study showed the potential of MIGS and what it can do in terms of delaying or deferring glaucoma surgery, he said.

“Now that we see data 3 to 4 years later, we see a significant difference between both groups, the patients who went on to need further trabeculectomy surgery compared with those who did not,” Ahmed said.

Glaucoma is a progressive disease. Patients experience differing rates of progression, so long-term data for the MIGS space are needed, Inder Paul Singh, MD, Healio/OSN Board Member, said.

Placed in Schlemm’s canal, the Hydrus creates a bypass through the trabecular meshwork, allowing outflow of aqueous humor. In the HORIZON study, 556 patients with mild to moderate glaucoma were randomly assigned 2:1 to receive cataract surgery plus the Hydrus or cataract surgery alone. At 4 years, 65% of the patients who received the Hydrus remained glaucoma medication-free and 2.1% required subsequent invasive glaucoma surgery compared with 41% and 6%, respectively, in those who received cataract surgery only.

“What’s nice about data from the HORIZON study is that it shows not only the efficacy but also its long-term safety. When comparing the Hydrus with cataract surgery and cataract surgery alone, we find that patients with the Hydrus had a similar safety profile compared with cataract surgery alone and stabilization of endothelial cell density loss from 2 to 3 years and 3 to 4 years. Equally important, at 3 years, the Hydrus group had less chance ending up needing an incisional glaucoma surgery,” Singh said.

Severe glaucoma

Marlene R. Moster, MD, professor of ophthalmology at Thomas Jefferson University School of Medicine and attending glaucoma surgeon at Wills Eye Hospital, said that she tends to perform canal-based procedures first in patients with mild to moderate glaucoma because they leave the superior conjunctiva intact. However, in patients with severe glaucoma, a 20% reduction in IOP may not be enough.

For patients with severe glaucoma, a trabeculectomy to lower pressure by 40% to 50% should be considered. If the glaucoma can be first treated with MIGS, postponing trabeculectomy, that may possibly be all the surgery a patient needs in their lifetime, she said.

Marlene R. Moster, MD
Marlene R. Moster

“It is understood that the failure rate of trabeculectomy after 5 years is almost 50%. Therefore, a combination of a MIGS procedure initially and if needed a more aggressive approach like trabeculectomy or a tube later on makes the most sense. The longer we can keep the pressure in an acceptable range to halt visual field and optic nerve deterioration, the better it is for the visual health of the patient,” Moster said.

CyPass withdrawal

Demonstrated long-term safety is necessary in the MIGS space, and more long-term studies for devices are needed. The CyPass micro-stent was voluntarily recalled from the market in 2018 by Alcon after data from the COMPASS-XT study showed a statistically significant difference in endothelial cell loss at 5 years in patients who received the device with cataract surgery compared with those who underwent cataract surgery alone.

“We’re not seeing that divergence with the Hydrus. Whether it’s because of the material or because it’s more parallel with the trabecular meshwork as opposed to coming out more perpendicular, it’s hard to say. The point is that the safety data for the Hydrus is very promising, and we’re not seeing the same type of progression or divergence in the loss of cells,” Singh said.

The CyPass was a useful device in the supraciliary space, but its removal from the market left a gap for surgeons. It filled a number of needs, especially in patients who previously underwent trabecular meshwork procedures, according to Nathan M. Radcliffe, MD, Healio/OSN Board Member.

Nathan M. Radcliffe, MD
Nathan M. Radcliffe

The Xen gel stent (Allergan) has been particularly useful in filling the gap left by the CyPass, he said, and has been an appropriate replacement in patients with moderate to severe glaucoma in an off-label use.

Devices such as the MINIject (iStar Medical), designed to reduce IOP by enhancing aqueous humor outflow from the anterior chamber to the suprachoroidal space, is an investigational device that could be useful in the space if approved in the United States, Singh said.

PreserFlo may fill a need

Santen’s DE-128 microshunt, also known as PreserFlo, may also help fill the gap from the CyPass withdrawal, Buznego said.

Santen has partnered with Glaukos to bring the product to the United States. When implanted intraoperatively with 0.2 mg/mL concentration of mitomycin C, the microshunt reduces IOP in patients with primary open-angle glaucoma. The FDA accepted the premarket approval application for review of the microshunt in July.

In a multicenter study, the ab externo MIGS device reduced mean diurnal IOP from 21.1 mm Hg to 14.2 mm Hg at month 12 compared with a reduction from 21.1 mm Hg to 11.2 mm Hg in a standard of care trabeculectomy group.

“[PreserFlo] could theoretically be out at the end of the year. That’s a procedure where we’re diverting fluid from the anterior chamber into the subconjunctival space. Rather than a traditional MIGS procedure where we’re altering the traditional outflow, we’re looking at patients with damaged outflow, presumably with more advanced glaucoma, and we’re going to divert fluid out of the anterior chamber,” Buznego said.

It is similar to trabeculectomy and tube shunt surgeries, but it is less traumatic and more efficient, resulting in fewer complications and adverse events, he said.

The device is made from poly(styrene-block-isobutylene-block-styrene) or SIBS, a biocompatible, bioinert material that resists biodegradation.

“The appeal of this device is that it is standardized, requires minimal dissection by way of a fornix-based flap, does not require an iridectomy or a device cover, and may have fewer complications than trabeculectomy,” Moster said.

New MIGS strategies

While a number of companies are developing MIGS devices for the suprachoroidal space, newly devised strategies are available now for surgeons.

In Singh’s experience, most patients treated with the CyPass were on multiple medications with more moderate glaucoma. For these patients, Singh considers using a combination of MIGS.

Because it is unknown where the resistance to outflow is prior to surgery, viscodilation of Schlemm’s canal, whether with an Omni surgical system (Sight Sciences) or an iTrack microcatheter (Ellex), can help “hedge our bets” by flushing out the system and maximize outflow by breaking herniations in the canal and flushing out the distal collector channels. An effective strategy includes combining viscodilation and bypassing the trabecular meshwork with an iStent or Hydrus when performing cataract surgery, he said.

“What I’m seeing in my own hands is slightly better medication burden reduction than I see with stents alone or stents and viscodilation alone. That combination has helped me achieve a real reduction in medication burden,” he said.

Additionally, depending on whether the patient needs cataract surgery in conjunction with a MIGS procedure, Singh said a stent can be combined with viscodilation and added, if needed.

Inder Paul Singh, MD
Inder Paul Singh

Patients undergoing cataract surgery on multiple medications with a high IOP are good candidates for a combined stent, viscodilation and trabeculotomy or goniotomy. A 90° or 180° trabeculectomy/goniotomy can be performed away from the stent if more IOP reduction is required or if the glaucoma is moderate or severe, Singh said.

“That’s really how I’ve managed not having a CyPass in my hands recently,” he said.

Combining MIGS

Radcliffe said MIGS combination has been a useful strategy to address patients who are on two or more pressure-controlling medications.

For patients who are on multiple drops but suboptimally controlled, offering more than one MIGS makes sense.

“For the first iStent I implanted back in 2012, I actually combined it with [endocyclophotocoagulation]. The patient was on two or three drops, and I really felt like I knew what the iStent would give them. I wanted that, but I also thought I could get more out of it with an ECP,” Radcliffe said.

Conceptually, it is an effective strategy to do a variety of trabecular procedures with ECP for improved outcomes. Additionally, combining canaloplasty with a stent can be efficacious, he said.

Canaloplasty can be used to dilate the canal and expand the collector channels and outflow, Radcliffe said.

“Then, a surgeon can come in with the stents, either an iStent or a Hydrus, and lock it in by providing consistent access between the anterior chamber and the canal,” Radcliffe said.

In a retrospective study that evaluated outcomes of combined micro-bypass stent implantation, cataract surgery and ECP compared with ECP alone, Ferguson and colleagues found mean IOP was reduced 7.14 mm Hg from baseline in the combined group vs. 4.48 mm Hg in the control group (P < .01). The mean number of medications in the study group was reduced to 0.62 at 1 year, a 63% reduction from baseline.

MIGS choice

The algorithm for choosing MIGS is nuanced. It is individualized to the patient, the surgeon’s abilities and their practice, Radcliffe said.

Choosing MIGS can come down to a surgeon’s experience and comfort in using a device. The Kahook Dual Blade (New World Medical) and the iStent are both reasonable devices for surgeons to first gain experience. An excisional goniotomy with Kahook Dual Blade reduces the risk of a surgeon not accomplishing their goal, Radcliffe said.

“When choosing which device to use when, I think you have to acknowledge that without any comparative data, it is fair to say that it’s ‘dealer’s choice,’” Radcliffe said.

For example, the COMPARE study evaluated use of one Hydrus vs. two iStents as an off-label stand-alone treatment of open-angle glaucoma, and both devices reduced IOP and medication burden. At 2 years, more eyes in the Hydrus cohort were completely off medications.

It is a “fascinating” study, Radcliffe said, that exemplifies the difficulty of making a choice.

“People will argue all day long about which MIGS is better, but I think you need to look at the patient, the practice, insurance, cataract status and the surgeon’s experience,” Radcliffe said.

Tweaking approaches

When a MIGS device is approved, its story is still only half told. Surgeons modify and tweak approaches with the device and constantly look for advantages to improve outcomes. Durysta (bimatoprost implant, Allergan), the first approved intracameral sustained-release therapy for lowering IOP in patients with open-angle glaucoma, is a good example, as most surgeons have yet to decide the best way to implement the technology and in what scenarios, Radcliffe said.

This will come with experience. Once a device is approved, surgeons take a step back and evaluate how the implantation technique can be perfected, he said.

Surgeons modified the approach for the Xen gel stent, which was originally approved as an ab interno approach. Surgeons began implanting the stent with an external approach, which allowed for the placement of the distal tip in the subconjunctival space free of Tenon’s capsule, Buznego said.

“When we were implanting the stent from ab interno, from the inside of the eye to the outside of the eye, the distal tip often became embedded in Tenon’s capsule, and that leads to plugging of the stent and subsequently pressure elevation and then bleb failure. There was a separate technical factor, which is the ab interno approach involved needing to use the nondominant hand for half of your patients,” he said.

The transconjunctival external approach allows a surgeon to use their dominant hand for all eyes, it does not involve an anterior chamber incision, and it does not require the use of viscoelastic or sutures, Buznego said.

Previous scarring issues with the approach have been managed, for the most part, with subconjunctival MMC. Surgeons have drifted to higher concentrations of MMC to prevent scarring and bleb failure and, in some cases, are doubling the MMC strength to 0.4 mg per mL, Buznego said.

The external approach uses a previously approved billing code, CPT code 66183, insertion of anterior segment aqueous draining device, without extraocular reservoir, external approach, he said.

“It’s a permanent code, so in my experience it has allowed us to feel confident that Medicare and managed care organizations will cover the procedure,” Buznego said.

Technology is evolving

A device currently in clinical trials that shows promise is the Beacon aqueous microshunt (MicroOptx), which completed enrollment in the initial phase of its FDA investigational device exemption clinical trial in July, Singh said.

The Beacon lowers and controls IOP by shunting aqueous humor to the tear film. The clinical trial involves patients with refractory glaucoma receiving the device as part of a stand-alone procedure. The interventional, single-arm, open-label multicenter trial aims to evaluate the device’s safety and performance, along with IOP reduction.

“It’s very efficient, and from a surgical technique, it’s even more straightforward than some other MIGS. It does work very well. The question is risk of endophthalmitis, and so far, it looks promising. It will be interesting over time to see the fibrosis or failure rates,” Singh said.

Also in trials is the MINIject supraciliary device. The soft, flexible, microporous stent is implanted in the supraciliary space, but a very small part of the device remains in the anterior chamber, Singh said. In the company-sponsored first-in-human STAR-I study, patients achieved an average IOP reduction of 32.6%, to a mean of 15.6 mm Hg, at 1 year postoperative. Also at 1 year, 75% of patients were able to discontinue using topical medication, and corneal endothelial cell loss was minimal (mean change from baseline, –2%).

The future is wide open for MIGS technologies, and one of the most appealing directions it could lead to is noninvasive diagnostic tools to better tailor MIGS and help surgeons understand where the resistance outflow is coming from. Several companies are working to find that holy grail of where the resistance originates, he said.

“At the end of the day, there’s no right or wrong. People ask, ‘What is the perfect MIGS?’ Glaucoma is so multifactorial, the phenotype is so diverse, which is why we need multiple MIGS procedures. It often comes down to the comfort of the surgeon, the anatomy of the patient, the target pressure of the patient. One may ask why I don’t just use one or two MIGS devices. I would tell them it’s not fair to generalize our procedures for every patient, rather we can now tailor the right procedure for the right patient. That’s why I use them all,” Singh said.

The future of the space involves evaluating which patients do best with which MIGS and which surgical approach, Ahmed said. This requires big data, analytics, better imaging, better understanding outflow mechanisms, synergy with drug delivery, and development of future IOP sensors and feedback mechanisms.

The opportunity to offer MIGS is here, and surgeons are getting a better feel for selecting patients and choosing the correct technique to optimize outcomes. Despite the advancements, there is still much to learn, Ahmed said.

“Being proactive is what counts and ensuring that we take a more interventional approach in the future. We’re seeing this in the SLT LiGHT study, by controlling pressure with reduction of topical or no topical medications. Even with IOPs being similar, we see fewer patients go on to need further or more major glaucoma surgery. It is a nice message that is certainly resonating,” he said.

Click here to read the Point/Counter to this Cover Story.