January 24, 2020
American Glaucoma Society Position Paper:
Microinvasive Glaucoma Surgery (MIGS)
Ronald L. Fellman, MD1; Cynthia Mattox, MD2; Kuldev Singh, MD3; Brian Flowers, MD4; Brian A. Francis, MD, MS5; Alan L. Robin, MD6; Michelle R. Butler, MD1; Manjool M. Shah, MD6; JoAnn A. Giaconi, MD5; Arsham Sheybani, MD7; Brian J. Song, MD, MPH8; Joshua D. Stein, MD, MS6
1Glaucoma Associates of Texas, Dallas TX; 2Tufts University School of Medicine, Boston, MA; 3Stanford University, Palo Alto, CA; 4Ophthalmology Associates of Fort Worth, Fort Worth, TX; 5University of California – Los Angeles, Los Angeles, CA; 6University of Michigan, Ann Arbor, MI; 7Washington University, St. Louis, MI; 8Southern California Permanente Medical Group, Ontario, CA.
In 2018, the American Glaucoma Society (AGS), the world’s largest professional society of glaucoma subspecialists, convened a 12-member task force of experts to craft a Position Statement about Microinvasive Glaucoma Surgery (MIGS). The main objective of this Position Statement is to provide a succinct overview of these procedures and address some misconceptions about MIGS. The members of the task force were selected by the AGS Board of Directors and include AGS members with expertise in developing MIGS, teaching MIGS, performing research on utilization and outcomes of these procedures, and working with the U.S. Food and Drug Administration and other regulatory agencies about developing criteria to evaluate the efficacy and safety of these devices. Each of the sections of the Position Statement was prepared by subgroups of the task force and then the material from the various sections were aggregated and the leader of the task force (JDS) merged the material into a cohesive draft. This draft was shared with the AGS Executive Committee and other members of the AGS Board of Directors for additional input.
Overview and Definition of MIGS
Glaucoma is a group of chronic, often asymptomatic diseases that damage the optic nerve in a characteristic manner and, if left untreated or insufficiently treated, can lead to irreversible disability, vision loss, and blindness. In the United States, vision loss due to glaucoma is a leading cause of disability and blindness in blacks, whites, Latinos, and Asian Americans.1-4 The functional visual loss secondary to glaucoma is often measured by static automated perimetry and correlated with the degree of structural disc damage measured by optic disc photography and optical coherence tomography. Key objectives in the management of glaucoma are to maximize health-related quality of life, preserve remaining visual function, as well as minimize future vision loss and the risks of treatment necessary to achieve these goals.
Currently, the only known way of slowing the rate of glaucomatous vision loss is by lowering intraocular pressure (IOP). This can be achieved with medications, laser procedures, or incisional procedures. Medications are usually delivered as eye drops. While medications can be effective at lowering IOP, they can be expensive and difficult to administer. Nearly two-thirds of patients are unable to administer eye drops correctly and more than one-half of all patients with glaucoma struggle with medication adherence.5 Self-administration of eye drops can be quite difficult for many patients with glaucoma, and a large proportion of these patients live without a support structure to assist them.6,7 Moreover, a single class of IOP-lowering medication is inadequate to control the IOP in more than 50% of all patients with glaucoma.8 While it is possible to add additional classes of IOP-lowering medications, complex medication regimens frequently result in non-adherence, which in turn can lead to disease progression. Traditional incisional glaucoma procedures (i.e. trabeculectomy or aqueous shunt surgery) that create subconjunctival filtration blebs are often reserved for patients with progressive disease who are at high risk of severe vision loss. (Figure 1) These procedures can substantially lower IOP and preserve vision, but they themselves can decrease the quality of life and often require a lengthy recovery period, are subject to the vicissitudes of wound healing, and potentially have devastating complications.8-19 In recent years there has been a push for alternative surgical approaches to lower IOP that reduce the need for glaucoma medications and some of the serious risks associated with traditional glaucoma procedures, such as hypotony (low IOP), choroidal effusion and/or hemorrhage, tube exposure, bleb leaks, blebitis, and endophthalmitis. Collectively this new class of procedures is known as microinvasive glaucoma surgery (MIGS). MIGS procedures are designed to lower IOP by improving aqueous outflow with minimal disruption to the sclera or conjunctiva with or without an implanted device, or by reducing aqueous production selectively. Outflow enhancement can be accomplished by facilitating access of aqueous humor to Schlemm’s canal (canal-based), the suprachoroidal space, or the subconjunctival space. Reducing aqueous production can be accomplished through selective direct laser ablation of the ciliary processes, the structures that produce the aqueous humor.
Comparison of MIGS to Traditional Incisional Glaucoma Surgeries
All surgical procedures, including those for glaucoma, carry risks of adverse events. These risks must be carefully weighed against the expected benefits of preserving vision and quality of life. Many members of the AGS have enthusiastically supported the development of MIGS, particularly for the treatment of subsets of patients whose risk of vision loss from glaucoma progression may not justify the risk associated with traditional filtration surgery or aqueous shunt implantation. The non-trivial risk of vision loss associated with these traditional glaucoma procedures often outweighs the potential benefit of lowering IOP, discouraging ophthalmologists from recommending these procedures and patients from consenting for them except in relatively dire circumstances, even when they may help stabilize the disease.
Unlike traditional glaucoma procedures, canal-based MIGS can often be performed with smaller incisions, akin to those used during modern day cataract surgery. Most of these procedures enhance the physiologic outflow pathways of the eye, which results in a safer lowering of IOP. Patients with ocular hypertension who are at high risk for experiencing vision loss due to uncontrolled IOP or with early-stage glaucoma, but who cannot tolerate or afford medical treatment, might be excellent candidates for MIGS procedures. Likewise, patients with moderate- to severe-stage glaucoma whose ocular or medical comorbidities make them less than ideal candidates for traditional glaucoma surgery might also benefit. Fewer postoperative visits make these procedures excellent options for working-age patients and elderly patients who may rely upon working-age relatives to bring them to perioperative appointments.
Canal-based MIGS lower IOP by improving outflow through the patient’s natural drainage system instead of creating a bleb (a subconjunctival reservoir from which aqueous humor can slowly egress and thereby lower IOP) to capture the aqueous.20 This considerably enhances the safety profile and limits discomfort, which can be an issue with traditional glaucoma procedures. Patients who are deemed to not be good candidates for canal-based MIGS may still be candidates for subconjunctival MIGS, a less invasive form of classic filtration surgery that utilizes microstents to create a bleb.20,21 Other potential advantages of MIGS over traditional glaucoma procedures include faster recovery, less impact on leisure activities (such as swimming), and reduced risk of damaging other structures in the eye that can necessitate additional ocular surgeries. While many patients with different types and severities of glaucoma can benefit from MIGS, some patients clearly fare better with traditional glaucoma filtration surgery, so it is important to have all of these procedures available to allow the surgeon and patient together to decide which intervention is most appropriate.
Categorization of Different MIGS Procedures
Most MIGS lower IOP by reducing outflow resistance. To accomplish this, the surgeon may dilate, cleave open, or bypass abnormally resistant tissue that is hindering outflow or insert a device into an outflow structure or space to enhance the drainage of aqueous. These procedures may be divided broadly into bleb-forming and non-bleb-forming procedures.20 Bleb-forming MIGS are placed through an ab-externo (outside of the eye) or ab-interno (inside of the eye) approach while all non-bleb forming MIGS are performed ab-interno. These devices may be further categorized based on the anatomical location of device placement or tissue manipulation. This categorization aligns with Current Procedural Terminology (CPT-4) coding as outlined in Figure 1.
Complexity of MIGS Procedures
In general, intraocular surgery is a complex task as it involves working in very small spaces, adjacent to sensitive structures, where missteps can lead to permanent vision loss. The learning curve can be quite long and difficult. Residency and fellowship training forms the basis of the acquisition of these skills. Performing MIGS requires an even higher skill level as it requires the use of gonioprism mirrors under an operating microscope to visualize the ocular structures that require treatment, working in even smaller more sensitive spaces within the eye, and requires learning a new proprioceptive skill, namely intraoperative surgical gonioscopic viewing of the angle. This particular skill requires more manual dexterity as the surgeon must use one hand to balance the gonioprism on the cornea to permit visualization of the structures requiring treatment and simultaneously the second hand to carry out the procedure. Although gonioscopy is used to classify and diagnose glaucoma at the slit lamp in all patients with glaucoma, the skills required at the surgical microscope are usually more difficult to master. Those with experience training new surgeons in these techniques have observed that some new surgeons can adapt to these increased demands, but many cannot. It may seem paradoxical that a safer surgical procedure with fewer complications tends to require more manual dexterity involving both hands simultaneously, better anatomic knowledge, and be more technically demanding to perform. However, this is actually relatively common in medicine as evidenced in the transition from open to laparoscopic surgery and the transition from intracapsular cataract surgery to extracapsular cataract surgery to phacoemulsification.
As with any surgical procedure, a prerequisite to the success of MIGS involves a thorough preoperative assessment to ensure the patient is an appropriate candidate for a given procedure, to select which procedure is most likely to succeed for a particular patient, and to be certain that the benefits of the surgery outweigh its risks. There are many nuances of these surgeries that must be considered to achieve optimal results. For example, careful examination of the anterior chamber angle is of paramount importance. If a MIGS procedure is combined with cataract surgery, it is also very important to evaluate for conditions that may increase the complexity of the surgery such as peripheral anterior synechiae, conjunctival scarring, angle visibility, and zonular instability. In addition, determining the site from which to approach a given procedure, for example ab interno or ab externo, requires careful consideration, as it may affect the options available for subsequent glaucoma surgery. Another preoperative consideration is the provision of thorough informed consent to the patient. During such a discussion, the surgeon should acknowledge the fact that long-term outcomes for many MIGS procedures are not yet known and there may be unanticipated risks associated with these surgeries.
The postoperative period after some MIGS procedures is generally much easier on patients than after traditional glaucoma surgeries. Discomfort from conjunctival sutures is less frequent (since sutures are not needed for many MIGS) and visual recovery tends to be quicker than with traditional incisional glaucoma procedures. However, careful postoperative care is still required to achieve good outcomes as patients undergoing MIGS are more prone to postoperative complications such as IOP spikes, device movement or erosion, hyphema, and corticosteroid-induced elevation of IOP relative to other patients who undergo cataract surgery alone.22 As such, it is important to educate the patient of the importance of postoperative care, to help ensure the success of the procedure.
Considerations for Clinical Trial Design for MIGS
There is no one ideal therapeutic approach that applies to every patient with glaucoma. Glaucoma therapy must be tailored based upon weighing the risk and benefit of the various treatment options, taking a patient’s disease state and projected course into careful consideration. Given the variability in the effectiveness, safety profile, patients’ responses to different therapies, and patients’ perceptions of the relative importance of the various risks and benefits, glaucoma care very much remains a mixture of art and science.
“Maximum tolerated medical therapy” and “refractory glaucoma” are ambiguous terms that may be confusing when integrated into clinical practice guidelines and policy statements. Differences in interpretation of these terms can also result in ambiguity in determining patients who may be eligible for different MIGS procedures. To help provide clarification, the AGS defines the terms as follows:
“Maximum tolerated medical therapy” (MTMT) is attained once the patient is successfully using the greatest number of topical glaucoma medication classes he or she can tolerate and that add additional IOP reduction. For some patients that could be as many as 6 or more different classes of glaucoma medications taken daily, and for others it is no medications at all. Medication intolerance can be attributed to a variety of reasons ranging from expense, side effects, and an inability to administer eye drops. As mentioned earlier, non-adherence to glaucoma medications for any of the above reasons can cause permanent vision loss as the disease progresses. In some patients, the clinical presentation is so severe that incisional surgery is the most appropriate initial intervention, even forgoing medical treatment.
“Refractory glaucoma” is simply glaucoma that is difficult to treat and poorly controlled by current therapy, regardless of the stage of disease. Stage of disease as defined in the literature and based on the ICD-10 coding system designates the amount of damage to the visual system from glaucoma at a moment in time. All patients have a risk of progressing to worsening stages of glaucoma damage over time if their glaucoma is not controlled. There are a variety of reasons why a particular patient’s glaucoma may be difficult to treat, ranging from an inability to properly adhere to the medical management plan, inability to instill eye drops, poor responsiveness of the eye to IOP-lowering interventions, systemic side effects, or the presence of scar tissue from prior injury or surgery.
Historically, treatment options have involved topical medications and laser trabeculoplasty for patients with mild to moderate disease. Riskier surgical approaches are usually reserved for those with more advanced glaucoma, those who are at higher risk of losing visual function, or who fail less invasive options. There has been a large void with regard to surgical options for patients who are unable or unwilling to take glaucoma medications, and for those with mild yet progressive disease in whom medications and laser fail to sufficiently control IOP, but the disease severity level does not justify the inherent risks of traditional incisional glaucoma surgery. The availability of MIGS devices has afforded more therapeutic options to address this large segment of patients with glaucoma. The FDA and the AGS have since come together for workshops and discussions to advance these innovations to serve patients with glaucoma. Unfortunately, given the absence of an appropriate predicate device, the FDA premarket approval pathway (PMA) for many implantable MIGS devices has been very expensive, time consuming, and sometimes frustrating for researchers and companies trying to innovate in this area. In the case of ab interno MIGS implants, the devices were required by the FDA to be implanted at the time of concomitant cataract surgery. This was partly to investigate the IOP-lowering effect of cataract surgery alone in a control population, but also as a way to mitigate risk as recipients of the implants received the benefit of cataract surgery. Hence clinical indications on the labels for the ab interno implants all specify “with cataract surgery.” Another example applies to the “bleb-forming” MIGS, for which there are 3 ongoing trials (with more anticipated soon) of stand-alone MIGS procedures underway with the Ahmed (New World Medical Inc., Fontana, CA) glaucoma drainage device, a traditional glaucoma filtration surgery device, as the predicate device. Unfortunately, the study samples for these trials are required to be similar to those used in trials involving the predicate device. As such, these trials must be performed on patients labeled with “refractory glaucoma,” which has previously been defined by other groups as those that have failed at least one incisional glaucoma surgery. Yet the intended population who could most benefit from many MIGS surgeries is actually quite different from those who have already undergone incisional glaucoma surgeries. This study design with the requirement of failed prior surgery can greatly affect the results of the trial and create a potentially flawed process for evaluating these devices. The AGS recommends the FDA use the “de novo” (or other similar or novel) pathway for evaluating glaucoma devices with known (or anticipated) high levels of safety, such as most MIGS procedures. The AGS welcomes the opportunity to work with the FDA to develop appropriate protocols for trials and work through other logistical considerations to permit new MIGS devices to be evaluated in a fair manner on groups of patients with glaucoma who would better align with the intended target population when such devices are approved for marketing.
The AGS believes that as data accumulate from completed PMA studies for various MIGS, there needs to be greater flexibility with respect to expanding the indication of already approved devices. Furthermore, the introduction of next generation MIGS devices (where prior data is undoubtedly useful, particularly with regard to safety) should not be a static process but instead should permit developers of these devices the flexibility of the 510K pathway for “refractory glaucoma”. There are several different approaches that could allow for such flexibility. One option would involve redefining and expanding the criteria for what constitutes “refractory glaucoma” for purposes of the regulatory process, the same way that AGS defines this condition, as described above. Another option would be to create a parallel 510K pathway with previously approved MIGS device as a historical predicate, as noted in the aforementioned paragraph. We believe that regulatory authorities should engage the AGS, either via the existing network of experts, or via other formal associations, to outline the appropriate clinical trial designs necessary for clearance of the next generation of MIGS devices, as well as for expansion of indications for already approved devices.
In contrast to other regions in the world, regulatory decisions in the United States have historically been separated from those related to reimbursement. The AGS believes that patients and their doctors might be better served if the information gathered by regulatory authorities in the clearance and labelling of innovative products (such as MIGS) was readily available to the authorities that make determinations about reimbursement. This could expedite the availability of these less invasive micro-incisional devices to patients for whom they would be beneficial. A related issue that often limits patients’ access to these MIGS procedures is that payors may only permit patients to undergo these procedures if they precisely fit the profile of those who received such a procedure during the FDA approval process. For example, because most of FDA trials involving MIGS have been performed on patients receiving these devices in combination with cataract surgery, several payors will only approve reimbursement of these procedures in patients who receive them concurrently with cataract surgery, despite the additive IOP-lowering effect of the implants observed in the clinical trials. This can be very problematic, especially for patients who either have no cataract or have already had their cataracts removed but might still benefit from these MIGS devices as stand-alone procedures.
With the rapidly rising number of patients with glaucoma in the United States and worldwide, it is essential for researchers and industry to continue developing innovative therapeutic options that are effective at lowering IOP, possess a good safety profile, and are well tolerated by patients. The advent and evolution of MIGS has increased the therapeutic options for patients with glaucoma, but there is still considerable room for improvement in the surgical delivery of glaucoma care. The AGS supports efforts that facilitate patient access to these procedures and that permit the clinician and patient to jointly decide which intervention(s) along the entire spectrum of care are best for them based on their unique circumstances.
- Friedman DS, Wolfs RC, O'Colmain BJ, et al. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol. 2004;122(4):532–538.
- Quigley HA, West SK, Rodriguez J, Munoz B, Klein R, Snyder R. The Prevalence of Glaucoma in a Population-Based Study of Hispanic Subjects: Proyecto VER. Arch Ophthalmol. 2001;119(12):1819–1826.
- Varma R, Wang D, Wu C, et al. Four-year incidence of open-angle glaucoma and ocular hypertension: the Los Angeles Latino Eye Study. Am J Ophthalmol. 2012;154(2):315–325.e1.
- Stein JD, Kim DS, Niziol LM, et al. Differences in rates of glaucoma among Asian Americans and other racial groups, and among various Asian ethnic groups. Ophthalmology. 2011 Jun;118(6):1031-7.
- Hennessy AL, Katz J, Covert D, et al. A video study of drop instillation in both glaucoma and retina patients with visual impairment. Am J Ophthalmol. 2011;152(6):982–988.
- Tsai T, Robin AL, Smith JP3rd. An Evaluation of how Glaucoma Patients use topical medications: A Pilot Study. Trans Am Ophthalmol Soc. 2007;105:29-33; discussion 33-5.
- The Advanced Glaucoma Intervention Study (AGIS): 3. Baseline characteristics of black and white patients. Ophthalmology. 1998 Jul;105(7):1137-45.
- Musch DC, Gillespie BW, Niziol LM, Lichter PR, Varma R; CIGTS Study Group. Intraocular pressure control and long-term visual field loss in the Collaborative Initial Glaucoma Treatment Study. Ophthalmology 2011;118:1766-1773.
- Gedde SJ, Heuer DK, Parrish RK 2nd; Tube Versus Trabeculectomy Study Group. Review of results from the Tube Versus Trabeculectomy Study. Curr Opin Ophthalmol. 2010 Mar;21(2):123-8.
- Fontana H, Nouri-Mahdavi K, Lumba J, Ralli M, Caprioli J. Trabeculectomy with mitomycin C: outcomes and risk factors for failure in phakic open-angle glaucoma. Ophthalmology. 2006 Jun;113(6):930-6.
- Kim HY, Egbert PR, Singh K. Long-term Comparison of Primary Trabeculectomy With 5-Fluorouracil Versus Mitomycin C in West Africa. J Glaucoma. 2008 Oct-Nov;17(7):578-83.
- Wong MH, Husain R, Ang BC, Gazzard G, Foster PJ, Htoon HM, et al. The Singapore 5-fluorouracil trial: intraocular pressure outcomes at 8 years. Ophthalmology. 2013 Jun;120(6):1127-34.
- Robin AL, Ramakrishnan R, Krishnadas R, Smith SD, Katz JD, Selvaraj S et al. A long-term dose-response study of mitomycin in glaucoma filtration surgery. Arch Ophthalmol. 1997 Aug;115(8):969-74.
- Jampel H. Trabeculectomy: more effective at causing cataract surgery than lowering intraocular pressure? Ophthalmology. 2009 Feb;116(2):173-4.
- Wong TT, Khaw PT, Aung T, Foster PJ, Htoon HM, Oen FT, et al. The singapore 5-Fluorouracil trabeculectomy study: effects on intraocular pressure control and disease progression at 3 years. Ophthalmology. 2009 Feb;116(2):175-84.
- Stein JD, Ruiz D Jr, Belsky D, Lee PP, Sloan FA. Longitudinal rates of postoperative adverse outcomes after glaucoma surgery among medicare beneficiaries 1994 to 2005.
Ophthalmology. 2008 Jul;115(7):1109-1116.
- Palanca-Capistrano AM, Hall J, Cantor LB, Morgan L, Hoop J, WuDunn D. Long-term outcomes of intraoperative 5-fluorouracil versus intraoperative mitomycin C in primary trabeculectomy surgery. Ophthalmology. 2009 Feb;116(2):185-90.
- Shigeeda T, Tomidokoro A, Chen YN, Shirato S, Araie M. Long-term follow-up of initial trabeculectomy with mitomycin C for primary open-angle glaucoma in Japanese patients. J Glaucoma. 2006 Jun;15(3):195-9.
- Gedde SJ, Herndon LW, Brandt JD, Budenz DL, Feuer WJ, Schiffman JC; Tube Versus Trabeculectomy Study Group. Postoperative complications in the Tube Versus Trabeculectomy (TVT) study during five years of follow-up. Am J Ophthalmol. 2012 May;153(5):804-814.
- Schehlein EM, Kaleem MA, Swamy R, Saeedi OJ. Microinvasive Glaucoma Surgery: An Evidence-Based Assessment. Expert Rev Ophthalmol. 2017;12(4):331–343.
- Chatzara A, Chronopoulou I, Theodossiadis G, Theodossiadis P, Chatziralli I. XEN Implant for Glaucoma Treatment: A Review of the Literature. Semin Ophthalmol. 2019;34(2):93-97.
- Yook E, Vinod K, Panarelli JF. Complications of micro-invasive glaucoma surgery. Curr Opin Ophthalmol. 2018 Mar;29(2):147-154.
Fellman: Consultant: Alcon, Beaver Visitech Inc.; Honorarium: Aerie, Bausch and Lomb; Research support: Ivantis, Glaukos; Mattox: Consultant: Aerie, Alcon, Allergan, Glaukos, Ivantis, New World Medical, Santen, Zeiss Meditec; Singh: Consultant: Alcon, Allergan, Glaukos, Ivantis, Santen, Sight Sciences; Flowers: Consultant: Alcon, Ivantis, Sun Pharmaceuticals, Bausch and Lomb, InnFocus, Sight Science, New World Medical, iStar, EyeNovia. Research support: Alcon, Ivantis, Glaukos, Aerie, InnFocus, Sight Science, iStar, Santen; Francis: Consultant: Neomedix, Glaukos, Beaver Visitech; Research Support: Santen, Allergan, iStar; Speaker: Aerie, Bausch and Lomb; Robin: Consultant: Google AI; Butler: Speaker: Allergan; Shah: Consultant: Allergan, Glaukos, Katena; Speaker: Allergan; Giaconi: Speaker: Allergan; Sheybani: Consultant: Allergan, Katena, Ivantis; Speaker: Glaukos, Allergan
Song: None; Stein: None