Micro-Invasive Glaucoma Surgery (MIGS)

Title XVIII of the Social Security Act, §1862 (a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

Title XVIII of the Social Security Act, §1862 (a)(1)(D) indicates no payment may be made in the case of clinical care where items and services provided are in research and experimentation.

CMS Internet-Only Manual, Pub 100-02, Medicare Benefit Policy Manual, Chapter 14, §10 Coverage of Medical Devices

CMS Internet-Only Manual, Pub 100-08, Medicare Program Integrity Manual, Chapter 13, §13.5.3 Evidentiary Content and §13.5.4 Reasonable and Necessary Provisions in LCDs

Background

Primary open-angle glaucoma (POAG) has a prevalence in the US of 2% of adults over 40 years old, or about 2.2 million people and is expected to increase to 3.3 million in 2020 as the population ages.¹ POAG is a chronic, progressive optic neuropathy in adults in which there is a characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons. It is associated with an increased intraocular pressure (IOP) due to a buildup of aqueous fluid within the eye which can lead to visual field loss and optic nerve damage, usually without any associated pain or discomfort. The increased IOP is secondary to an imbalance between aqueous fluid secretion and fluid outflow despite an open angle. Nearly 40% of those with otherwise characteristic POAG may not have elevated IOP measurements.¹ 

In the primary (conventional) outflow pathway from the eye, aqueous humor passes through the trabecular meshwork, enters a space lined with endothelial cells (Schlemm's canal), drains into collector channels and then into the aqueous veins. Increases in resistance in the trabecular meshwork or the inner wall of the Schlemm's canal can disrupt the balance of aqueous humor inflow and outflow, resulting in an increase in IOP and glaucoma risk.

The goal in POAG is to reduce the IOP to slow the development of optic nerve damage. The IOP can be reduced by medical treatment or surgery, alone or in combination. IOP above 21 mmHg has been shown to increase rates of visual field loss. However, because of the differences in susceptibility to pressure-related disc damage among POAG patients, pressure-lowering treatments are aimed at achieving a lower “target” pressure individualized to each patient’s baseline IOP in which glaucomatous damage occurred.

When the maximum tolerated medical therapy fails to control progression of glaucomatous optic neuropathy, surgical care is considered the next treatment option. Traditional filtration surgery includes trabeculectomy (including Express^® shunt) and aqueous drainage implants (Ahmed, Baerveldt, Molteno). Trabeculectomy uses the patient’s own sclera to create a fistula to the subconjunctival space over the sclera. Aqueous drainage implants use silicone/plastic tubing and large plates to shunt aqueous humor to the subconjunctival space in the equatorial region of the eyeball.

While IOP outcomes are generally worse with aqueous drainage implants compared with trabeculectomy, complications such as hypotony (low pressure) and postoperative infection are reduced. However, failure rates are similar (approximately 10% of devices fail annually) and shunts still have complications, including corneal endothelial failure and erosion of the overlying conjunctiva.

The term micro-invasive or minimally invasive glaucoma surgery (MIGS) refers to a group of newer surgical procedures that are performed by using an ab interno (from inside the eye) approach via gonioscopic guidance and involve minimal trauma to ocular tissues. In contrast to external filtration surgeries such as trabeculectomy and aqueous tube shunt, these procedures are categorized as internal filtration surgeries. Compared with traditional filtration surgery, MIGS holds the promise of faster recovery time and less severe complications.

It is this potentially improved safety profile that opened up the indications for MIGS to include patients with early-stage glaucoma to reduce the burden of medications and problems with compliance (due to eye drop application difficulty, cost, cosmetic effects and frequency). Another area of investigation is patients with glaucoma who require cataract surgery. An advantage of ab interno shunts is that they may be inserted into the same incision and at the same time as cataract surgery. In addition, most devices do not preclude subsequent trabeculectomy if needed. Therefore, health outcomes of interest are the IOP achieved, reduction in medication use, ability to convert to trabeculectomy, complications and device durability.

There are 4 Food and Drug Administration (FDA) approved/cleared micro-invasive surgical stents, the iStent^® Trabecular Micro-Bypass Stent (2011), the XEN^® Glaucoma Treatment System (November, 2016), the Hydrus^® Microstent System (August 2018) and the iStent inject^® (June 2018). The CyPass Micro-Stent System was recalled in September 2018 for safety reasons. The iStent^® is a small (1 mm x 0.5 mm) L-shaped titanium device that is inserted into Schlemm’s canal to augment the natural outflow system. The XEN45^® is a 6 mm long porcine-derived gelatin stent inserted into the subconjunctival space bypassing the natural outflow system. The iStent inject^® system comprises 2 heparin-coated titanium stents (each having 0.23 mm diameter x 0.36 mm height, 0.08 mm central lumen diameter, and 4 0.05 mm side outlets to allow for multidirectional outflow), both inserted into Schlemm’s canal using a pre-loaded auto-injection trocar. Hydrus^® is a 8 mm nitinol, crescent-shaped microstent with alternating spines for support and windows to provide outflow, also placed into Schlemm’s canal.

The iStent^®, iStent inject^®, and Hydrus^® are FDA approved for use in combination with cataract surgery to reduce IOP in adults with mild or moderate open angle glaucoma (OAG) and a cataract that are currently being treated with medication to reduce IOP. XEN45^® was granted FDA clearance for the management of refractory glaucoma, including cases where previous surgical treatment has failed, cases of POAG and pseudoexfoliative or pigmentary glaucoma with open angles that are unresponsive to maximum tolerated medical therapy. The pivotal trial data for each, constituting the main evidentiary support, is summarized in the table below.

Pivotal Trials for FDA Approved Micro-Invasive Glaucoma Surgery*

*all results are depicted in the format (study group/control group)

According to the 2015 American Academy of Ophthalmology (AAO) POAG Preferred Practice Pattern (PPP), the “potential benefits of a combined procedure (cataract extraction with intraocular lens (IOL) implantation and glaucoma surgery) are protection against the IOP rise that may complicate cataract surgery alone, the possibility of achieving long-term glaucoma control with a single operation and elimination of the risk of bleb failure with subsequent cataract surgery when glaucoma surgery is performed first. Therefore, an ophthalmologist may reasonably choose to perform a combined surgery because of these perceived advantages to an individual patient.”¹

Indications and Limitations of Coverage

The Hydrus^® Microstent is indicated for use in conjunction with cataract surgery for the reduction of IOP in adult patients with mild to moderate POAG. In summary, this A/B Medicare Administrative Contractor (MAC) considers 1 iStent^®, iStent inject^® (device capable of delivering 2 individual iStent^®s per eye) medically reasonable and necessary for the treatment of adults with mild or moderate OAG and a cataract when the individual is currently being treated with an ocular hypotensive medication and the procedure is being performed in conjunction with cataract surgery. In that setting these procedures offer a reduction in IOP, decreased dependence on glaucoma medications and an excellent safety profile. However, their role within the glaucoma treatment algorithm continues to be clarified and differs from the role of more invasive, external filtration glaucoma surgeries such as trabeculectomy or external aqueous drainage implants. Therefore, all other indications are considered not reasonable and necessary at this time. There is no additional payment for multiple stents (so-called “dosing"), regardless of method, since a statistical benefit has not been demonstrated⁷, especially in conjunction with cataract surgery.

The XEN45^® device received 510K clearance based on having a similar mechanism (subconjunctival pathway) as “gold standard” filtration procedures (trabeculectomy and tube shunts), demonstrating “substantial equivalence” in the pivotal prospective study of patients with refractory glaucoma.⁹ Equivalency was further established by a relatively large retrospective cohort study comparing XEN45^® with trabeculectomy, finding “no detectable difference in risk of failure and safety profiles”.⁸ In addition, the American Glaucoma Society (AGS), the New York State Ophthalmological Society (NYSOS), and numerous glaucoma experts wrote to support XEN45^® as a minimally invasive method that, “would improve the access of older patients with refractory glaucoma to surgical care with reduction in post-operative discomfort, shorter post-operative disability, equivalent efficacy and safety.”

This A/B MAC considers 1 XEN45^® device per eye medically reasonable and necessary for the management of refractory glaucoma, defined (based on the pivotal trial criteria) as prior failure of filtering/cilioablative procedure and/or uncontrolled IOP (progressive damage and mean diurnal medicated IOP ≥20 mm Hg) on maximally tolerated medical therapy (i.e., ≥4 classes of topical IOP-lowering medications, or fewer in the case of tolerability or efficacy issues). XEN45^® insertion must be performed by an ophthalmologist with experience with trabeculectomy and bleb management.

Review of Relevant Literature

Technology Assessments:

American Academy of Ophthalmology (AAO): The American Academy of Ophthalmology (AAO) (Minckler, et al., 2008) conducted a technology assessment on aqueous shunts for the treatment of Glaucoma. Following a systematic review of the literature, AAO made the following conclusions: 

• Aqueous shunts are comparable to trabeculectomy for IOP control and duration of benefit.

• Larger explant surface area is related to better IOP control.

• Although primary indication for aqueous shunts is when prior medical or surgical therapy has failed, they may be used as primary surgical therapy for selected conditions such as trauma, chemical burns or pemphigoid.

• There is sufficient level I evidence that demonstrates no benefit in using antifibrotic agents as adjuncts to aqueous shunt procedures.

• There is sufficient level I evidence that demonstrates no benefit of systemic corticosteroids as adjuncts to aqueous shunt procedures.

• There are insufficient published data to draw any definitive conclusions about the relative likelihood of early postoperative hypotony with implantation of valved or nonvalved devices. 

The assessment concluded that "based on level I evidence, aqueous shunts offer a valuable alternative to standard filtering surgery or to cyclodestructive therapy for many refractory glaucomas. The failure rate is approximately the same rate for trabeculectomy with adjunctive antifibrotic agents and in favorable cases shunts may continue to function to control IOP for more than 2 decades.” 

In a prospective randomized controlled multi-center (29 sites) clinical trial, Craven et al. (2012) evaluated the long-term safety and effectiveness of a single trabecular micro-bypass stent with concomitant cataract surgery versus cataract surgery alone for mild-to-moderate OAG. Eyes with mild-to-moderate glaucoma with an unmedicated IOP of 22 mmHg or higher and 36 mmHg or lower were randomly assigned to have cataract surgery with iStent^® trabecular micro-bypass stent implantation (stent group) or cataract surgery alone (control group).  Patients were followed for 24 months postoperatively.  The incidence of adverse events was low in both groups through 24 months of follow-up. At 24 months, the proportion of patients with an IOP of 21 mmHg or lower without ocular hypotensive medications was significantly higher in the stent group than in the control group (p = 0.036).  Overall, the mean IOP was stable between 12 months and 24 months (17.0 mm Hg ± 2.8 [SD] and 17.1 ± 2.9 mm Hg, respectively) in the stent group but increased (17.0 ± 3.1 mm Hg to 17.8 ± 3.3 mm Hg, respectively) in the control group.  Ocular hypotensive medication was statistically significantly lower in the stent group at 12 months; it was also lower at 24 months although the difference was no longer statistically significant.  The authors concluded that patients with combined single trabecular micro-bypass stent and cataract surgery had significantly better IOP control on no medication through 24 months than patients having cataract surgery alone.  Both groups had a similar favorable long-term safety profile.

On June 25, 2012, the FDA approved the iStent^® Trabecular Micro-Bypass Stent System, Model GTS100R/L.  This is the first device approved for use in combination with cataract surgery to reduce IOP in adult patients with mild or moderate OAG and a cataract who are currently being treated with medication to reduce IOP. The safety and effectiveness of the iStent^® Trabecular Micro-Bypass Stent has not been established as an alternative to the primary treatment of glaucoma with medications. The effectiveness of this device has been demonstrated only in patients with mild to moderate OAG who are currently treated with ocular hypotensive medication and who are undergoing concurrent cataract surgery for visually significant cataract. 

In a retrospective, cohort study, Jea and colleagues (2012) compared the effect of ab interno trabeculectomy with trabeculectomy.  A total of 115 patients who underwent ab interno trabeculectomy (study group) were compared with 102 patients who underwent trabeculectomy with intra-operative mitomycin as an initial surgical procedure (trabeculectomy group).  Inclusion criteria were OAG, aged greater than or equal to 40 years and uncontrolled on maximally tolerated medical therapy.  Exclusion criterion was concurrent surgery.  Clinical variables were collected from patient medical records.  Main outcome measures included IOP and Cox proportional hazard ratio (HR) and Kaplan-Meier survival analyses with failure defined as IOP greater than 21 mmHg or less than 20 % reduction below baseline on 2 consecutive follow-up visits after 1 month; IOP less than or equal to 5 mmHg on 2 consecutive follow-up visits after 1 month; additional glaucoma surgery or loss of light perception vision.  Secondary outcome measures included number of glaucoma medications and occurrence of complications.  Mean follow-up was 27.3 and 25.5 months for the study and trabeculectomy groups, respectively.  Intra-ocular pressure decreased from 28.1 +/- 8.6 mmHg at baseline to 15.9 +/- 4.5 mmHg (43.5 % reduction) at month 24 in the study group and from 26.3 +/- 10.9 mmHg at baseline to 10.2 +/- 4.1 mmHg (61.3 % reduction) at month 24 in the trabeculectomy group.  The success rates at 2 years were 22.4 % and 76.1 % in the study and trabeculectomy groups, respectively (p < 0.001).  Younger age (p = 0.037; adjusted HR, 0.98 per year; 95 % CI: 0.97 to 0.99) and lower baseline IOP (p = 0.016; adjusted HR, 0.96 per 1 mmHg; 95 % CI: 0.92 to 0.99) were significant risk factors for failure in the multi-variate analysis of the study group. With the exception of hyphema, the occurrence of postoperative complications was more frequent in the trabeculectomy group (p < 0.001).  More additional glaucoma procedures were performed after ab interno trabeculectomy (43.5 %) than after trabeculectomy (10.8 %, p < 0.001). The authors concluded that ab interno trabeculectomy has a lower success rate than trabeculectomy.

In 2016, the XEN^® Glaucoma Treatment System (Allergan, Inc. Aliso Viejo, CA) was FDA 510(k) approved as a Class II aqueous shunt indicated “for the management of refractory glaucomas, including cases where previous surgical treatment has failed, cases of primary open angle glaucoma, and pseudoexfoliative or pigmentary glaucoma with open angles that are unresponsive to maximum tolerated medical therapy”.

The XEN^® Glaucoma Treatment System consists of the XEN^®45 Gel Stent preloaded into the XEN^® Injector. The XEN^®45 Gel Stent is composed of a gelatin derived from porcine dermis, formed into a tube, and then cross-linked with glutaraldehyde. 

Ab Interno Gel Stent (i.e., XEN^® Glaucoma Treatment System): Clinical trials evaluating the safety and effectiveness of the XEN^® system with phacoemulsification are lacking. Studies have primarily been in the form of case series with small patient populations (n=30) with short-term follow-ups (12 months) (Pérez-Torregrosa, et al., 2016).

After receiving FDA approval in July 2016 based on the 2-year safety and efficacy results of the COMPASS study, Alcon announced a voluntary worldwide market withdrawal of the CyPass Micro-Stent^® on August 29, 2018, after 5-year postoperative data from the COMPASS-XT safety study indicated a statistically significant corneal endothelial cell loss associated with this device.

Several additional devices are under development/investigation but have not yet received FDA approval.

Glaucoma is a disease of the eye associated with increased IOP. The majority (about 90%) of patients with glaucoma have POAG, a chronic condition in which the IOP is elevated beyond a level compatible with the continued health and function of the eye, with a gonioscopically open angle and a decreased facility of outflow.

Traditionally, POAG has been treated with topical ophthalmic medications which include timolol (a non-specific beta blocker) and latanoprost (a prostaglandin F2a agonist).  Brimonidine (an alpha agonist) and dorzolamide (a topical carbonic anhydrase inhibitor) have been employed as second line drugs when there is suboptimal control of IOP with first line agents. Third-line drugs may include apraclonidine (an alpha agonist), pilocarpine (a cholinergic agonist), acetazolamide (an oral carbonic anhydrase inhibitor) and epinephrine (a non-specific adrenergic agonist). In some patients, the treatment of POAG may involve multiple topical medications administered at frequent intervals during the day which is a significant factor in overall medication compliance.

When medications regimens fail to produce a reduction in IOP to a level significant enough to slow or arrest the progression of optic nerve damage, surgical interventions may be employed as a next step in the management of IOP. These interventions include laser trabeculoplasty and/or filtering procedures such as (a) full-thickness fistulas (e.g., thermal sclerostomy), (b) partial-thickness fistulas (e.g., trabeculectomy), (3) tubes and setons (e.g., Molteno implant, Krupin-Denver valve implant, or Ahmed glaucoma implant) and (4) cyclodestructive procedures (e.g., cyclophotocoagulation or cyclocryotherapy).

Due to complications with established surgical approaches such as trabeculectomy, a variety of devices, including aqueous shunts are being evaluated as alternative surgical treatments for patients with inadequately controlled glaucoma. 

A number of devices known as micro-stents have received FDA approval for minimally invasive glaucoma procedures. While these devices differ in their material composition and site of insertion for accomplishing enhanced drainage of aqueous humor, randomized clinical trials, cost effectiveness and quality of life studies have shown that these devices may offer a reduction in IOP, decreased dependence on glaucoma medications and an excellent safety profile.

However, stents and tensioning devices are only able to reduce IOP to the mid-teens and may be inadequate when very low IOP is needed to reduce glaucoma damage. Evaluation of outcomes of the use of micro-stents in patients with mild to moderate OAG currently treated with ocular hypotensive medication is ongoing.

Documentation Requirements

The patient's medical record must contain documentation that fully supports the medical necessity for services included within this Local Coverage Determination (LCD), See Indications and Limitations of Coverage.  This documentation includes, but is not limited to, relevant medical history, physical examination, and results of pertinent diagnostic tests or procedures. The medical record and/or test results documenting medical necessity should be maintained and made available on request.

iStent^®, iStent inject^®, and Hydrus^® must be performed in conjunction with cataract surgery on the same date of service and documented in the medical record.

The Xen^® device is FDA approved for both standalone insertion or insertion in conjunction with cataract surgery.

1. American Academy of Ophthalmology (AAO), Glaucoma Panel. Preferred Practice Pattern. San Francisco, CA: AAO; 2015. Available at: Primary Open-Angle Glaucoma Accessed 5/16/22.

2. Craven ER, Katz LJ, Wells JM, Giamporcaro JE. iStent Study Group. Cataract surgery with trabecular micro-bypass stent implantation in patients with mild-to-moderate open-angle glaucoma and cataract: Two-year follow-up. J Cataract Refract Surg. 2012;38(8):1339-45.

3. Samuelson TW, Katz LJ, Wells JM, Duh YJ, Giamporcaro JE. US iStent Study Group. Randomized evaluation of the trabecular micro-bypass stent with phacoemulsification in patients with glaucoma and cataract. Ophthalmology. 2011;118(3):459-67.

4. Stalmans I, Vera, V. Evaluation of the XEN Implant in Patients With Moderate Primary Open-Angle Glaucoma: 1-Year Results. Abstract presented at the European Glaucoma Society 2016 Congress (EGS), June 19-22, 2016, Prague, Czech Republic.

5. Samuelson TW, Chang DF, Marquis R, et al. A Schlemm canal microstent for intraocular pressure reduction in primary open-angle glaucoma and cataract: The HORIZON Study. Ophthalmology. 2019;126:29-37.

6. Samuelson TW, Sarkisian Jr. SR, Lubeck DM, et al. for the iStent inject Study Group, Prospective, randomized, controlled pivotal trial of an ab interno implanted trabecular micro-bypass in primary open-angle glaucoma and cataract: Two-year results, Ophthalmology. 2019;126(6):811-821.

7. Katz LJ, Erb C, Carceller Guillamet A, et al. Long-term titrated IOP control with one, two, or three trabecular micro-bypass stents in open-angle glaucoma subjects on topical hypotensive medication: 42-month outcomes. Clin Ophthalmol. 2018;12:255-262.

8. Schlenker MB, Gulamhusein H, Conrad-Hengerer I, et al. Efficacy, safety, and risk factors for failure of standalone ab interno gelatin microstent implantation versus standalone trabeculectomy. Ophthalmology. 2017;124(11):1579-1588.

9. Grover DS, Flynn WJ, Bashford KP, et al. Performance and safety of a new ab interno gelatin stent in refractory glaucoma at 12 Months. Am J Ophthalmol. 2017;183:25-36.

Other Contractor's LCDs:

Anthem policy SURG.00103. Intraocular Anterior Segment Aqueous Drainage Devices (without extraocular reservoir). 

UnitedHealthcare policy 2017T0443T. Glaucoma Surgical Treatments. 

BCBSMA policy 223. Aqueous Shunts and Stents for Glaucoma.

Aetna policy 0484. Glaucoma Surgery. 

BCBS policy A.9.03.21. Aqueous Shunts and Stents for Glaucoma.

• MIGS