Over the past 2 decades, new devices and surgical techniques designed to lower intraocular pressure (IOP) and reduce the need for glaucoma medications have emerged as useful tools in the surgeon’s armamentarium. Collectively known as minimally invasive (or microinvasive) glaucoma surgery (MIGS) procedures,¹ these sight-preserving surgical treatments for glaucoma reduce or eliminate abnormal resistance to aqueous humor outflow from the anterior chamber. MIGS have proven to be legitimate alternatives to more extensive traditional procedures like trabeculectomy or glaucoma drainage device (GDD) implantation, spawning debates² and spurring excitement and considerable investment.

“I think there had long been an interest in finding alternative approaches to glaucoma surgery that did not involve jumping to the biggest guns that we have,” says Matthew E. Emanuel, MD, a glaucoma specialist at the Glaucoma Associates of Texas in Dallas, who adds that learning about the initial MIGS procedures during his residency attracted him to the field of glaucoma. “The emergence of MIGS has reinvigorated the field, not only for glaucoma specialists but also for comprehensive ophthalmologists, who use them quite a bit. I found it exciting that suddenly, rather than taking a one-size-fits-all approach, we could pursue new options that would allow us to tailor our patients’ care.”

It was also during her residency that Cindy Zheng, MD, a cataract surgeon and glaucoma specialist at the Wills Eye Hospital in Philadelphia, first encountered MIGS.

“I first learned about MIGS procedures in 2012, just after the FDA approval of the iStent,” says Dr. Zheng. “The introduction of MIGS was a very exciting time for our field because for a long time, glaucoma specialists had only traditional trabeculectomy, glaucoma drainage device surgery, and cyclophotocoagulation to lower intraocular pressure. Now, we have a vast armamentarium of options, which ultimately can help improve patient outcomes, when the tools are used in the right way.”

Although the position of MIGS in the glaucoma treatment paradigm will continue to undergo refinements, these novel procedures are expected to continue to revolutionize the field in coming decades.

The Current Landscape

The number of MIGS devices that have been approved for use by the US Food and Drug Administration (FDA) continues to rise.³ All of the devices (Table 1) meet the current definition of MIGS in the United States, which was jointly developed by the FDA and the American Glaucoma Society, and defined as procedures and devices that lower intraocular pressure (IOP) by increasing the aqueous humor outflow by means of an ab interno or ab externo approach, with limited (if any) dissection of the sclera and minimal (if any) manipulation of the conjunctiva. Although many specialists today tend to think of the iStent as the original MIGS device, the Trabectome, which appeared in 2006, was technically the first MIGS device to be developed.

“One problem with the term ‘MIGS’ is that it includes a heterogeneous group of surgical devices and procedures, some of which may not be truly minimally invasive. When speaking about MIGS it is best to clarify which device or procedure, rather than lumping them into one category,” says Yvonne M. Buys, MD, FRCSC, a professor in the department of ophthalmology and vision sciences at the University of Toronto in Canada. “As newer technologies become available, the definition of a MIGS device or procedure may change. The Trabectome has indeed been called a MIGS by most, and I would keep it in this category, though it is not an implanted device. My impression is that the popularity of the Trabectome has decreased, partly because of the technical requirements for performing the procedure, which are more considerable than those for an iStent. Cost may also be an issue. Because iStents are done at the time of cataract surgery, there are more opportunities for using this procedure.”

Of the MIGS devices that have been approved to date, only 1 has been withdrawn from the market.

“Alcon voluntarily withdrew Cypass from the market due to concerns related to corneal endothelial cell loss, which could lead to corneal failure and require surgery to repair,” says Dr. Buys. “It is possible that a new iteration could be released in the future. This device drained into the supraciliary space, so it avoided the creation of a bleb. Although bleb-forming procedures to date are the most efficacious for lowering intraocular pressure, blebs are associated with side effects ranging from discomfort, or bleb dysesthesia, to infection and vision loss.”

Evolving definitions of MIGS may eventually comprise subcategories. Pereira and colleagues have noted, for example, that in contrast to other MIGS strategies, those that involve the subconjunctival route are “fundamentally nonphysiological” because aqueous humor does not flow naturally into the subconjunctival or sub-Tenon’s space.¹ In their 2021 publication, these authors described and provided illustrations for 2 subconjunctival MIGS devices: the Xen gel stent (Allergan/AbbVie) and the Preserflo MicroShunt (Santen). The former device was approved in the United States in 2016, while the latter device continues to undergo clinical trials.

“Among the studies that I’m following now are those for Preserflo MicroShunt device,” says Dr. Zheng. “One of the main issues in glaucoma is scarring, and most of our surgeries are focused on reducing scarring around our drains so that they continue to work in the long term. The Preserflo has a material that is used in cardiac stents, which should theoretically be less likely to scar. In addition, it has a larger lumen (70 μm) than the Xen (45 μm), so there’s more outflow and IOP reduction, though there is a higher risk of overflow if not used correctly. Recent studies published within the past year looking at 2-year outcomes of the Preserflo MicroShunt are promising.”

Still a Role for Conventional Procedures

The emergence of MIGS represents an expansion of options, rather than a true paradigmatic shift in the approach to glaucoma surgery, because MIGS are unlikely to replace the need for conventional procedures and devices entirely.

“The vast majority of the MIGS surgeries work on the patient’s natural drainage system for the eye — that is, the trabecular meshwork or Schlemm’s canal,” says Dr. Emanuel. “But patients with certain types of glaucoma who don’t have any functioning drainage system, or have a system that cannot be made functional, are not typically MIGS candidates. One example would be neovascular glaucoma, in which abnormal blood vessels grow in the eye, blocking the drainage system and rendering it nonfunctional. Other patients include those who have failed prior MIGS surgeries. And of course, some MIGS procedures are FDA approved to be done only with cataract surgery, so patients who have already had cataract surgery don’t qualify for those procedures. Overall, there is still a place — a large place — for traditional surgeries.”

“The trabeculectomy is still considered the gold standard,” says Dr. Zheng. “Although MIGS are being used more often now, there are limits to their effects. For example, most MIGS procedures have been shown to reduce IOP by only 2 mmHg to 5 mmHg, depending on the device. If a patient fails to reach their IOP goal after cataract surgery with MIGS, then they may need a trabeculectomy as their next surgical step. Although MIGS are less invasive than traditional trabeculectomy or glaucoma drainage devices, they should be used in appropriate clinical scenarios. MIGS are a great adjunct to cataract surgery and help lower IOP, but there are still many patient situations that call for a trabeculectomy or glaucoma drainage device.”

For now, the IOP-reducing ability of conventional surgeries is still superior, but experts agree that clinical decision-making must take into consideration patient values and preferences.

“Though some of the MIGS available now may not be as effective as traditional surgeries at lowering IOP, there are some cases in which we may be willing to have less success for less risk,” says Dr. Emanuel. “Not everyone needs a home run. If we have a patient for whom we’ve set a target pressure in the low teens or single digits, a traditional glaucoma surgery might be best for that patient and have a higher chance of succeeding. But many patients do fine with pressures in the mid or upper teens, or even in the low 20s. So, if that is your target range, why use the most invasive surgery you have? Why not select something that is less invasive, involves a quicker recovery, and has less risk of morbidity for the patient? A MIGS procedure in that situation will likely achieve your goal, but also leave open the option to do a more traditional surgery later, if the patient should need it.”

Comparing Devices and Techniques

In 2019, the AAO published a study that examined the degree to which MIGS clinical trials conform to the World Glaucoma Association (WGA) guidelines for surgical trials.⁴ The study was prompted by a lack of well-designed MIGS studies, which has hindered and continues to hinder meaningful evaluation of these newer technologies. The study’s investigators found that published comparative MIGS trials proved to have a low adherence (45.6%) to WGA guidelines. The investigators concluded that there was a significant need for the development of standardized methodology and outcomes for all MIGS-related trials, to enhance both the interpretation and transparency of study results and facilitate comparisons between trials.

In 2020, Dr. Buys and colleague David Mathew, MBBS, PhD, published a critical appraisal of MIGS literature, in which they analyzed the advantages and limitations of various MIGS and examined the relative position of MIGS in the glaucoma treatment paradigm.³ Their study is notable not only for its detailed examination of available literature but also for its examination of ethical issues, including those related to author conflicts of interest and industry funding. The authors concluded that there continues to be insufficient evidence available for comparing the efficacy and safety of the various MIGS. They recommended further study of MIGS, including long-term studies that might assess efficacy, long-term complications, and costs of implanted devices, and studies that will enable better and more transparent reporting of results, with meaningful endpoints.

Better economic assessments of MIGS also will be necessary to provide physicians, policy makers, and patients with the information necessary to properly evaluate costs and benefits for each new intervention. Ultimately benefit-cost analyses will be important for improving patient access to MIGS.

“Unfortunately, insurance coverage is one of the biggest challenges we face,” says Dr. Emanuel. “Newer procedures, even if FDA approved, can be declined because they are still considered experimental when compared with more traditional procedures, and there might not always be the logic that we would hope for when a decision is considered. I’m often on the phone explaining why a MIGS procedure would be safer and plenty effective and, most importantly, in a patient’s best interest. But if an insurer decides to categorize the procedure as experimental, then our hands are tied. It’s unfortunate because these decisions can hinder patient access to some fantastic devices and surgical options.”

Training Residents

Glaucoma surgical training is an important part of the resident experience in ophthalmology, and the Accreditation Council for Graduate Medical Education (ACGME) currently requires residents to perform a minimum of 86 cataract extractions and 5 glaucoma surgeries, with each resident performing a minimum number of glaucoma procedures as primary surgeon. Surgical instruction for a growing number of novel procedures, such as those involving MIGS, typically parallels surgical trends observed in Medicare data. Because of the popularity of the iStent in recent years, for example, many resident training programs teach its implantation, although this procedure is not yet formally required by ACGME for residency graduation. However, because of concerns about the proficiency of novice surgeons, there is a persistent need for studies that report outcomes for newer glaucoma surgical procedures performed by residents and compare them with outcomes of those performed by experienced glaucoma specialists.

“One of my primary areas of interest is resident teaching,” explains Dr. Zheng, “so I’ve worked on a study comparing outcomes of iStent procedures performed by residents with those performed by attending surgeons. Our research study found that the decrease in IOP and number of medications required at the final follow-up was similar when comparing resident-performed cases with attending-performed cases. There was a similar safety profile between the 2 groups as well.”

The study by Zheng et al involved a retrospective review of all records of patients who had microbypass stent surgery performed by a resident at Wills Eye Hospital.⁵ The attending-performed group included any case involving a patient who had a microbypass stent implanted by an attending surgeon on the same day that a resident case was performed.

“At the time that our study was forming in 2014,” says Dr. Zheng, “there were very few residency programs that were allowing residents to perform iStents, since the stent was only released 2 years prior. The goal of our study was to see how well residents performed in comparison to attendings. We expected that resident-performed iStents would have similar outcomes and safety profiles to attendings, and our study was able to show that. Resident training programs across the country have very different levels of MIGS exposure, and there is definitely a need for more resident-based studies. If we can show that MIGS procedures are effective and safe, even in resident hands, it may encourage faculty to collaborate on more cases with residents.”

Sharing Experiences

Currently, guidelines for the use of MIGS have yet to be developed. For now, glaucoma specialists are gathering valuable personal and clinical experience, and in some cases reserving judgment for particular procedures until more data can be collected.

“I don’t have a particular MIGS surgery that I always do,” says Dr. Emanuel. “I am willing to try just about everything, and that includes procedures that are already FDA-approved as well as those undergoing the multiple clinical trials that our practice is involved in. I think our patients deserve it. When it comes to selecting a procedure there are many factors to consider. The age of the patient matters, the number of years that the patient has had glaucoma matters, race and family history matter. So, I remain open to trying new procedures because that is how we move the field forward.”

As specialists gain expertise with MIGS, they also depend on learning from the wisdom and experience of their colleagues.

“There is a definite need to discuss clinical experiences and suggestions with colleagues,” says Dr. Zheng. “Medicine is not practiced in isolation. There are challenging cases that may require input from colleagues, to come up with the best approach for tackling these cases. There are multiple forums for ophthalmologists and especially glaucoma specialists, for discussing their experiences or offering insight on challenging cases, through AAO, the American Glaucoma Society (AGS), and even Facebook. I’ve personally used all these forums and they’ve been helpful.”

“I am very lucky to be in a practice that has many people who do exactly what I do,” says Dr. Emanuel, “so my number one forum involves bouncing ideas off my colleagues at my practice. All 8 of us frequently discuss cases and arrive at different options for our patients, and often patients can even hear us discuss various options, which I think can be very beneficial for a patient. On a larger, more global scale, in addition to AAO and AGS, the American Society of Cataract and Refractive Surgery also has forums for MIGS discussions, because comprehensive ophthalmologists are doing a lot of these procedures these days. In general, MIGS have been widely adopted — they are not procedures only performed by a tiny group of specialists.”

Dr. Emanuel adds that in some forums, there can be pushback to MIGS — for example, from surgeons who only perform trabeculectomies and tube shunt surgeries and consider MIGS ineffective or a fad that will pass with time. “I think that pushback can be good,” he says. “It encourages people to gather data and publish reports that demonstrate the value of these procedures.”

Guidelines, which may be on the horizon, could be useful if they don’t prove to be too restrictive. “I think it would be helpful to have more studies comparing the various MIGS,” says Dr. Emanuel. “Unfortunately, such studies may not necessarily be profitable for the device makers, particularly if a study were to result in an unfavorable comparison with a competing device. Guidelines could come in handy if they led to evidence supporting the use of a particular MIGS in a particular patient scenario.” The downside, he says, would be if guidelines turned into requirements. “There are too many factors that go into a clinical decision for a particular patient, and there are only a very limited number of factors that any single study can examine. I’m a strong believer in clinical trials and the data they can provide, but guidelines must leave room for the practitioner to use his or her best clinical judgment in unique patient situations.” GP

References

1. Pereira ICF, van de Wijdeven R, Wyss HM, Beckers HJM, den Toonder JMJ. Conventional glaucoma implants and the new MIGS devices: a comprehensive review of current options and future directions. Eye (Lond). 2021;35(12):3202-3221. doi:10.1038/s41433-021-01595-x
2. Bloom P, Au L. “Minimally invasive glaucoma surgery (MIGS) is a poor substitute for trabeculectomy”—the great debate. Ophthalmol Ther. 2018;7(2):203-210. doi:10.1007/s40123-018-0135-9
3. Mathew DJ, Buys YM. Minimally invasive glaucoma surgery: a critical appraisal of the literature. Annu Rev Vis Sci. 2020;6:47-89. doi:10.1146/annurev-vision-121219-081737
4. Mathew DJ, McKay BR, Basilious A, Belkin A, Trope GE, Buys YM. Adherence to World Glaucoma Association guidelines for surgical trials in the era of microinvasive glaucoma surgeries. Ophthalmol Glaucoma. 2019;2(2):78-85. doi:10.1016/j.ogla.2019.01.007
5. Zheng CX, Copparam S, Lin MM, et al. Outcomes of trabecular microbypass surgery: comparison of resident trainees and attending surgeons. J Cataract Refract Surg. 2019;45(12):1704-1710. doi:10.1016/j.jcrs.2019.07.021