Surgeons seek criteria for selecting new MIGS options

After years of being at a standstill, glaucoma treatment has entered a new era of microinvasive surgery. A wide choice of techniques and technologies is now offered to patients who historically would have been cuffed to a lifelong sentence of drops. Such a proliferation of options, however, carries the risk of creating information overload and confusion.

“I hate to say it, but I think the amount of options and choices can confuse many doctors. ‘What do I do now?’ I hear all the time from my colleagues. People are wondering which procedure or device to implant in a specific patient and seek guidance on what is best to do in a certain situation and why,” Inder Paul Singh, MD, said.

The scenario appears to be similar to that of premium IOLs. As new designs proliferated, including bifocal, trifocal, increased depth of focus and many other options, the issues of what to do, when and why were raised, leading to lively debate.

“This is the kind of discussion we should have with MIGS devices now. Indications, criteria and what lays behind failure or success will be key subjects for future investigation,” Singh said.

Image: Singh IP

Best candidates for MIGS

MIGS in general is best indicated for patients with mild to moderate glaucoma, typically on one or two medications, Robert J. Noecker, MD, said.

“Those who have a very high risk of getting worse and have poorly controlled IOP are probably not the best candidates,” he said.

An important subgroup of patients is those with glaucoma and cataract because combination with cataract surgery is required for the on-label use of several MIGS technologies. The two surgeries are easy to perform together and act synergistically toward decreasing IOP.

“It is worth taking the opportunity to have this small incremental benefit because the way I think about using MIGS is not a cure for everything but taking steps in the right direction. Maybe we can drop one medication and decrease the eye pressure by five points. For some patients, this is all that’s needed and a wonderful thing. The milder spectrum of patients and those who need cataract surgery are most of our patients anyway,” Noecker said.

Anatomy is also a key factor, meaning open-angle glaucoma, primary or secondary, Nathan Radcliffe, MD, said. In addition, patients should have realistic expectations.

“This is important because we know that MIGS can lower pressure well, but from the mid or low 20s to the mid or even high teens in some cases. You want to make sure that the eye is going to do well with that type of pressure reduction,” he said.

Balancing safety and efficacy

Currently, there are no established, evidence-based criteria to help navigate through the many MIGS options and select the appropriate solution for individual patients.

“Until we have head-to-head comparative data, we must rely on anecdote and intuition. For me, surgery involving the canal is safest, followed by supraciliary and then transscleral options. Meanwhile, while the transscleral MIGS procedures may have more risk, they likely afford the greatest efficacy,” OSN Glaucoma Section Editor Thomas W. Samuelson, MD, said.

Because glaucoma is a heterogeneous process, the response to treatment is also variable; some patients may respond well to canal procedures while others may require a complete bypass of the conventional system.

“Fortunately, we now have supraciliary and transscleral options with the recent approval of CyPass (Alcon) and Xen (Allergan). And of course, we should not forget that our traditional surgeries such as trabeculectomy and tubes work very well for our more severe and/or rapidly progressing patients,” he said.

Among the most important considerations is a risk assessment of the disease process itself, Samuelson said, “making certain that the risk of the procedure that is recommended does not exceed the risk of the disease.”

According to Singh, multiple factors have to be considered. Efficacy should be balanced with ease of implantation, safety and postoperative management. For instance, the iStent trabecular micro-bypass stent (Glaukos) and canal dilation procedures such as Kahook Dual Blade (KDB, New World Medical), Trabectome (NeoMedix) and ab interno canaloplasty (iTrack by Ellex and Visco 360 by Sight Sciences) have the highest safety profile because there is no hypotony or bleb formation.

“However, there is a limit to how low we can go with our target IOP since we are dealing with the episcleral venous pressure of the natural outflow system,” he said.

If IOP in the low teens is needed, Xen is probably better but carries a slightly higher adverse event profile and requires some more postoperative management to deal with the bleb.

“Also, these various procedures require a slightly different skill set and amount of time in the OR,” Singh said.

Anatomy, patients’ risk attitude, cost

Assessment of the conjunctiva and angle anatomy is mandatory in guiding the choice for devices, according to John P. Berdahl, MD.

“Clearly if there is a lot of subconjunctival scarring, a device that goes subconjunctivally would be a challenge. However, trying to differentiate between a trabecular bypass or a suprachoroidal stent or a supraciliary stent is more difficult. There are some clues you can assess gonioscopically, like if there is access to the trabecular meshwork. If there is no access, ie, if the angle is closed, then a trabecular stent is likely out, but you could perhaps still use a suprachoroidal stent,” he said.

Patients’ needs and expectations and how different types of MIGS can satisfy them are Radcliffe’s first priorities. In his opinion, the balance between safety and efficacy and the patient’s risk attitude should be thoroughly discussed to reach a joint decision.

“I see the trabecular micro-bypass as a strategy to lower the pressure modestly but being exceptionally safe with basically no risk of hyphema. I would offer that type of procedure to patients who themselves are risk-averse and have very mild disease,” he said. “With another patient who is very concerned about going blind, who has a family member who went blind, is on two drops and has moderate disease, I am going to choose something that opens up the canal much more. The drawback is often a risk of hyphema and some other complications. So, again, I am looking at the patients, their own narrative, their own understanding of the disease and willingness to take the risk to control the glaucoma better, and choose different devices based on the patient’s profile.”

Other deciding factors are reimbursement and approved indications. The iStent and CyPass are only indicated at the time of cataract surgery, and so even if a surgeon wants to “save” the trabecular meshwork and maybe do a CyPass later on if needed, the second procedure will not be covered as a standalone.

“There are many phakic and pseudophakic patients who are able to have ab interno canaloplasty, KDB or the Xen stent, but not a CyPass or iStent. This may change as the new-generation iStent is hopefully going to be approved as a standalone,” Singh said.

Evaluating outflow resistance

MIGS approaches have gathered new interest around the structure and functioning of the aqueous outflow system. Trabeculectomy and tubes completely bypassed the natural pathways by creating a drainage hole in the eye, so there was no need to know where the resistance to outflow was in patients undergoing surgery. Now, because each of the MIGS devices works in a different part of the outflow system, the efficacy and responder rates are likely to depend on where the resistance is, Singh said.

“For instance, if the resistance is primarily in the trabecular meshwork (TM), then an iStent or other TM bypass devices should have good efficacy. If the resistance is primarily in the Schlemm’s canal, maybe a canal-dilating procedure such as iTrack ab interno canaloplasty, Visco 360 or Kahook Dual Blade might be needed. If it is both, maybe a device that works on both the TM and canal might be beneficial, like the KDB, canaloplasty or Hydrus microstent (Ivantis), coming out in the future, although an iStent still may help in these cases as well. If it is distal to the canal, then maybe a suprachoroidal device such as the CyPass or a subconjunctival device like the Xen might work,” he said. “These are just conceptual approaches to the various procedures. It is important to note that there is a crossover of effect on the outflow system. Therefore, a device working primarily on the TM still may have an effect on the canal. There are no steadfast rules to this.”

Today the ability to localize the site of maximal resistance is primitive, but considerable research is targeted toward identifying and mapping the outflow system, Samuelson said.

“Such testing would be extremely valuable in helping to determine which procedure is most useful for a given individual. Currently, decisions are made based on optic nerve damage rather than site obstruction. One day we will tailor our surgical intervention toward the site of the specific outflow pathology,” he said.

Technology in evolution

Currently, no tool is available clinically to precisely locate along the aqueous pathway the primary source of outflow resistance. Attempts to map out the aqueous outflow structure and/or function have been made by using tracer dyes and advanced ophthalmic imaging. Recent modalities include canalography, aqueous angiography, episcleral venous fluid wave and high-resolution spectral-domain OCT. They all are contributing to unveil the complex dynamics of the system but have limitations and are still far from offering clinically relevant advantages.

“In an ideal world we’d understand the site of outflow resistance, so if we knew that the trabecular meshwork was the site of resistance, it would be ideal to bypass that; if we knew that episcleral venous pressure was high, it would be ideal to bypass the episcleral venous pressure and use a suprachoroidal or a subconjunctival stent. That would definitely be the best way to differentiate among the MIGS devices,” Berdahl said.

He regards methods to measure episcleral venous pressure as particularly promising, with far-reaching implications for treatment selection on both the surgical and pharmacological sides.

“For instance, Rho kinase inhibitors may lower episcleral venous pressure, and so if we are able to determine that episcleral venous pressure is high, then we may be able to determine which pharmacotherapy or which MIGS therapy or which combination of the two will be most effective,” he said.

A technology able to evaluate the aqueous pathway is a theoretical goal that everyone would like to see in order to be able to characterize each patient’s outflow system, according to Noecker.

“We are not too far from this goal. OCT and other imaging technologies are getting close to evaluating if the Schlemm’s canal is collapsed or the collector channels in the area are functional or not. But we don’t have this technology readily available in our clinical practices right now,” he said.

“In some cases we know that there is obstruction in the TM from trauma or pigmentary glaucoma. Then we look for alternative ways to lower IOP, maybe implanting a supraciliary or suprachoroidal shunt, or working on the aqueous decrease. However, besides these cases, we don’t have the technology to evaluate how good the TM is and whether it is worthwhile doing a trabecular meshwork-based surgery,” Noecker said.

SLT as a diagnostic tool

Singh supports the use of selective laser trabeculoplasty not only as a treatment for glaucoma but also as a diagnostic tool. SLT works by releasing macrophages and cytokines to “open up” the trabecular meshwork. Therefore, if the primary source of resistance is in the trabeculum, SLT results are good. Conversely, if blockage is primarily in the canal or distal channels, SLT may not be as effective.

“With this in mind, I do think we can use SLT as a preoperative assessment of where the resistance might be,” Singh said.

He analyzed his iStent retrospective data and found good results overall, with 70% of patients achieving IOP of 16 mm Hg or less with 0.8 medications. Looking at the subset of patients who had SLT before iStent implantation, it was evident that those who responded well to SLT also had a good response to the iStent. Vice versa, those who did not respond well to SLT did not respond well to iStent either.

“This makes sense since SLT is working primarily at the level of the TM. So now, we may want to think about offering SLT as a first-line treatment, not only to help our patients get off medications, reducing cost and side effects, but also to help us understand where the resistance is for future MIGS surgical selection,” Singh said.

Combining MIGS for increased efficacy

Given that MIGS technologies are not mutually exclusive, combinations based on anatomy and target pressure are a possibility.

“What we do offer more and more is mix and match with devices and other modalities that work at a different level. Options include TM-based devices, suprachoroidal space devices and those that decrease aqueous production. I have mixed trabecular micro-bypass with endoscopic cyclophotocoagulation and at the same time a suprachoroidal shunt. Here you find the maximum combination. They all work differently and have a good chance to lower the pressure more than any of these procedures alone,” Noecker said. “I am not sure which procedure is doing the most in individual patients. We are hedging our bets a little bit.”

Attacking the problem in different ways is a strategy that parallels what is done with medical therapy when different classes of medications are used together to increase the chances of success — in this case, falling within the target pressure range.

“If the patient doesn’t want trabeculectomy but we need to lower the pressure more than a single MIGS procedure could do, we can mix and match. The nice thing is that the risk does not go up very much when we combine these options together,” Noecker said.

The choice largely depends on the patient’s willingness to have multiple procedures, Radcliffe said.

“If a patient voices to me that he or she is happy to go back to the operating room as many times as it takes, has good vision and wants to preserve it, I’m going to start with something very minimally invasive like the iStent. Then I might move on to larger areas of trabecular micro-bypass and then maybe to suprachoroidal or subconjunctival approaches,” he said.

Cost and reimbursement issues also come into play, including the patient paying out of pocket.

“A lot of these MIGS are using T codes. Some of those are approved by Medicare, others are not, some are not reimbursed by any insurance, others by half the insurances, and it tends to be the more traditional procedures such as goniotomy and viscocanalostomy that are approved by all the insurances and not coupled with cataract surgery,” Radcliffe said.

Experience leads to better practice

“The biggest nice thing is that all of a sudden we have the problem of so many options. We have relative short-term experience and are still learning on what works best in which patient and what is the optimal surgical technique. I changed the way I implant the devices in the last couple of years,” Noecker said.

Experiences are diverse and personal at this stage, and advice on which device to use in which case would be based purely on personal opinions, Radcliffe said.

“My algorithm is not going to be the same as other doctors. They may have a different technique, and they may have different outcomes and a different safety profile with each different procedure. So, my advice to colleagues is to learn every procedure and take a look at how their patients do, what efficacy they get and what kind of side effects they see, and to tailor each device to the patients, to their personality, to their personal narrative,” he said.

In Radcliffe’s two practices, one in the Bronx and one in Manhattan, the performance of some of the MIGS devices is strikingly different.

“It could be because one practice has seen earlier disease; it could be because one practice has a different makeup of demographic factors or compliance issues. It’s complex, but when I go to practice A I use a certain MIGS strategy and when I go to practice B I use something else,” he said. “That’s the kind of tailored therapy we are looking at. We need to gain experience with all the devices and offer the best to each patient, based on the best available data and our own clinical and surgical experience.” – by Michela Cimberle

• References:
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• For more information:
• John P. Berdahl, MD, can be reached at Vance Thompson Vision, 3101 W. 57th St., Sioux Falls, SD 57108; email: john.berdahl@vancethompsonvision.com.
• Robert J. Noecker, MD, MBA, can be reached at Ophthalmic Consultants of Connecticut, 1375 Kings Highway, Fairfield, CT 06824; email: noeckerrj@gmail.com.
• Nathan Radcliffe, MD, can be reached at NYU Ophthalmology Associates, 240 East 38th St., 13th Floor, New York, NY 10016; email: drradcliffe@gmail.com.
• Thomas W. Samuelson, MD, can be reached at Minnesota Eye Consultants, 710 E. 24th St., Suite 100, Minneapolis, MN 55404; email: twsamuelson@mneye.com.
• Inder Paul Singh, MD, can be reached at The Eye Centers of Racine and Kenosha, 3805B Spring St., Suite 140, Racine, WI 53405; email: inderspeak@gmail.com.

Disclosures: Berdahl reports he is a consultant for Calhoun, ClarVista, DigiSight, Envisia, Equinox, Glaukos, Imprimis, Ocular Therapeutix, Omega Ophthalmic, Ocular Surgical Data, Vision 5 and Vittamed. Noecker reports he is a consultant for Alcon, Allergan, BVI, Iridex and Santen. Radcliffe reports he is a consultant for Alcon, Allergan, Glaukos, Iridex, Lumenis, New World Medical and Transcend Medical. Samuelson reports he is a consultant for Alcon, Allergan, Abbott Medical Optics, AqueSys, Endo Optiks, Glaukos, iScience, Ivantis, Pfizer, QLT and Santen. Singh reports he is a consultant for Allergan, Glaukos, Bausch + Lomb, Ellex, Aerie Pharmaceuticals, Imprimis, Shire, NovaBay and Katena.

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