MIGS: Expanding Options for Glaucoma Treatment

Update: On Aug. 29, 2018—after the article below went to press—Alcon announced a voluntary, global recall of the CyPass microstent.

Download PDF

In the decade since Iqbal Ike K. Ahmed, MD, coined the term microinvasive glaucoma sur­gery—better known as MIGS—the field has grown exponentially.

Dr. Ahmed noted several reasons for the growing interest in MIGS: “Compliance is really poor in glaucoma patients, and even if the patient is compliant, quality of life and the high costs of medicine continue to be issues. We must continu­ally look for solutions for these patients. MIGS are moving in that direction,” said Dr. Ahmed, who is a glaucoma specialist with the Prism Eye Institute in Mississauga, Ontario, Canada.

An online survey of glaucoma surgery practice preferences conducted by the American Glaucoma Society found that among patients who had initial surgery for primary open-angle glaucoma (POAG), the percentages were 59% for trabeculectomy with mitomycin C (MMC), 23% for a glauco­ma drainage device (GDD), and 14% for MIGS. When the glaucoma procedure was combined with cataract surgery, the percentages were as follows: trabeculectomy with MMC, 24%; MIGS, 22%; and GDD, 9%.¹

The survey also found that iStent and Trabectome were the most commonly used MIGS proce­dures in 2016.

Debating the Role of MIGS

Although multiple studies have associated MIGS with a favorable safety profile and modest efficacy, others cite a lack of evidence in proving the effec­tiveness of these techniques.

In response to “good, healthy skepticism” from some quarters, Dr. Ahmed said that “MIGS have been very well studied for many years, with a wealth of published data.” He emphasized that MIGS are not designed to replace trabeculectomy in advanced glaucoma. Rather, “Surgeons are using MIGS procedures in their mild to moderate pa­tients who need lower intraocular pressure (IOP) but in whom they are reluctant to operate because of the side effects associated with trabeculectomy.”

The Case for MIGS

Glaucoma specialist John P. Berdahl, MD, with Vance Thompson Vision in Sioux Falls, South Dakota, said he considers the entire range of MIGS options when tailoring treatment for his glaucoma patients.

Fitting the procedure to the patient. “It is my duty to fit the procedure to the patient,” Dr. Berdahl noted. “That being said, when you are first starting out with MIGS, it is good to get comfortable with one procedure and then expand out to other pro­cedures because there are a lot of similarities.” He added that the learning curve for a MIGS proce­dure is between 10 and 20 cases.

Dr. Berdahl discussed his 3-year results from patients who had an iStent implanted in com­bination with cataract surgery.² “This approach effectively lowered IOP in open-angle glaucoma (OAG) patients from a mean of 19.13 ± 6.34 mm Hg to 15.17 ± 3.53 mm Hg after 2 years,” he said. “Interestingly, we found that the magnitude of IOP reduction was more significant in patients with higher preoperative pressure and also that medication use was significantly reduced.”

An “early adopter’s” experience with iStent. Glaucoma specialist Mark J. Gallardo, MD, of El Paso Eye Surgeons in Texas, is an “early adopter” of several MIGS procedures, an interest fueled by his desire to provide patients with the most advanced technology, especially if it proves safer, with a quicker recovery.

Dr. Gallardo believes that the modest results from the early clinical trials of the iStent do not reflect the full potential of this approach, as the trial investigators were the first in the world to use the device in a clinical setting and had minimal experience in the best placement. He noted that 70% of the stents were implanted by surgeons who had performed 5 or fewer procedures.

“The learning curve, as well as the previous lack of knowledge on how to maximally manip­ulate the outflow system with targeted stent im­plantation, adversely impacted the data,” he said.

Placement and patients. Ultimately, surgeons, including Dr. Gallardo, learned that targeting areas adjacent to collector channels could enhance the efficacy of the stent. Intraoperative visual cues, such as increased regurgitation of blood (blotch­ing) within Schlemm’s canal or increased areas of pigmentation on the posterior trabecular mesh­work, help to highlight the location of patent collector channels.

“This, coupled with our identification of ideal candidates for the procedure—those already on 1 to 3 glaucoma drugs with IOP targets in the mid-teens range—have led to results superior to those of the pivotal trial, and subsequent research has demonstrated the safety and effectiveness of the trabecular microbypass stent [iStent],” he said.

Case series shows benefits. Dr. Gallardo con­ducted a retrospective case series in a predomi­nantly Hispanic patient population with moderate to severe glaucoma to assess reduction of IOP and/ or medication burden at 12 months following implantation of 1 trabecular microbypass stent during cataract surgery.³

Results of the entire cohort showed that IOP was reduced from 16.5 mm Hg preoperatively to 12.9 mm Hg, and the mean number of medications decreased from 2.3 to 0.9.

Reducing medication burden. “At 12 months, 94% of all eyes achieved their predefined treat­ment goal of reduced IOP and/or medications,” Dr. Gallardo noted. Among patients who had medically controlled glaucoma entering cataract surgery plus stent implantation, 69% were able to completely eliminate their need for medications. Of this latter group, 55% had been on 3 or more medications preoperatively, he said.

“The earlier we use MIGS, the less we need to rely on medications,” Dr. Gallardo said.

He noted several benefits from reducing a pa­tient’s medication burden: increased compliance, lower monthly costs (generic drugs are skyrocket­ing in price), and less exposure to the preservative benzalkonium chloride, which has been associated with ocular surface disease and damage to endo­thelial cells in the trabecular columns.

KEY STEPS IN GATT. (1A) Initial cannulation of Schlemm’s canal. (1B) The microcatheter (or suture) has been passed 360 degrees around the canal. (1C) The distal tip of the catheter/suture has been retrieved and is being externalized, creating the circumferential trabeculotomy. KEY: 1, Schlemm’s canal (SC); 2, initial goniotomy site; 3, microsurgical forceps; 4, either the microcatheter or suture; 5, distal end of the catheter/suture after it has been passed around SC; 6, path of the catheter/ suture within SC; 7, trabecular shelf created by this procedure; 8, trabeculotomy resulting from GATT.

ABiC: Impact on Practice

Dr. Gallardo also performs ab interno canaloplasty (ABiC), or transluminal viscodilation, which aims to improve outflow by dilating Schlemm’s canal 360 degrees through a small corneal incision, using a microcatheter and viscoelastic.

Pearls for ABiC. He makes the temporal clear corneal wound directly across from the nasal angle with side-port incisions at a 90-degree angle. He recommends avoiding the limbal vessels as much as possible, as surface bleeding can stain the visco­elastic used as a coupling agent for the gonioscope and obstruct the view of the drainage angle.

Dr. Gallardo uses the iTrack catheter, which, he said, “provides tactile feedback on the patency or health of the canal during circumnavigation, while the illuminated tip allows me to track the catheter’s movement, providing me assurance that I am actually in the canal and not in the supracho­roidal space.”

What about moderate to severe glaucoma? Dr. Gallardo said that the advent of MIGS has had an enormous impact on his practice, not only in his treatment of patients with mild glaucoma but also in those with moderate to severe glaucoma.

“Whether [they are] performed as a standalone procedure or as an adjunct to cataract surgery, I have found these microinvasive procedures very effective at meeting my patients’ needs,” he said. “In patients requiring further reduction in IOP, I try a MIGS procedure or a combination of MIGS procedures before filtering, in most but not all circumstances.” He added, “I was doing 8 to 10 filters a week, and now I perform 1 ab externo filtration every 4 to 6 weeks.”

TRABECTOME + ABIC. (2A) Trabectome is used to remove a sector of trabecular meshwork. (2B) ABiC is performed through the Trabectome’s ablation zone.

GATT: A New Twist on Trabeculotomy

While ABiC is a minimally invasive approach to canaloplasty, gonioscopy-assisted transluminal trabeculotomy (GATT) is a minimally invasive modification of standard trabeculotomy.

“When I was a medical student, I felt that trabs and tubes seemed really harmful to the eye, and I kept questioning why we were doing what we were doing,” said glaucoma specialist Davinder S. Grover, MD, MPH, of the Glaucoma Associates of Texas in Dallas.

“I started practice right around the time the iStent was being investigated,” Dr. Grover added. “My partners and I were primary investigators on the CyPass microstent, Hydrus, and XEN gel stent. Additionally, Dr. Ronald L. Fellman and I were developing techniques of our own (ab interno bleb revision and ab interno Ex-PRESS shunt removal), and all this research converged to provide a pro­ductive environment for our own innovations.”

Development of GATT. Drs. Grover and Fellman (along with their colleagues Drs. David Godfrey and Oluwatosin Smith) developed the GATT procedure, an ab interno circumferential trabeculoto­my that is performed through 2 corneal incisions, 1 mm each. A small goniotomy is created, and a microcatheter or 5-0 Prolene suture is used to cannulate 360 degrees of Schlemm’s canal and then unroof the entire trabecular meshwork (Fig. 1).

Dr. Grover said a major advantage of this procedure is that the entire drainage system is accessed, rather than just a small portion. In ad­dition, it spares conjunctival tissues from incision and scarring, allowing better outcomes if tradi­tional glaucoma surgery is required later.

Findings from 2 studies. In the first study, “we looked back at our 2-year data on 10 patients (14 eyes) under 30 years old with a dysgenic anterior segment angle and uncontrolled primary congen­ital glaucoma or juvenile open-angle glaucoma who underwent GATT,” Dr. Grover said. “They experienced a mean decrease in IOP from 27.3 to 14.8 mm Hg and a mean decrease in meds from 2.6 to 0.86.⁴

“Moreover, when we evaluated GATT out­comes in 198 patients with POAG and secondary open-angle glaucoma (SOAG), either isolated or combined with cataract surgery, we found very encouraging results that were similar to if not bet­ter than previously published data on ab externo circumferential trabeculotomy,” Dr. Grover said.

The patients in this study with POAG had an average IOP decrease of 9.2 mm Hg (a mean re­duction of 37.3%) at 24 months, with an average decrease of 1.43 glaucoma medications.

At that same time point, the SOAG patients had an average decrease in IOP of 14.1 mm Hg (a mean reduction of 49.8%) on an average of 2.0 fewer medications.⁵

Learning from failure. While Dr. Grover was pleased with the results, he gained greater insight from the treatment failures. In the POAG group, there was a correlation between mean devia­tion (MD) in visual field defect parameters and outcomes: Patients with a worse MD had a higher chance of treatment failure in the first 3 months.

“This is suggestive of the health of the eye’s inherent drainage system,” Dr. Grover said. “Since it is difficult to visualize the collector channels and episcleral vasculature, we searched for other in­dicators that would serve as a proxy to determine the patency of the outflow system.”

The wave as an indicator. In seeking such a proxy, Drs. Fellman and Grover drew on their experience with an earlier MIGS, Trabectome. During that type of surgery, they had observed a nasal perilimbal and/or episcleral vessel wave of fluid adjacent to the trabeculotomy site. “We be­lieve this fluid wave, which we named an episcleral venous fluid wave (EVFW), signifies intraopera­tive structural patency of the conventional outflow system and is a sign that the collector system is at least anatomically functional.”⁶

Dr. Grover said the presence or absence of this EVFW could be a prognostic indicator for success after a Trabectome surgery. In a study of 68 eyes of 49 patients with glaucoma who underwent phaco plus Trabectome or Trabectome alone, the eyes with a poorly defined EVFW had a higher likeli­hood of further glaucoma surgery.⁷

He uses the EVFW as a prognostic sign for GATT as well. “When I perform a GATT and I see an EVFW, I am very optimistic about that surgery.”

TSCPC + ABIC. (3A) After micropulse TSCPC is completed, (3B) ABiC is performed.

Combined MIGS Procedures

One of the hot topics at the American Glaucoma Society’s 2017 annual meeting was combining MIGS procedures. Won I. Kim, MD, a glaucoma specialist with Walter Reed National Military Medical Center in Bethesda, Maryland,* gave a presentation suggesting that multiple MIGS procedures can be successfully combined without significant additional risk.

Dr. Kim said, “Because of their relatively modest efficacy, MIGS procedures have traditionally been limited to mild to moderate disease; but perhaps combined MIGS proce­dures, with their potentially improved efficacy, can be extended to include those with severe disease.”

Mix-and-match MIGS. Dr. Kim has been mixing and matching MIGS proce­dures, based on specific patients’ needs. One of these combinations is ab interno trabeculectomy plus ABiC.

“My approach was removing a section of trabecular meshwork with the Tra­bectome or Kahook Dual Blade and then visco­dilating the rest of Schlemm’s canal 360 degrees with the iTrack,” Dr. Kim said (Fig. 2). “This could take advantage of the different mechanisms of both sectoral trabecular meshwork removal and canaloplasty while simultaneously addressing their weaknesses,” such as the limited sectoral aspect of Trabectome and the residual trabecular meshwork resistance after canaloplasty.

He has also successfully used several other multi-technique approaches. These include ABiC com­bined with micropulse transscleral cyclophotocoagulation (TSCPC; Fig. 3), trabecular meshwork bypass (using either iStent, GATT, or Trabectome) combined with endoscopic cyclophotocoagulation (ECP; Fig. 4), and CyPass supraciliary stent com­bined with trabecular meshwork bypass (using iStent or Kahook Dual Blade; Fig. 5).

He said that in his experience, all of these tech­niques have shown the ability to lower IOP into the low-teens range, reduce medication burden, maintain an excellent safety profile, and allow for rapid visual recovery.

Multi-MIGS plus phaco. Dr. Berdahl is also an advocate of combined MIGS. He compared the outcomes of combined microbypass stent implantation, cataract extraction, and ECP to those obtained with just the microbypass stent and concomitant cataract surgery in patients with OAG.⁸

He found that patients who underwent the combined approach experienced a mean IOP reduction of 7.14 mm Hg compared with 4.48 mm Hg in the control patients who did not have ECP. He found that the combination procedure was also effective in patients with severe OAG.

“The combined approach makes sense,” Dr. Berdahl said. “We are trying to avoid the morbidity of more aggres­sive glaucoma surgeries. The question then becomes whether the efficacy is good enough. My approach is safety first and efficacy second. I will try the MIGS first.”

GATT + ECP. (4) TRAB 360 handpiece is used to perform GATT, which is followed by ECP.

MIGS Caveats

Steven L. Mansberger, MD, MPH, of the Devers Eye Institute in Portland, Oregon, has closely watched the advent of MIGS. He expressed con­cerns in the areas of efficacy and costs.

“As a glaucoma specialist, I am always interested in finding new ways of lowering pressures safely and effectively, and I applaud the investigators in this space,” Dr. Mansberger noted.

“That being said,” he added, “MIGS may be use­ful for some patients, but traditional surgeries are required by the vast majority of surgical glaucoma patients, and it is imperative that we continue to learn the ins and outs of trabs and tubes in our glaucoma fellowships.”

Efficacy concerns. Dr. Mansberger pointed out that some MIGS such as the iStent make only a millimeter of difference in IOP, and “we do not understand the characteristics of patients who most benefit from MIGS above and beyond cata­ract surgery alone.”

Dr. Mansberger recounted a number of earlier implant devices that had failed, including several limbal and suprachoroidal stents in the 1950s and 1960s, and a XEN-like implant in the 1980s.⁹

“We have new modifications such as mitomycin C [e.g., with XEN implants],” he added. “But time will tell if these new MIGS will be more effective or if history will repeat itself.”

Cost factors. The downside of many of the MIGS surgeries is their cost, Dr. Mansberger pointed out. MIGS such as iStent, XEN, and Trabectome can add up to $4,000 to the cost of cataract surgery alone when factoring in surgeon charges, device costs, anesthesia costs, and surgical center fees. “We need to look at changing the cost-benefit ratio in terms of costs,” Dr. Mansberger said.

On the other hand, he noted that the GATT procedure is one of the most cost-effective MIGS—it can be done using a $5 suture. “And Dr. Grover has shown good results 2 to 3 years out, making this the approach to watch,” Dr. Mansberger said.

Multiple surgeries? He also has concerns about patients who may need subsequent surgeries if a MIGS procedure does not effectively lower IOP.

“In most patients we see who can’t use their drops or who have severe glaucoma, we do a traditional procedure, and we only need to operate one time to treat the problem. That is preferable to multiple surgeries,” he said.

“Down the road, MIGS will be considered based on cost, IOP response, and visual field outcomes,” said Dr. Mansberger. “Through the efforts of these MIGS pioneers, we will learn more about how to better treat glaucoma. We don’t have the perfect MIGS yet, but in the end, we will get there.”

CYPASS + ISTENT. (5A) CyPass is placed in the supraciliary space. (5B) iStent-L is placed, followed by an iStent-R facing in the opposite direction (not shown). The 2 iStents and a CyPass allow aqueous outflow through multiple pathways.

The Next Phase: Sustainability

Dr. Ahmed expressed a similar view regarding future developments. He said that while it has been greatly satisfying to be involved in the early innovation process and see a large number of MIGS procedures “go mainstream,” he had not fully anticipated the need for research on their cost-effectiveness and appropriate utilization.

Reimbursement challenges. “We are currently recognizing and building the right studies to look at quality-of-life issues, helping payers in the United States and Canada understand why MIGS should be funded a certain amount,” Dr. Ahmed said. “We are looking at recovery, number of postsurgical visits, return to vision, and refractive changes—metrics that are of concern to entities funding these procedures.”

Dr. Berdahl also pointed to reimbursement as one of the biggest chal­lenges to widespread MIGS adoption. “MIGS is one of the only really impres­sive innovations in glaucoma in the last few decades. It will be tremendously sad if it withers on the vine,” he said, for lack of reimbursement and resources to support innovation.

___________________________

*The views expressed are those of the individual and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. government. Any mention of products is for informational purposes only and should not be considered an endorsement.

___________________________

Be sure to check out “MIGS Reimbursement,” a Web Extra for February’s Feature.

___________________________

1 Vinod K et al. J Glaucoma. 2017;26(8):687-693.

2 Ferguson TJ et al. Clin Ophthalmol. 2016;10:1767-1773.

3 Gallardo MJ et al. Clin Ophthalmol. 2016;10:1931-1937.

4 Grover DS et al. Br J Ophthalmol. 2015;99(8):1092-1096.

5 Grover DS et al. Gonioscopy-assisted transluminal trabecu­lotomy: an ab interno circumferential trabeculotomy midterm follow-up. Paper presented at: annual meeting of the American Academy of Ophthalmology; Nov. 17, 2015; Las Vegas.

6 Fellman RL, Grover DS. J Glaucoma. 2014;23(6):347-350.

7 Fellman RL et al. Opthalmology. 2015;122(12):2385-2391.

8 Ferguson TJ et al. J Cataract Refract Surg. 2017;43(3):377-382.

9 Lim KS et al. Br J Ophthalmol. 1998;82(9):1083-1089.

Web Extras