Micro-Invasive Glaucoma Surgery (MIGS)

Language quoted from Centers for Medicare and Medicaid Services (CMS), National Coverage Determinations (NCDs) and coverage provisions in interpretive manuals is italicized throughout the policy. NCDs and coverage provisions in interpretive manuals are not subject to the LCD Review Process (42 CFR 405.860[b] and 42 CFR 426 [Subpart D]). In addition, an administrative law judge may not review an NCD. See Section 1869(f)(1)(A)(i) of the Social Security Act.

Unless otherwise specified, italicized text represents quotation from one or more of the following CMS sources:

Title XVIII of the Social Security Act (SSA):

Section 1862(a)(1)(A) excludes expenses incurred for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

Section 1862(a)(1)(D) refers to limitations on items or devices that are investigational or experimental.

Section 1833(e) prohibits Medicare payment for any claim which lacks the necessary information to process the claim.

CMS Publications:

CMS Publication 100-02, Medicare Benefit Policy Manual, Chapter 14,

10 Coverage of Medical Devices

CMS Publication 100-04, Medicare Claims Processing Manual, Chapter 23,

30 Services paid under the Medicare Physicians Fee Schedule

CMS Publication 100-08, Medicare Program Integrity Manual, Chapter 13,

5.1 Reasonable and necessary provisions in LCDs

7.1 Evidence supporting LCDs.

This LCD addresses a group of new surgical procedures for glaucoma referred to as micro-invasive glaucoma surgery (MIGS).

A.CGS considers one iStent, iStent inject, iStent inject W, or Hydrus device per eye medically reasonable and necessary for the treatment of adults with mild or moderate open-angle glaucoma (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.

B. One XEN45 or iStent Infinite device per eye is covered for the management of refractory glaucoma, defined as prior failure of a filtering/cilioablative procedure AND/OR uncontrolled intraocular pressure (IOP) defined a progressive damage and mean diurnal medicated IOP ≥20 mmHg 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.

C. The following are considered investigational in patients over the age of 18 for glaucoma management:

1. Gonitomy or ab interno trabecular bypass surgery (eg. Trabectone, Kahook Dual Blade)
2. Excimer laser trabeculostomy (i.e., ExTra ELT)
3. Viscocanaloplasty
4. Canaloplasty in combination with trabeculotomy ab interno (e.g.,OMNI® Surgical System)
5. Gonioscopy-assisted transluminal trabeculotomy (GATT)
6. Ab Interno Canaloplasty (ABiC)
7. Transculiary Fistulization
8. Cytophtocoagulation

A Contractor Advisory Committee Meeting on Micro-Invasive Glaucoma Surgery was held on 1/5/2023 hosted by Palmetto, CGS, NGS, Noridian, and WPS. Transcripts are available at: Jurisdiction J Part A - Multi-Jurisdictional Micro-Invasive Glaucoma Surgery Contractor Advisory Committee Meeting: January 5, 2023 (palmettogba.com). The input from subject matter experts will be referenced through this policy.

Primary open-angle glaucoma (POAG) affects approximately 53 million people in the world with a prevalence of 3% in the population aged 40-80 years.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. In the primary (conventional) outflow pathway from the eye, aqueous humor passes through the trabecular meshwork (TM), enters a space lined with endothelial cells (Schlemm 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 canal can disrupt the balance of aqueous humor inflow and outflow, resulting in an increase in IOP and glaucoma risk. The etiology is not fully understood but there is an association 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 measurement.¹

The Ocular Hypertension Study was a randomized controlled trial with 1636 participants from 22 clinical centers with no evidence of glaucoma between the ages of 40 to 80 years old and IOP between 24 and 32 mmHg in one eye and between 21 to 32 mmHg in the other eye. Subjects were randomized to either observation or treatment with commercially available topical ocular hypotensive medications. A comprehensive eye evaluation was conducted every 6 months for 72 months. Mean ±SD reduction in IOP in the medication group was 22.5%±9.9%. The IOP declined by 4.0%±11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P< 0.0001).2 As the only known modifiable risk factor treatment of elevated IOP to reduce risk of progression to glaucoma is considered standard of care with goal of reduction or slowing the progression of vision loss. Elevated IOP has since been the main standard to which glaucoma treatment measures. The long-standing risk of glaucoma progressive vision loss is the most significant outcome but challenging to use as primary outcome in studies. The SMEs emphasized the benefits of early reduction in IOP through medication or MIGS procedures to reduce or delay vision loss associated with glaucoma. They explained that reduction in IOP is currently the only intervention and is therefore the only marker in studies to date. While the outcome of progression of glaucoma is the final endpoint given the benefits of lowering IOP as reported in this study they do not feel a control group without intervention is appropriate.

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. AAO Guidelines recommend medical management as first line therapy and surgical intervention initially only in patients with severe visual field loss at baseline or a second-line approach for those patients with advanced open-angle glaucoma.³

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 superiorly. Aqueous drainage implants use silicone/plastic tubing and large plates to shunt aqueous to the subconjunctival space in the equatorial region of the eyeball. Complications from surgery can include cataract formation, scarring, and potentially vision-threatening complications such as over-filtration, hypotony, and infection.⁴ The five-year cataract rate was greater in those treated with surgery (19%) than medication 6.5%.5 AAO recommends laser trabeculotomy for initial and adjuvant treatment of glaucoma which is supported by evidence from >25 RCTs that demonstrate safety and successful decrease in IOP lasting for up to 3 years.³ UpToDate states for most patients pharmacological or laser therapy is first-line treatment for OAG, to avoid increased risk of complications from surgical therapy.4 Novel or emerging surgical techniques for the treatment of OAG show some promise as an alternative treatment to reduce IOP for OAG however it is not yet possible to conclude whether these novel procedures are superior, equal to or inferior to surgery such as trabeculectomy.⁶

Canaloplasty is a non-penetrating surgery performed with a microcatheter in which the Schlemm canal is expanded circumferentially by injecting a small amount of high weight molecular viscoelastic agent through the catheter followed by placement of a permanent suture under tension in Schlemm’s canal to create an intrascleral reservoir.^7,8 A systematic review and meta-analysis compared canaloplasty with trabeculectomy. The analysis included 28 studies with two RCTs, 11 prospective reviews and 18 retrospective reviews for 1498 subjects. The authors found that the reduction in IOP was significantly higher after trabeculotomy with an average difference of 3.61 (95% CI 1.69 to 5.53) compared to a reduction of 2.11 (95% CI 1.80 to 2.42) in one year. Canaloplasty was associated with a lower incidence of complications than trabeculotomy.8 Limitations included the inclusion of retrospective studies without control groups resulting in high heterogeneity and risk of publication bias. There was no conflict of interest reported. Another meta-analysis included eight retrospective or prospective cohort studies. This report drew similar conclusions with a greater reduction in IOP from trabeculectomy as compared to canaloplasty with reduction in complications in the canaloplasty group at 12 months. This report was limited by the lack of randomized controlled trials and high heterogeneity especially at 12 months.⁹

Goniotomy is surgery in which an incision or excision of trabecular meshwork with a blade or other surgical instrument for at least three (3) clock hours to create an opening into the Schlemm canal from the anterior chamber, via an internal approach through the anterior chamber.¹⁰ Goniotomy was first described by Barkan as the incision of one quarter to one-third of the nasal trabecular meshwork (TM) via a temporal peripheral corneal incision under intraoperative gonioscopy in a series of 11 adult eyes in 1936.¹¹ Traditional goniotomy is the procedure of choice for congenital glaucoma and needs simple and inexpensive equipment.¹² Until recently, goniotomy was viewed as a surgical approach reserved for the treatment of trabeculodysgenesis associated with congenital glaucoma. As minimally invasive glaucoma surgical options have burgeoned goniotomy for adult eyes with glaucoma has resurfaced. There is a paucity of literature on the role of goniotomy in adult glaucoma and in the absence of trabecular dysgenesis.¹³ In adults, there have been mixed long-term results with these procedures likely due to incomplete removal of the trabecular meshwork and inflammation from damage to surrounding structures.

Micro-invasive or Minimally Invasive Glaucoma Surgeries (MIGS)

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. Ab-interno disruption and ablation of the TM increases outflow at the level of the juxtacanalicular TM and the inner wall of Schlemm’s canal (SC).¹⁴ 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 fewer severe complications.
It is this potential to 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. MIGS fall into two main categories: aqueous stent procedures and ab interno surgical procedures.

Minimally Invasive Stent Procedures

Aqueous shunts emerged and there was hope these could replace trabeculectomy to bypass these complications. However approximately 10% of devices fail annually and shunts still have other complications, including corneal endothelial failure and erosion of the overlying conjunctiva.¹⁴ A 2017 Cochrane meta-analysis included three randomized control trials (n=380) and reported that IOP was not different in patients who underwent aqueous shunt compared with trabeculectomy (mean difference 2.55 mmHg, 95% CI -0.78 to 5.87).8 The authors conclude that methodology and data quality among existing randomized controlled trials of aqueous shunts was heterogeneous across studies, and there are no well-justified or widely accepted generalizations about the superiority of one surgical procedure or device over another. In addition to the paucity of high-quality literature, MIGS procedures have not been commercially available long-term contributing to the lack of long-term data.

FDA approved/cleared micro-invasive surgical stents available at the time of this LCD revision includes the iStent Trabecular Micro-Bypass Stent (Month, 2011), the CyPass Micro-Stent System (July, 2016), the XEN Glaucoma Treatment System (November, 2016), the Hydrus Microstent (August, 2018), the iStent inject (June, 2018), iStent inject W (July, 2020), iStent Infinite (August, 2022). 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 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 four 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 an 8 mm nitinol, crescent-shaped microstent with alternating spines for support and windows to provide outflow, also placed into Schlemm’s canal. The iStent inject W Trabecular Micro-Bypass System Model G2-W stents include a wider proximal end in the anterior chamber of 360 µm, rather than 230 µm for Model G2-M-IS. The iStent infinite is a sterile, single-use injector system preloaded with three micro-scale wide-flange stents (each having 0.36 mm diameter x 0.36 mm height, 0.08 mm central inlet and outlet lumen diameter, and 4 0.05 mm side outlets to allow for multidirectional outflow), inserted into Schlemm’s canal. CyPass is a 6.35 mm long fenestrated microstent made of biocompatible polyimide inserted into the supraciliary space, thus using an alternative outflow system. The XEN45 is a 6 mm long porcine-derived gelatin stent inserted into the subconjunctival space, bypassing the natural outflow system.

iStent, iStent inject, iStent inject W. Hydrus and CyPass were FDA approved (Cypass recalled by FDA for safety concerns September 2018) for use in combination with cataract surgery to reduce IOP in adults with mild or moderate OAG and a cataract that are currently being treated with medication to reduce IOP. The iStent infinite® is indicated for use in adult patients with primary open-angle glaucoma (POAG) in whom previous medical and surgical treatment has failed. XEN45 was granted FDA clearance for the management of refractory glaucoma, 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 published pivotal trial data for each, constituting the main evidentiary support, is summarized in the attached table.^15-19 MIGS Pivotal Trials

A 2020 Cochrane review on ab interno trabecular bypass surgery with Hydrus microstent for OAG reported on 3 studies (all sponsored by manufacturer Iventis Inc. who makes the Hydrus stent) with 808 patients from USA and other countries with mild-moderate OAG who had Hydrus stent placement at the time of cataract surgery reduced unmedicated IOP (after washout) by 2 mmHg more compared to cataract surgery alone (mean difference (MD) -2.00, 95% CI -2.69 to -1.31; 2 studies, 619 participants; I2=0%; moderate-certainty evidence). Their review concludes with moderate-certainty evidence that the Hydrus microstent with cataract surgery compared to cataract surgery alone can decrease IOP lowering medication.²⁰ Ahmed et al reported on 152 eyes with OAG were randomized to MIGS with Hydros Microstent or 2 iStents and followed for 12 months. At 12 months, the Hydrus had a greater rate of complete surgical success (P < 0.001) and reduced medication use (difference -0.6 medications, P=0.004). More Hydrus subjects were medication free at 12 months (difference 22.6% P=0.0057) leading to study conclusion that Hydrus related to higher surgical success rates than iStent.²¹

A 2021 Cochrane Systematic Review and Network Meta-analysis explores the outcomes from 6 to 60 months of minimally invasive glaucoma surgery. The report concluded that in comparison with cataract surgery alone, the addition of trabecular bypass surgery (Hydrus or iStent) safely improved glaucoma control without use of medication and the Hydrus also conferred approximately 2.0 mmHg IOP lowering (95% CI, −2.7 to −1.3 mmHg; estimate based on 2 trials). Available data was insufficient to compare other minimally invasive glaucoma surgery techniques.22 AAO rated this as moderate quality, strong recommendation.¹ Very low-certainty evidence suggested that adding iStent to cataract extraction lowered IOP an additional 5.0 mmHg (95% CI, −7.5 to −2.5 mmHg; estimate based on 3 trials) at short-term follow-up, but this outcome was not statistically significant at medium-term follow-up and was rated as insufficient quality evidence by AAO with recommendation to leave to the discretion of the treating ophthalmologist.¹

A prospective randomized study reported on 119 subjects over a 42-month time period with APOG, IOP 18-30 mmHg in subjects with uncontrolled, mild/moderate glaucoma using 1-3 glaucoma medications or range of IOP from 22-38 mmHg without medication were randomized to one (n=38), two (n=41), or three (n=40) iStent trabecular micro-bypass stents in a standalone procedure. Preoperative mean medicated IOP was 19.8±1.3 mmHg on 1.71 medications in one-stent eyes, 20.1±1.6 mmHg on 1.76 medications in two-stent eyes, and 20.4±1.8 mmHg on 1.53 medications in three-stent eyes. At 42-months medicated IOP was 15.0±2.8, 15.7±1.0 and 14.8±1.3 mmHg in the three groups and IOP reduction ≥20% without medication was achieved in 89%, 90%, and 92% of one-, two-, and three-stent eyes, respectively, at Month 12; and in 61%, 91%, and 91% of eyes, respectively, at Month 42. The authors conclude that multiple iStent® device(s) produced safe, clinically meaningful IOP and medication reductions through 42 months postoperatively and there was greater and more sustained reduction with multiple stents.²³ Limitations include lack of blinding, missing data points (baseline and post-operative IOP measurements), lack of standardized cataract grading system or threshold for completion of cataract surgery, potential confounding, and risk of bias.

Ab Interno Trabeculectomy

Trabeculotomy ab interno (also called goniotomy) is defined as a procedure in which the trabecular meshwork is opened for at least 3 contiguous clock hours or when multiple incisions are performed opening the trabecular meshwork over an area of at least 90 degrees at the level of the juxtacanalicular TM and the inner wall of Schlemm’s canal (SC).^10,14 There has been a shift in practice to the use of tube-shunt procedures and a decrease in the use of trabeculectomy over the past decade.^24,25 There has been the emergence of multiple new devices and procedures for the excision or cleavage, dilation, or stenting of various extents of the trabecular meshwork and the inner wall of Schlemm’s canal under gonioscopic guidance. The IOP-lowering effect of the trabecular MIGS is limited by resistance in the distal outflow pathways and the episcleral venous pressure with a mean in mid-teens.¹ The subject matter experts state that clinical experience and glaucoma fellowship guide their decision in terms of patient selection but acknowledge a lack of standards in terms of patient selection for procedures beyond stents. It was stated that laser trabeculoplasty is the least invasive and often first line option for open angle glaucoma with progressive invasiveness with devices such as Trabectome, Excimer laser and KDB as methods of goniotomies.¹

The Trabectome™(NeoMedix, Tustin, CA, USA) is a device consisting of a handpiece, footplates, and electrocautery electrodes. The footplate enters Shlemm’s canal and energy is applied from the electrode disrupting the TM, and interrogating the tissues, and exposing the canal to the anterior chamber.²⁶ The use of the instrument was initially reported in a prospective trial of 101 patients with open angle glaucoma with a mean preoperative IOP of 27.6 ± 7.2 mmHg. They were followed for 30 months where the mean IOP was 16.3 ± 3.3 mmHg (n=11). The mean percentage drop over the course of follow-up was 40% and the decrease was statistically significantly less at all postoperative measurements from the preoperative level. They reported overall success defined as IOP ≤ 21 mmHg with or without medications and no subsequent surgery was 84%. One hundred percent of patients experienced interoperative reflux bleeding, but complications were minimal and not vision threatening. The authors concluded that Trabectome offers a minimally invasive and effective approach to glaucoma treatment which spares conjunctiva and does not preclude subsequent standard filtering procedures.²⁷ Limitations include a lack of a control group and randomization, and risk of bias.

A 2021 Cochrane Review of randomized controlled trials to evaluate safety and efficacy of ab interno trabecular bypass surgery with Trabectome for open angle glaucoma at two-year follow-ups identified 10/19 subjects in the intervention group concluding low certainty evidence. The authors conclude there is no high-quality evidence for the outcome of ab interno trabecular bypass surgery with Trabectome for open angle glaucoma calling for the need for properly designed randomized controlled trials.²⁸

A prospective interventional case series of 304 consecutive eyes with glaucoma undergoing cataract surgery received trabeculectomy with Trabectome. The mean IOP was 20.0 mmHg 6.3 (SD) preoperatively, 14.8 ± 3.5 mmHg at 6 months, and 15.5 ±2.9 mmHg in 1 year. Use of glaucoma medication was reduced at 1 year. Nine patients underwent subsequent glaucoma procedures. 78.4% of the patients had blood reflux which resolved within a few days. The authors support the use of trabeculectomy by the internal approach using the Trabectome at the time of cataract surgery for lowering IOP.29 Limitations to the study include the lack of control group or randomization, high-risk of bias and lack of long-term follow-up.

A retrospective interventional single surgeon, single center case series reported on 246 patients undergoing ab interno trabeculotomy with Trabectome was reported. Eighty-eight cases were ab interno trabeculotomy alone and 158 were in combination with cataract surgery. The mean preoperative IOP was 21.6 ± 8.6 mmHg and at 24 months post operatively the mean IOP was reduced by 29% to 15.3 ± 4.6 mmHg (p=0.001) with a reduction in the number of glaucoma medications needed. The authors divided the patients into Criteria A requiring a postoperative of IOP ≤ 21 mmHg or ≥ 20% reduction from preoperative IOP and Criteria B requiring IOP of ≤ 18 mmHg and ≥ 20% reduction in IOP. Success rate was 62% (95% CI, 56%–68%) using Criteria A and 22% (95% CI, 16%–29%) using Criteria B. Using a more stringent criteria for success the overall success rate of ab interno trabeculotomy can drop within 24 months after surgery to levels that may be clinically unacceptable. The authors conclude that the surgery was most appropriate for patients requiring a target IOP of 21 mmHg or above.³⁰ The study is limited by the retrospective design with lack of control group or randomization and strengthened by large sample size, longer term follow-up than other studies and while it was funded by outside sources, they did not have a role in the design or conduct of the research or reporting of results.

Benefits to this approach are that it is conjunctiva sparing therefore does not preclude future bleb-associated surgeries and the reported studies show low complication rates. However, complications can occur with symptomatic delayed onset hyphema between 2 to 31 months after the procedure in the absence of further surgeries of trauma reported. Additionally transient increase in IOP has been reported and vision threatening IOP increase requiring urgent surgery was also reported.³⁰

Trabectome-mediated ab-interno trabeculectomy states an average the IOP was reduced by 36% to a final mean IOP of 16 mmHg in a meta-analysis.³¹ The meta-analysis included fourteen papers, but was fraught with significant heterogeneity, combining prospective, cohort, and retrospective studies and case series, lack of clear definition for glaucoma, variable outcome and duration of follow-up questioning the reliability of this conclusion.

One subject matter expert stated there were at least nine studies in support of Trabectome. These were retrospective and prospective but resulted in decrease in IOP, and while there are no randomized controlled trials, they felt that there is data to support the procedure.

The Goniotome + I/A (Irrigation and Aspiration), while like the Trabectome, does not require a high frequency generator or peristaltic pump end utilizes V shaped, serrated sharp blades made with femtosecond laser to induce a dual cut along the anterior and posterior TM and is available with active aspiration and irrigation. Results are like the Trabectome.¹⁴
The Kahook Dual Blade (KDB, New World Medical, Rancho Cucamonga, CA) is a device designed for more complete removal of the TM through a minimally invasive approach. The tip of the blade is inserted through the TM, the ramp of the device gently stretches the TM and guides it towards the dual blades, which create parallel incisions, allowing excision of a strip of the TM. The developers report that this achieves near complete removal of the TM with less damage to the surrounding structures and that minimizing residual TM leaflets may reduce fibrosis and enhance outcomes.³²

The KDB Goniotomy Study Group conducted a retrospective analysis of patients who had cataract surgery plus Kahook Dual Blade excisional goniotomy or cataract surgery plus iStent trabecular micro-bypass in eyes with mild to moderate open-angle glaucoma and visually significant cataract whose IOP was controlled with one or more topical IOP-lowering medications.³³

A retrospective review on 53 eyes treated with KBD blade and followed for 6 months report reduction from 7-10.3 mmHg (29.8-43.8%; p<00001) without significant adverse events.³⁴ A retrospective study reported on 32 eyes that had KDB goniotomy alone and 165 eyes with KDB goniotomy combined with cataract surgery. Surgical success was defined as a reduction in IOP of at least 20% from baseline at 12 months and/or reduction of at least one glaucoma medication. They reported that 71.8% in the cataract plus KBD group (n=124) and 68.8% for the KBD alone group reached this measure. Long-term visual acuity was unchanged from baseline in the KCD-alone group and improved in the group that also had cataract removal. The most common complications were transient hyphema (17.3% at day 1) and IOP spike >10 mmHg from baseline at 1 week (10.2%). The authors conclude that goniotomy with the KBD knife is a safe and effective procedure at reducing IOP and medication burden as a standalone procedure or in combination with cataract removal.³² Limitations of the study include the retrospective design with lack of randomization or control, small sample size especially in the non-cataract removal group, lack of long-term follow-up, risk of bias, and mild to moderate baseline IOPs.

A retrospective analysis with data collected from eight US centers including 42 eyes of which 36 had mild to severe open angle glaucoma and the remaining having other forms of glaucoma with baseline IOP of 21.6 mmHg were included. Patients underwent excisional goniotomy with KDB as a standalone procedure. At 3, 6, and 12 months postoperatively, mean IOP reductions from baseline were 4.6 mmHg (22.3%), 5.6 mmHg (27.7%), and 3.9 mmHg (19.3%) (p≤0.001 at each time point). 14.3% (6/42) required additional glaucoma surgery during the 12 month follow-up.³⁵ Limitations include retrospective design with lack of randomization and control, small sample size, lack of long-term follow-up, inclusion of eyes without glaucoma and risk of bias.

A retrospective review of 42 eyes from 36 patients with severe glaucoma (severe-stage glaucoma, defined by ICD-10 as optic nerve abnormalities consistent with glaucoma, and glaucomatous visual field abnormalities had cataract removal with KDB goniotomy were reported. Preoperative baseline mean IOP was 17.1±4.8 mmHg (mean ± SD) and mean IOP reduction was 2.1±4.67 mmHg (p=0.022). At 6 months, 64.3% (27/42) of eyes had achieved IOP ≤ 15 mmHg without additional glaucoma procedures, 45.2% (19/42) and 45.2% (19/42) were on fewer medications and 31% (13/42) on no medications. Visually significant complications were experienced by 7.1% (3/42) of eyes, and 7.1% (3/42) required additional IOP-lowering procedures within 6 months of surgery.³⁶ Limitations of the study include retrospective design with lack of control group, small sample size, short term follow up, and risk of bias.

A retrospective comparison study involved 315 eyes of 230 adults. The KDB+ phaco group included 190 eyes, and the iStent+phaco group included 125 eyes. All were treated with at least one topical IOP-lowering medication prior to surgery. Baseline characteristics were mostly similar except baseline mean IOP (standard error) was higher in the KDB+cataract group [18.2 (0.3) mmHg] than in the iStent+ cataract group [16.7 (0.3) mmHg] (p=0.001). Exclusions included ocular co-morbidities that reduced potential post-operative best-corrected distance visual acuity, if cataract surgery was complicated by vitreous loss, vitrectomy, or lens implantation in the sulcus or the anterior chamber; or if the eye had undergone any prior incisional glaucoma surgery. The primary end point was reduction of IOP 20% from baseline or reduction of IOP-lowering medications from baseline. A single measure of IOP was obtained at day 1, week 1, month 1, month 3 and month 6. There was a change from baseline of 17.9 to 13.6 or -4.2 (p= <0.001) in the KDB group and from 16.7 to 13.9 or -2.7 (p=0.001) in the iStent group. Reduction on IOP reducing medication was achieved in both groups. The proportion of eyes achieving a postoperative reduction in the use of IOP lowering medications (a reduction of at least one med) was comparable in the two groups.³³ Limitations include retrospective design with lack of randomization or controls, baseline IOPs were different between the 2 groups, high-risk of bias, single measure of IOP, and the population with mild-moderate glaucoma with mean of 17.5 mmHg at baseline.

A prospective interventional case series reported on 32 eyes of 30 consecutive patients with early to moderate glaucoma and IOP ≥21 mmHg without medication or < 21 mmHg with medication with cataracts. Goniotomies were performed with a 25-gauge needle which was bent from its hub for better handling and connected to irrigation and advanced for at least 45 degrees in the superior and inferior direction to incise the pigmented part of the trabecular meshwork and expose the Schlemm’s canal into the anterior chamber for 90 degrees. Patients were followed at one day, one week, one month, three months and six months after surgery and two IOP measurements were taken at each visit. Mean ± SD IOP at baseline was 21.8 ± 4.6 mmHg. Mean ± SD IOP at one-day (13.8 ± 4.4 mmHg), one-week (13.4 ± 4.3 mmHg), one-month (16.9 ± 6), three-month (16.3 ± 4.5 mmHg) and six-month (14.8 ± 3.9 mmHg) visits was significantly lower than baseline (P < 0.001). There was a 25.2% and 32.1% IOP reduction at three months and six months after surgery, respectively. There was a reduction in antiglaucoma medications from baseline. There were no serious complications and minor complications were transient.¹² The authors report no conflicts of interest. Limitations of this study include a lack of control group, short term follow-up, and small sample size.

A retrospective comparative study sought to understand outcome of goniotomy in adults reported on 76 patients with moderately controlled IOP ≤ 21 mmHg using medication who underwent conventional goniotomy using keratome blade and viscoelastic material during cataract surgery and were compared to those undergoing cataract surgery alone. Baseline IOP was 18.2 ± 2.4 mmHg in the goniotomy + cataract group and 17.4 ± 1.9 mmHg in the cataract only group. The reduction in IOP from baseline in the combined goniotomy group was significantly greater at 12 months compared to the cataract alone group (−3.1 ± 2.9 mmHg vs −1.3 ± 2.4 mmHg p < 0.05). The success rate was 76.7% in the combined goniotomy group and 50.0% in the cataract only group at 12 months (p = 0.021). Medication use was reduced and there were no significant complications observed in either group.37 The authors report no disclosures and limitations include retrospective design with lack of control group, small sample size and short-term follow-up.

Excimer laser trabeculostomy (i.e., ExTra ELT)

Excimer laser trabeculotomy is a MIGS procedure that uses non thermal excimer laser to create multiple microscopic channels in the TM and wall of Schlemm’s canal. This is proposed to prevent scarring to allow fluid flow through TM to reduce IOP. The device has been used in Europe and has received Category III CPT codes in US, however it is not currently FDA approved in the United States.

Viscocanalostomy, Phacoviscocanalostomy, and Ab interno canaloplasty (ABiC)

Viscocanalostomy and Phacoviscocanalostomy involves creating a scleral reservoir and the injection of viscoelastic fluid into the ostia of the canal opening the passage from the anterior chamber into the canal to lower IOP. Unlike trabeculotomy this allows full thickness penetration into the anterior chamber of the eye. When performed at the time of cataract surgery it is called phacoviscocanalostomy. A Cochrane review included five studies with 311 eyes. The studies reviewed were randomized and quasi-randomized and compared trabeculotomy (160 eyes) to viscocanalostomy (50 eyes) for OAG and concluded based on limited evidence that trabeculotomy offered better IOP control.³⁸ A meta-analysis reviewed 10 RCT with 458 eyes and concluded trabeculotomy requires significantly less postoperative antiglaucoma medications as compared to viscocanalostomy. Trabeculectomy was associated with a significantly lower mean intraocular pressure at 6, 12 and 24 months when compared to viscocanalostomy (six months MD 2.25 mmHg, 95% CI 1.38 to 3.12; eight studies, 12 months MD 3.64 mmHg, 95% CI 2.74 to 4.54; six studies and 24 months MD 3.42 mmHg, 95% CI 1.80 to 5.03; three studies) and was consistently superior to viscocanalostomy in all subgroup analyses. The risk of complications including hypotony, hyphema, shallow anterior chamber and cataract formations were lower in the viscocanalostomy group, however the viscocanalostomy group had a significantly higher risk of perforation of Descemet membrane.³⁹ This meta-analysis was limited by methodological concerns within some of the studies, significant heterogenicity and short-term follow-up. Additional case series and retrospective reviews address phacoviscocanalostomy but the paper concludes a lack of evidence to support the procedure.

Ab interno canaloplasty (ABiC), also called viscocanaloplasty, differs from viscocanalostomy by injection of viscous medication to create the opening in Schlemm’s canal. The procedure is performed through a single corneal incision and involves a 360-degree viscodilation of the canal using a device (such as the iTrack microcatheter (Ellex) or the VISCO360® handpiece (Sight Sciences) and an ophthalmic visco-elastic device inserter. If performed with cataract surgery the same corneal incision can be used or performed as a standalone procedure. As of April 30, 2019, the VISCO360 is no longer available for commercial distribution (Access Gudid, 2020). Studies consist of retrospective reviews.
A non-randomized, retrospective, single centered paired eye study assessed the 12-month outcome of 12 patients (mean age 73.8 ±12.6 years) with POAG who underwent ABiC in one eye and canaloplasty in the other eye as either a standalone procedure or combined with cataract excision. In the canaloplasty group, the mean preoperative IOP was 18.1±3.9 mmHg on 2.4±0.5 medications, which reduced to 13.5±2.2 mmHg (p<0.05) on 0.9±0.9 medications (p<0.001). In the ABiC group, the mean preoperative IOP was 18.5±3.4 mmHg on 2.4±0.5 medications and postoperative IOP was 13.8±2.2 mmHg (p<0.05) on 0.8±0.8 medications (p<0.05). The authors conclude comparable results from the two procedures.40 This study is limited by the small sample size, risk of bias and lack of control group and randomization.

A retrospective cohort study included 36 eyes who underwent ABiC alone or in combination with cataract surgery and followed for 12 months. They report IOP decreased from 19.8 ± 4.1 to 13.8 ± 3 mmHg at 12 months follow-up (n = 21, p < 0.001) without major complications.⁴¹ Another retrospective report on 54 eyes which underwent ABiC reported a mean IOP decreased from 23.6 ± 7.4 mmHg preoperatively to 14.2 ± 2.9 mmHg (-39.8%; p <0.001) after 12 months. 35.2% (n=19) were considered surgical failures due to uncontrolled IOP and required further surgery.⁴¹ Both studies were limited by retrospective design, small sample size number, and lack of control or randomization.

A retrospective cohort of 25 eyes were followed after ABiC with or without cataract surgery and reported a reduction from baseline mean IOP of 20.24 mmHg ± 5.92 (n = 25) was reduced to 10.64 mmHg ± 2.77 (n = 25, p < 0.001), 12.55 mmHg ± 3.33 (n = 22, p < 0.001) and 13.67 mmHg ± 2.15 (n = 21, p < 0.001) at 1 day, 1 year and 2 year follow-up visit, respectively. The authors conclude this is a safe and effective option with long-term reduction in IOP, however the study was limited by retrospective design, small sample size, lack of controls and risk of bias.⁴²

A retrospective study included 54 eyes that underwent ABiC with cataract surgery and reported a mean IOP decreased from 23.6 ± 7.4 mmHg preoperatively to 14.2 ± 2.9 mmHg (-39.8%; p<0.001) after 12 months. The authors reported a reduction in the need for antiglaucoma medication and concluded that at 12 months complete success (IOP reduction ≥ 20%) in 46% of eyes and qualified success in 65% of eyes. They reported the most common post operative adverse event was IOP spikes in 22.2%. Nineteen eyes (35.2%) were considered surgical failures due to uncontrolled IOP and 36.8% required filtering surgery (n=7).43 Limitations of this study include the retrospective design, risk of bias, caucasian only population, lack of controls and variability in patient selection and follow-up.

The AAO Preferred Practice Guidelines states ABiC reduces in IOP up to 12-months, but success in reduction of postoperative glaucoma medication is not clear. AAO does state that it appears to be equivalent to ab externo canaloplasty, however this is based on the single low-quality evidence study.¹

Canaloplasty in combination with trabeculotomy ab interno and Gonioscopy-assisted transluminal trabeculotomy (GATT)

A retrospective study on 81 patients who underwent sequential canaloplasty in combination with trabeculotomy ab interno with the OMNI system (Sight Science) in conjunction with cataract surgery in mild-moderate OAG were followed for 12 months. The authors reported a reduction in IOP in those with IOP > 18 mmHg at baseline of 21.9 to 15.1 mmHg, (p < .0001) and remained controlled in those with IOP at 18 mmHg (14.1 to 13.4 mmHg, p = .3177).44 A retrospective observational study included 88 eyes from 73 patients with mild to moderate OAG with (n=30) or without (n=50) cataract surgery who underwent ab- interno SC viscodilation performed with the OMNI system. The authors reported a reduction in IOP from 23.0 to 15.6 mmHg, (p < 0.001) in those OMNI alone, and from 21.5 to 14.1, p < 0.001, in those with OMNI + cataract surgery. Complications included hyphema, mild hypotony, IOP spikes up to one-month post-surgery but without major complications and 15% required subsequent surgical procedures.⁴⁵ Additional retrospective studies with 81 patients and 48 patients report similar success at 12 months.44,46 Both studies are limited by the retrospective design with lack of randomization and control. Additional studies include case series.

A prospective, multicentered study reported 6-month outcomes for 137 patients who underwent 360° canaloplasty and 180° trabeculotomy using the OMNI® Surgical System concomitantly with phacoemulsification in patients with open-angle glaucoma (OAG). Medication washout was performed and IOP after washout was 23.8 ± 3.1 mmHg at baseline. At month 6, 78% (104/134) were medication free with IOP of 14.2 mmHg with a mean reduction of 9.0 mmHg (38%). 100% (104/104) had a ≥ 20% reduction in IOP and 86% (89/104) had IOP ≥6 and ≤18 mmHg. The study is ongoing with plans for 24-month follow-up.47 A strength of this study is the medication wash-out and limitations are lack of randomization and controls, short-term data and risk of bias.

Gonioscopy-assisted transluminal trabeculotomy (GATT) involves a circumferential 360-degree trabeculomtomy without conjunctival or scleral incisions. It is performed by making a microincision in the cornea and uses a retractable illuminated microcatheter as an alternative means of performing 180- to 360- degree ab interno trabeculotomy unroofing the entire TM.1 This can employ either a microcatheter, suture or TRAB 360 handpiece (Sight Science).

A retrospective case series introduced the procedure and reported on 85 consecutive patients with OAG who underwent GATT with at least 6 months follow-up data available. The authors reported 57 patients with primary OAG had a mean decrease in IOP by 7.7 mmHg and with secondary OAG a decrease of 17.2 mmHg. 9% of patients required further glaucoma surgery with a cumulative failure rate of one year ranging from 0.1 to 0.32.48 Limitations include retrospective design, lack of control and randomization. Another retrospective report included 32 patients who underwent GATT at the time of cataract surgery and reported a decrease in IOP from average preoperative IOP was 34.2 ± 10.6 mmHg to 11.2 ± 2.4 mmHg at 6 months.⁴⁹

A prospective, single armed trial including twenty eyes of 20 subjects with mild to severe POAG underwent incisional goniotomy and canal of Schlemm viscodilation using the STREAMLINE Surgical System (New World Medical, Rancho Cucamonga, CA) following cataract extraction after a washout of all glaucoma medication. The authors reported at six months greater than 20% reduction in IOP from baseline in 89.5% of eyes from a mean IOP of 23.5±2.5 mmHg preoperatively (unmedicated IOP) to 14.7±2.4 mmHg at the 6-month follow-up visit (p<0.001) with a 57.9% decrease in IOP lowering medication.50 Limitations of the study include lack of randomization or control groups, small sample size and risk of bias. Application of this technology outside of a setting of cataract was not explored in this study.

Glaukos iAccess Trabecular Trephine is another device for cutting of the TM, but no publications on the device were found.

Transciliary Fistulization

Transciliary fistulization, also called Singh filtration, is a minimally invasive glaucoma procedure in which a specialized laser device (e.g., Fugo Blade) is used to create a small opening in the sclera under the conjunctival flap two drain the eyes posterior chamber and reduce IOP. The Fugo Blade (MediSURG Ltd., Norristown, PAreceived 510(k) clearance for marketing from the U.S. Food and Drug Administration (FDA) for sclerostomy for the treatment of primary open-angle glaucoma where maximum tolerated medical therapy and trabeculoplasty have failed.⁵¹

This approach was introduced in 2002 in a case series of 147 patients followed for 6 months after transcilary fistulization with modified Fugo Blade (Plasma Blade) reporting successful decrease in IOP.⁵² Another case series reported on 60 eyes but lacked long-term follow-up due to high lost to follow-up (>50%).53 There are no US clinical trials, RCT or SR that address this technology. The Category III code, fistulation of sclera for glaucoma, through ciliary body, is no longer active.

Cytophotocoagulation

Ciliary photocoagulation consists of using a laser to deliver thermal energy to the pigmented tissue of the ciliary body to induce coagulation necrosis.⁵⁴ This gained in popularity in the 1930s but is limited due to complications, but modifications of the technique have reduced these complications. A Cochrane review on cyclodestructive procedures for glaucoma limited to RCT found one RCT that compared cyclophotocoagulation to other procedures. This trial included 92 eyes that underwent diode transscleral cyclophotocoagulation (TSCPC) and concluded there was not sufficient evidence to evaluate effectiveness.⁵⁵ Another concern with the procedure is the risk of scarring and the potential impact that could have on future filtrating surgeries if necessary.

IOP and Cataract Surgery

The effect of cataract surgery on IOP in patients with open-angle glaucoma has been a subject of debate. Studies have found that there is a small decrease in IOP after phacoemulsification for cataract removal in patients without glaucoma, glaucoma suspects and glaucoma patients. This modest effect seems to decrease after two years but is sustained until five years after the cataract surgery. A significant IOP reduction has been found in patients with pseudoexfoliation glaucoma (PXG). The American Academy of Ophthalmology (AAO) conducted a meta-analysis56 that concluded a 13% average decrease in IOP after phacoemulsification while other studies report ranges from -7% to -22% reductions and the range of medication usage after cataract surgery for glaucoma was widely variable.57 Overall, there seems to be a modest reduction in IOP after cataract surgery by phacoemulsification, however the results are somewhat unpredictable and not always sustainable. Patients with higher baseline IOP’s seem to have the greatest effect. However, cataract removal does not seem to be a sufficient treatment for POAG patients who have a surgical indication for IOP reduction. This has led to the frequent practice of performance of minimally invasive glaucoma surgeries (MIGS) at the time of cataract removal. Few studies have reported on the results of MIGS performed as standalone procedures.

The American Academy of Ophthalmology (AAO) published a systematic review in 2015 on the effect of phacoemulsification (cataract removal) on intraocular pressure in glaucoma patients. Thirty-two studies met inclusion criteria assigned level of evidence based on grading adopted by AAO. The studies indicated improvement in IOP for all three types of glaucoma reviewed: open-angle glaucoma (POAG; including normal-tension glaucoma), pseudoexfoliation glaucoma (PXG), or primary angle-closure glaucoma (PACG). For POAG, 9 studies (total, 461 patients; follow-up, 17 months) showed that phacoemulsification reduced IOP by 13% and glaucoma medications by 12%. For PXG, 5 studies (total, 132 patients; follow-up, 34 months) showed phacoemulsification reduced IOP by 20% and glaucoma medications by 35%. For chronic PACG, 12 studies (total, 495 patients; follow-up, 16 months) showed phacoemulsification reduced IOP by 30% and glaucoma medications by 58%. Patients with acute PACG (4 studies; total, 119 patients; follow-up, 24 months) had a 71% reduction from presenting IOP and rarely required long-term glaucoma medications when phacoemulsification was performed soon after medical reduction of IOP. Trabeculectomy was uncommon after cataract removal in this study population.⁵⁶

A 2017 systematic review and meta-analysis was conducted to evaluate 32 studies for the effect of phacoemulsification on IOP and topical medication use for glaucoma patients. A 12%, 14%, 15%, and 9% reduction in IOP from baseline occurred 6, 12, 24, and 36 months after phacoemulsification and medication use was decreased at all endpoints. The benefits of cataract removal on decreasing IOP lasted at least 36 months but gradually lost effect after the first 24 months.⁵⁸ Study is limited by high heterogeneity, few high quality RCT available, small sample sizes and risk of bias.

A 2019 retrospective analysis of 70 eyes with POAG controlled medically who underwent cataract surgery by phacoemulsification were included. One year after phacoemulsification, IOP decreased by a mean 1.15 ± 3 mmHg (6.8 ± 18.1%) (p = 0.01) and the number of glaucoma medications remained unchanged with a difference of − 0.1 ± 0.43 (p = 0.09). Higher preoperative IOP was associated with a greater IOP decrease after 1 year of follow-up (p < 0.001). A spike in IOP was common in the first week following the surgery. The study found that the drop in IOP from cataract surgery alone was modest and did not significantly impact the amount of glaucoma medication used.57 This study was limited by the retrospective design, small sample size lack of randomization and control groups.

The Horizon Study¹⁹ and an analysis from the Flight Blindness (FGB) international registry⁵⁹ which followed patients who had cataract surgery with either an eye stent or Hydrus microstent for 24 months demonstrated sustained IOP reduction with good safety profile. The SMEs stated that the placement of a stent at the time of cataract surgery and patients at risk for glaucoma due to elevated intraocular pressure has become standard of care due to the potential reduction in vision loss and blindness secondary to glaucoma.

Comparative Studies

A 2020 systematic review and meta-analysis included 77 articles including 28 comparative studies and 12 RCTs on the available MIGS procedures. The authors report weighted mean intraocular pressure reductions from all analyzed studies were: 15.3% (iStent), 29.1% (iStent inject), 36.2% (ab interno canaloplasty), 34.4% (Hydrus), 36.5% (gonioscopically-assisted transluminal trabeculotomy), 24.0% (trabectome), 25.1% (Kahook dual blade), 30.2% (Cypass), 38.8% (XEN), and 50.0% (Preserflo).54 This review provides an excellent historic review of the MIGS procedures and goals of optimal surgical outcomes. They acknowledge that MIGS procedures bring favorable safety profiles and quick postoperative recoveries with a decrease in IOP reduction that is more modest than traditional filtrating surgery. While they have provided clinicians with a wider range of options there is a lack of evidence-based criteria for procedure selection and expected outcomes. The authors acknowledge the current evidence is limited to heterogeneous nonrandomized studies and uncontrolled retrospective comparisons with few quality RCT and lack of comparative studies calling for the needs for carefully designed RCTs.

A 2017 SR and meta-analysis also aimed to compare studies related to the various MIGS procedures. Limiting their review to studies with at least one year follow-up in patients affected by primary open angle glaucoma, pseudoexfoliative glaucoma or pigmentary glaucoma. 21 case series and 9 RCTs met this inclusion from 3,069 studies. Studies were assessed for risk of bias using the Cochrane Risk of Bias and the ROBINS-I tools. In the RCTs risk of bias include lack of blinding, allocation concealment and attrition bias and in the non-RCT patients’ selection, masking of participants and co-intervention management was cited as risk. Evidence to compare MIGS surgery with medical therapy or other MIGS procedures was lacking. The authors conclude “Although MIGS seem efficient in the reduction of the IOP and glaucoma medication and show good safety profile, this evidence is mainly derived from non-comparative studies and further, good quality RCTs are warranted.”⁶⁰

Stent placement without cataract surgery

Sarkisian et al. conducted a prospective, multi-center, single-arm trial evaluating 72 patients with open angle and inadequate response to maximally tolerated medical therapy (n=11) or more conventional incisional or cilioablative procedures (n=61) with baseline IOP of 23.4±2.8 mmHg (range permitted was 20-35 mmHg). The iStent infinite Trabecular Micro-Bypass System was placed as standalone surgery. They reported preoperative mean medicated MDIOP of 23.4±2.8 mmHg and mean reduction (SE) in MDIOP at month 12 of 5.9(0.6) mmHg [5.5(0.7) mmHg Failed-Surgery subgroup, 8.1(0.9) mmHg MTMT subgroup. A total of 76.1% of all enrolled patients met the responder endpoint (73.4% Failed-Surgery, 90.9% MTMT), with mean reduction (SE) in MDIOP at month 12 of 5.9(0.6) mmHg [5.5(0.7) mmHg Failed-Surgery subgroup, 8.1(0.9) mmHg MTMT subgroup]. No intraoperative AEs were reported. Postoperatively, no unanticipated adverse device effects and no serious ocular AEs were reported. Device-related AEs that were considered nonserious (n=13 events in 9 eyes).61 Limitations include single imputation method for missing data points (authors note a trial completion rate of 98.6% at 12 months), lost to follow up, two major protocol deviations were noted (glaucoma secondary to elevated episcleral venous pressure in 1 patient, and impaired visualization due to arcus senilis, corneal striae, and external marker location-dye during surgery in another patient), short follow up of 12 months, lack of medication washout protocol potentially causing undo risk and risk of bias.

A systematic review and meta-analysis included 13 studies, 4 randomized control trials and 9 nonrandomized or single arm studies with accumulative data for 778 eyes, addressing standalone trabecular micro bypass glaucoma surgery with iStent aqueous stent devices in patients with OAG. The authors reported a weighted mean IOP reduction of 31.1% at 6 and 12 months with similar ranged reduction in the studies that reported up to 60 months. They also reported a reduction in medication burden by approximately one medication up to a 60 month endpoint.⁶² Limitations of this analysis include combining randomized control trials and perspective case series into the same analysis. Additionally, there were a wide variety of comparators (when comparators were present), variability in the baseline patient characteristics, medication use, type of device used, the number of stents, duration of follow-up, lack of control and randomization in the case series, significant risk of bias creating broad heterogeneity and making the conclusion from this analysis of uncertain reliability. The most valuable input from the analysis was lack of harm noted from the standalone insertion of the device.
In direct comparison of Hydrus and iStent without cataract extraction, moderate-certainty evidence showed Hydrus lowered IOP by 3.1 mmHg (95% CI, 2.0 to 4.2 mmHg; estimate based on 1 trial) more than iStent alone.²²

Societal Guidance

The American Academy of Ophthalmology (AAO) Technology Assessment on Aqueous Shunts in Glaucoma concludes, based on Level I evidence, aqueous shunts seem to have benefits, such as IOP control and duration of benefit, and are comparable to trabeculectomy in the management of complex glaucoma. Too few high-quality direct comparisons of the various available shunts have been published to assess relative efficacy or complications of specific devices and additional comparative studies are encouraged.⁶³

The American Academy of Ophthalmology (AAO) Technology Assessment of Novel Glaucoma Procedures reviewed 23 relevant publications on novel or emerging surgical techniques for the treatment of OAG. They conclude that these devices show some promise as an alternative treatment to reduce IOP for OAG however it is not yet possible to conclude whether these novel procedures are superior, equal to or inferior to surgery such as trabeculectomy or to one another. Additional research is needed.⁶

The 2022 AAO Summary Benchmarks for Preferred Practice Pattern Guidelines whose recommendations are defined by Grading of Recommendation Assessment, Development and Evaluation (GRADE) concludes³:

• Target IOP is an estimate and must be individualized and/or adjusted during the course of disease.
• The initial target pressure is set at least 25% lower than pretreatment IOP
• IOP can be lowered by medical treatment, laser therapy or incisional surgery (alone or in combination)
• Medical therapy presently is the most common initial intervention to lower IOP
• If progression occurs at the target pressure, undetected IOP fluctuations and adherence to the therapeutic regimen and recommendations for therapeutic alternatives should be discussed before adjusting target IOP downwards

American Academy of Ophthalmology’s Glaucoma Preferred Practice Pattern states that while several other glaucoma surgeries exist as alternatives to trabeculectomy or aqueous shunt implantation the precise role of these procedures is yet to be determined. They identify several MIGS techniques for which evidence is scarce: Kahook Dual Blade (New World Medical), Goniotome (NeoMedix Corp), gonioscopy-assisted transluminal trabeculotomy, and ab interno canaloplasty.¹

According to the 2015 AAO POAG Preferred Practice Pattern (PPP), the “potential benefits of a combined procedure (cataract extraction with 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.”⁶⁴ Per the SMEs it has become standard to offer IOP reduction at the time of cataract surgery for those with elevated IOP as the benefits outweigh the risk and it is consistent with AAO recommendations. American Academy of Ophthalmology’s Glaucoma Preferred Practice Pattern states that while several other glaucoma surgeries exist as alternatives to trabeculectomy or aqueous shunt implantation the precise role of these procedures is yet to be determined. Multiple studies including randomized controlled trials and systematic review with meta-analysis have shown the minimally invasive surgical approach with aqueous stents placement has been shown to accomplish reduction in IOP and potentially reduce the risk of vision loss secondary to glaucoma.

In summary, this contractor considers one iStent, iStent inject, istent inject W, or Hydrus device per eye medically reasonable and necessary for the treatment of adults with mild or moderate open-angle glaucoma 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. One study²³ supports the role of additional stent’s providing further reduction in intraocular pressure. However, this is limited data and therefore the number of stents allowed will be consistent with the stents contained within the device. Multiple stents (so-called “dosing"), regardless of method is not supported by sufficient evidence.

The XEN45 device received 510K clearance based on having a similar mechanism (subconjunctival pathway) as “gold standard” filtration procedure (trabeculectomy and tube shunts), demonstrating “substantial equivalence” in the pivotal prospective study of patients with refractory glaucoma.¹⁸ 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.”⁶⁵ In addition, the American Glaucoma Society (AGS), the New York State Ophthalmological Society (NYSOS), and numerous glaucoma experts wrote CGS 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.”

The contractor considers one 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 mmHg) 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.

The iStent Infinite® device received 510(k) clearance with an indication for use to reduce the intraocular pressure of the eye for adult patients with primary open-angle glaucoma and is considered reasonable and necessary to be performed in conjunction with cataract surgery or as a standalone procedure in whom previous medical and surgical treatment has failed. Given the challenges of treating this patient population and the positive outcome seen in the randomized controlled trial⁶⁵ this contractor will consider one device per eye reasonable and medically necessary for refractory glaucoma as defined above.

The SMEs are enthusiastic about new innovations providing additional treatment options for patients. They acknowledge evidence is lagging and welcome further studies but feel that there are barriers to randomized controlled trials and comparative studies. They acknowledge the potential impact bias may have within the papers but feel that they can be adequately assessed.

While multiple approaches for minimally invasive glaucoma surgery have emerged, there is a lack of data to understand the role of these procedures in adult glaucoma management and how this compares to standard of care medical and surgical treatment options.

• Goniotomy is well studied as first line management for pediatric glaucoma, but adult studies for open angle glaucoma (a different etiology) are lacking and with mixed results so there is minimal literature to support goniotomy in the adult population.
• The body of literature supporting these technologies is low quality consisting largely of retrospective studies and case series there are few to no RCTs and no high-quality evidence to support these procedures. This is summarized by the following:

• • Ab interno trabecular bypass surgery (gonitomy) has emerged as an alternative to trabeculotomy in effort to reduce IOP in OAG patients while reducing risk of complications related to trabeculotomy. The evidence to support these procedures consists of case reports, case series, retrospective reviews and one RCT with only 10 patients in the treatment arm with short term follow-ups.

• • A meta-analysis on the Tracebetome was conducted but was fraught with significant heterogeneity, limited by low-quality evidence, lack of clear definition for glaucoma, variable outcome and duration of follow-up questioning the reliability of this conclusion.³¹

• • The role of insertion of aqueous shunts at the time of these procedures has not been established.
  • A 2021 Cochrane Review of randomized controlled trials to evaluate safety and efficacy of ab interno trabecular bypass surgery with Trabectome for open angle glaucoma conclude there is no high-quality evidence for the outcome of ab interno trabecular bypass surgery with Trabectome for open angle glaucoma calling for the need for properly designed randomized controlled trials.²⁸
  • Gonioscopy-assisted transluminal trabeculotomy (GATT) and Ab Interno Canaloplasty (ABiC) are supported by low quality evidence consisting of case series and retrospective reviews making up the body of literature. There are no comparison studies, understanding of the role in conjunction with cataract surgery or the application of shunts or long-term outcomes reported.
    
    
  • Canaloplasty in combination with trabeculotomy ab interno (e.g., OMNI® Surgical System) is supported by several retrospective studies and one prospective study which is limited by lack of randomization and controls, short-term data, and risk of bias.
  • Case series and retrospective reviews address phacoviscocanalostomy, however meta-analysis shows inferiority to trabeculectomy and uncertain long-term outcomes.-
  • Studies comparing the various MIGS procedures to trabeculotomy or aqueous stents are necessary to determine which procedures may be most appropriate for selecting patients, long-term outcomes with the most risk reduction possible to benefit the patients.

• Many of the study population have baseline IOP in the high teens (below the threshold of elevated IOP as define by IOP >21 mm Hg) and while it is established that patients with POAG can have disease with IOP’s within the normal range and the potential benefit for early intervention the threshold for intervention is not fully established. AAO and established guidelines support medical management in this population. Many of the MIGS surgical procedures seem to be aimed at reducing the need for eye drops, but the effectiveness as compared to medical management is not established.
• There is concern that the majority of MIGS procedures are not as effective in lowering eye pressure as traditional trabeculotomy and studies thus far show that the intraocular pressure after MIGS procedure typically remains in the low-mid teen range, therefore may not be appropriate for those with advanced glaucoma or those who need lower eye pressures.
• The long-term impact of these procedures and if they affect the outcomes of more definitive glaucoma management procedures in the future has not been established. There is a lack of studies comparing these procedures to medical management, “gold standard” trabeculotomy or each other. While these procedures have been claimed to be safer than traditional trabeculotomy, there are no comparative studies to determine if this is indeed the case. Due to short-term follow-ups the impact these procedures can have on future procedures (such as scar tissue formation/loss of anatomical landmarks) eligibility/effectiveness of future interventions is not established. Studies do not report long-term outcome data and potential future harms is not yet established.
• Patient selection has not been standardized within the studies so appropriate patient selection has not been clearly established.

For a service to be considered “reasonable and necessary” under §1862(a) (1) (A) of the Act it must be furnished in accordance with acceptable standard medical practice for the diagnosis or treatment of the condition.66 To meet this requirement, an intervention must be established and supported by medical literature and cannot be considered experimental or investigational. In this case, there is insufficient evidence to support clear standards for patient selection, established benefit of these procedures over standard of care and how they improve health outcomes for beneficiaries, therefore do not meet these criteria. Without sufficient evidence to support these procedures they are considered investigational.

Documentation Requirements:

The patient's medical record must contain documentation that fully supports the medical necessity for services included within this 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.

N/A

1. Gedde SJ, Vinod K, Wright MM, et al. Primary open-angle glaucoma preferred practice pattern®. Ophthalmology. 2021;128(1):P71-P150.
2. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Archives of ophthalmology. 2002;120(6):701-713.
3. AAO PPP Glaucoma Panel, Hoskins Center for Quality Eye Care. AAO Glaucoma Summary Benchmarks. https://www.aao.org/education/summary-benchmark-detail/glaucoma-summary-benchmarks-2020. Published 2022. Accessed 3/24/2023.
4. Deborah S Jacobs M. Open-angle glaucoma: Treatment. www.uptodate.com. Published 2022. Updated 2/2023. Accessed 3/24/2023.
5. Musch DC, Gillespie BW, Niziol LM, et al. Cataract extraction in the collaborative initial glaucoma treatment study: incidence, risk factors, and the effect of cataract progression and extraction on clinical and quality-of-life outcomes. Archives of ophthalmology. 2006;124(12):1694-1700.
6. Francis BA, Singh K, Lin SC, et al. Novel Glaucoma Procedures: A Report by the American Academy of Ophthalmology. Ophthalmology. 2011;118(7):1466-1480.
7. Won I. Kim AAA, , Daniel B. Moore, , Won I. Kim Canaloplasty. EyeWiki. https://eyewiki.aao.org/Canaloplasty#cite_note-8. Updated 2/10/23. Accessed 3/27/23.
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