The traditional approach to glaucoma treatment has changed little over the past 50 years. To lower intraocular pressure (IOP), glaucoma physicians generally begin by prescribing topical medications, followed by trabeculoplasty and, if necessary, filtering surgery. A shift in the treatment paradigm occurred two decades ago with the development of minimally invasive (or microinvasive) glaucoma surgeries (MIGS). These MIGS procedures and devices have proven to be highly beneficial, as they provide an opportunity for surgical management of mild to moderate early glaucoma without the risks associated with traditional procedures like trabeculectomy or implantation of glaucoma drainage devices (GDDs).

MIGS devices work by addressing many different pathways of action. Some MIGS aim to lower IOP by creating or enlarging aqueous outflow routes within the eye. Trabecular meshwork (TM) is generally considered to have the greatest resistance to aqueous outflow; TM can be bypassed with stents or tissue can be removed via goniotomy or trabeculotomy to increase outflow into Schlemm's canal. Another approach involves dilation and expansion of Schlemm's canal and collector channels with a viscoelastic device. There are several devices that enable surgeons to easily combine viscodilation and TM bypass or excision. In cases where these approaches are unlikely to work, aqueous can also be shunted into the subconjunctival space through an ab interno, small incision approach (Table 1).

Endocyclophotocoagulation (ECP), another minimally invasive approach, involves ablating ciliary processes to reduce aqueous production. In this approach, an endoscopic diode laser probe is inserted through a clear corneal incision to treat the ciliary body, in order to reduce production of aqueous.

MIGS procedures are usually performed at the same time that the patient is undergoing cataract surgery. Most stents, for example, are only approved for placement during cataract surgery, and payors will not reimburse for standalone use.

“In my own personal thought process for patients with glaucoma, every single patient that has glaucoma that’s undergoing cataract surgery has some form of MIGS procedure performed on them,” says Mitchell C. Schultz, MD, FAAO, the cofounder and medical director of Schultz Chang Vision in Los Angeles.

Synergy Through MIGS Combinations

In recent years, some surgeons have reported encouraging results from performing two or more MIGS procedures, with complimentary mechanism of action, at the same time as cataract surgery. This allows surgeons to target multiple areas of resistance within the outflow system to get a better reaction. Proponents say that performing MIGS combinations often provides an optimal chance for significant IOP lowering while also reducing or eliminating the need for glaucoma medications.

“If I have my choice—if I have the freedom based on the patient’s insurance carrier—my choice is to basically dilate the drainage system and then place stents to get a greater effect,” says Dr. Shultz.

Over the past four years, Dr. Shultz has gathered data that supports this approach. He’s studied the effects of combining the iStent inject W (Glaukos) or the Hydrus Microstent (Ivantis) with ab interno canaloplasty utilizing the Omni Surgical System (Sight Sciences) or the iTrack Microcatheter (Nova Eye Medical) in patients with open-angle glaucoma who were undergoing concomitant phacoemulsification prior to cataract surgery. In some cases, in addition to canaloplasty and placing stents, Dr. Shultz also performed gonioscopy-assisted transluminal trabeculotomy (GATT). According to his data, patients in the combination MIGS groups experienced statistically significant reductions in both IOP and medication use through 12 months.^1,2

“I found that there was benefit and synergy from performing canaloplasty or dilating the trabecular meshwork and then placing stents, compared to each of those procedures independently, both for duration and for the number of patients we're able to get off of medication,” says Dr. Shultz.

Inder Paul Singh, MD, president of the Eye Centers of Racine and Kenosha in Wisconsin, says that he takes a similar approach. “Regardless of severity, if someone is on multiple medications to control IOP, my assumption is there is significant resistance in the conventional outflow system,” he says. “For instance, if someone has mild glaucoma but they’re on three or four medications, regardless of IOP, I’m going to hedge my bets and viscodilate the canal and collector channels and then address the TM by stenting or removal of tissue at the same time.”

Dr. Singh notes that the patient’s anatomy dictates his approach. A patient with peripheral anterior synechiae (PAS), a history of laser trabeculostomy, or an angle with a narrow approach may not be a good candidate for stenting. The decision of whether to place a stent also depends on indications, likelihood of distal collapse of the canal and/or outflow system, and severity level of resistance.

Reimbursement Challenges

Recent changes in reimbursement rates for MIGS devices make combining multiple procedures more financially viable for ambulatory surgical centers (ASCs), the cost of devices and surgeons’ comfort with performing the procedures affect the number of people who embrace combination MIGS, observes Dr. Schultz. “Reimbursement has certainly been a factor for people’s decision making, I think, in choosing stents versus goniotomy or canaloplasty,” he says. “For me, I feel there is definitely value to combining the two even though we don’t get reimbursed very much for the stenting. I think that it’s a disservice to the patients not to do it, and we definitely have seen very positive results from it.”

“When the iStent/Hydrus combination cataract code got changed to one single code, it brought the reimbursement down dramatically,” agrees Dr. Singh. “Medicare did not take into consideration all the time and effort it takes to place these devices. It’s a shame that they minimize the skill set that we need to learn do these procedures from start to finish and brought the reimbursement down so much. With that said, if the stent is the best thing to do for the patient, I will still utilize these technologies. There’s a value to stenting, and it is minimally invasive. Stents maintain high safety with minimal trauma to the target tissue, postoperative course is often similar to that of cataract surgery, and it keeps your options open.”

Surgeons are concerned that Medicare Administrative Contractors (MACs) seem to be pushing back on reimbursing for certain MIGS. In June, National Government Services, Noridian Health, Palmetto GBA, and Wisconsin Physician Services floated a draft local coverage determination (LDC) that would deem several MIGS procedures, including goniotomy and the combination of canaloplasty with trabeculectomy, to be investigational in patients over the age of 18.³

“I think it’s really a shame that Medicare and the MACs are pushing back and trying to accuse us of not having enough data,” says Dr. Singh. “We have clearly good data out there showing efficacy of goniotomies and canaloplasties. If we don’t get reimbursed for those procedures, that would really change the dynamic. That would be very disruptive and unfortunate for patients’ safety as well as for control of their glaucoma.”

New Products on the Horizon

Several new devices or approaches that may be nearing U.S. Food and Drug Administration (FDA) approval for use in the United States. Perhaps the closest to approval is iDose TR (Glaukos), an intraocular implant designed to continuously deliver travoprost, a prostaglandin analog (PGA), in order to reduce IOP in open-angle glaucoma or ocular hypertension. In the fall of 2022, the iDose TR achieved its prespecified primary efficacy endpoints in two phase 3 pivotal trials, and a successful phase 2b exchange trial was completed in January 2023. The FDA is processing the New Drug Application for iDose TR, with a prescription drug user fee act goal date of December 22, 2023.⁴

“I think the upcoming approval of the iDose is really going to change the paradigm,” says Dr. Singh, a Glaukos consultant who was one of the principal investigators for the phase 2 and phase 3 clinical trials of iDose. “When you’re doing a cataract-stent or cataract-goniotomy, or even a standalone MIGS procedure, you can also place this at the same time to get the PGA on board for a significant period of time. There is data out there showing efficacy of three years in some patients, so the longevity of that is impressive. This iDose provides us another option with complimentary mechanism action to get pressures down and reduce the drop burden.”

The Elios laser (Elios Vision) uses an excimer laser to create microchannels through TM into Schlemm’s canal. Excimer laser trabeculostomy (ELT) has been successfully performed in Europe since the late 1990s. In the United States, the Excimer Laser Trabeculostomy Glaucoma Treatment Study is currently ongoing under an FDA investigational device exemption. This prospective, multicenter clinical trial is intended to evaluate the safety and effectiveness of ELT to reduce IOP in 318 patients with primary open-angle glaucoma undergoing cataract surgery. The estimated study completion date is June 2025.⁵

Another laser device is the Direct SLT Eagle device (Belkin Vision), an automated, noncontact glaucoma laser treatment that works by administering 120 laser shots through the limbus to the trabecular meshwork using a proprietary algorithm and eye-tracking technology. The Eagle device received the CE Mark in May 2022.

Other Approaches

Several manufacturers are targeting the superciliary space once again. The original MIGS device that utilized this pathway, the CyPass Micro-Stent (Alcon), was approved by the FDA in 2016. Two years later, Alcon withdrew CyPass from the market after follow-up studies indicated a high rate of long-term endothelial cell loss.

To avoid this problem, a pair of newer devices have been made from materials that may be more easily tolerated in the eye than CyPass. The AlloPass (Iantek) is a soft biostent; a first-in-humans trial completed in 2023 reported a 40 percent drop in mean IOP from baseline and a 62 percent reduction in glaucoma medication use over 12 months.⁶

A second product, MINIject (iStar Medical) is a biocompatible silicon shunt implanted via an ab interno approach; it is available in Europe and is currently being investigated in a pivotal U.S. trial, STAR-V.⁷ Three previously completed MINIject trials found a 39 percent reduction in IOP over two years, with 38 percent of patients medication free and no safety concerns with corneal endothelial health, according to data presented at the ESCRS Congress in September 2022.⁸

Subconjunctival, minimally invasive bleb surgery (MIBS) technologies are also being developed. One of these is minimally invasive microsclerostomy (MIMS; Sanoculis), which uses a special surgical system and a disposable handpiece unit to remove a 90-μm diameter cylinder of scleral tissue, creating a drainage channel. The procedure has been approved in the European Union and Israel. Sanoculis hopes to initiate a pivotal clinical trial in the United States next year, and bring MIMS to the U.S. market in 2025.

Another company, Myra Vision, recently initiated a clinical trial to evaluate the safety and effectiveness of Calibreye, a titratable subconjunctival flow stenting system, in reducing intraocular pressure in subjects with POAG. The study is expected to be completed in April 2025.⁹ ■

References are available in the online version of this article.