Coverage Policy Manual
Policy #: 2010017
Category: Medicine
Initiated: April 2010
Last Review: January 2024
  Aqueous Shunts and Devices for Glaucoma

Description:
Glaucoma surgery is intended to reduce intraocular pressure (IOP) when the target IOP cannot be reached with medications. Due to complications with established surgical approaches such as trabeculectomy, a variety of shunts are being evaluated as alternative surgical treatments for patients with inadequately controlled glaucoma. Microstents are also being evaluated in patients with mild-to-moderate open-angle glaucoma (OAG) currently treated with ocular hypotensive medication.
 
Glaucoma is the leading cause of irreversible blindness worldwide and is characterized by elevated intraocular pressure (IOP). In 2020, glaucoma affected approximately 52.7 million individuals globally, with a projected increase to 79.8 million in 2040 (Allison, 2021). Glaucoma has been reported to be 7 times more likely to cause blindness and 15 times more likely to cause visual impairment in Black individuals as compared to White individuals. In the U.S. in 2010, Black individuals had the highest prevalence rate of primary open angle glaucoma at 3.4% compared to 1.7% among White individuals.
 
In the primary (conventional) outflow pathway from the eye, aqueous humor passes through the trabecular meshwork, 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 and/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.
 
First-line treatment typically involves pharmacologic therapy. Topical medications either increase the aqueous outflow (prostaglandins, alpha-adrenergic agonists, cholinergic agonists, Rho-kinase inhibitors) or decrease aqueous production (alpha-adrenergic agonists, beta-blockers, carbonic anhydrase inhibitors). Pharmacologic therapy may involve multiple medications, have potential side effects, and may be inconvenient for older adults or incapacitated patients.
 
Surgical intervention may be indicated in patients with glaucoma when the target IOP cannot be reached pharmacologically. Surgical procedures for glaucoma aim to reduce IOP from impaired aqueous humor drainage in the trabecular meshwork and/or Schlemm canal. Trabeculectomy (guarded filtration surgery) is the most established surgical procedure for glaucoma, which involves dissecting the conjunctiva, creating a scleral flap and scleral ostomy then suturing down the flap and closing the conjunctiva, allowing aqueous humor to directly enter the subconjunctival space. This procedure creates a subconjunctival reservoir, which can effectively reduce IOP, but commonly results in filtering “blebs” on the eye, and is associated with numerous complications (e.g., hemorrhage, scarring, hypotony, infection, leaks, bleb-related endophthalmitis) and long-term failure.
 
Insertion of shunts from outside the eye (ab externo) is another surgical option to lower IOP. Examples of ab externo devices cleared by the U.S. Food and Drug Administration (FDA) include the Ahmed, Baerveldt, Molteno, and EX-PRESS mini-shunt, which shunt aqueous humor between the anterior chamber and the suprachoroidal space. These devices differ by explant surface areas, shape, plate thickness, presence or absence of a valve, and details of surgical installation. Generally, the risk of hypotony (low pressure) is reduced with aqueous shunts compared with trabeculectomy, but IOP outcomes are worse than after standard guarded filtration surgery. The risk of postoperative infection is lower with shunts than with trabeculectomy, and failure rates are similar (»10% of devices fail annually). The primary indication for aqueous shunts is for failed medical or surgical therapy, although some ophthalmologists have advocated their use as a primary surgical intervention, particularly for selected conditions such as congenital glaucoma, trauma, chemical burn, or pemphigoid.
 
Minimally Invasive Glaucoma Surgeries (MIGS) are alternative, less invasive techniques that are being developed and evaluated. MIGS, which use microscopic-sized equipment and smaller incisions, involves less surgical manipulation of the sclera and the conjunctiva compared with other surgical techniques. There are several categories of MIGS: miniaturized trabeculectomy, trabecular bypass, milder laser photocoagulation, and totally internal or suprachoroidal stents (ab interno). This policy evaluates the placement of ab interno stents. Shunts and stents can be administered through an external flap of the conjunctiva and sclera (ab externo) or in a small incision in the cornea with the devices inserted through the anterior chamber of the eye (ab interno). Some ab interno microstents may be inserted with injectors.
 
Examples of ab externo devices are the Ahmed, Baerveldt, and EX-PRESS shunts. Examples of ab interno devices either approved or given marketing clearance by the FDA include the iStent, which is a 1-mm long stent inserted into the end of the Schlemm canal through the cornea and anterior chamber; iStent inject, and XEN gelatin stent.
 
Because aqueous humor outflow is pressure-dependent, the pressure in the reservoir and venous system is critical for reaching the target IOP. Therefore, some devices may be unable to reduce IOP below the pressure of the distal outflow system used (e.g., <15 mm Hg) and are not indicated for patients for whom very low IOP is desired (e.g., those with advanced glaucoma). It has been proposed that stents such as the iStent, iStent inject, and Hydrus Microstent may be useful in patients with early-stage glaucoma to reduce the burden of medications and problems with compliance. One area of investigation is patients with glaucoma who require cataract surgery. An advantage of ab interno stents is that they may be inserted into the same incision and at the same time as cataract surgery. Also, most devices do not preclude subsequent trabeculectomy if needed. It may also be possible to insert more than one stent to achieve desired IOP.
 
Regulatory Status
 
The first- generation Ahmed™ (New World Medical), Baerveldt® (Advanced Medical Optics), Krupin (Eagle Vision), and Molteno® (Molteno Ophthalmic) ab externo aqueous shunts were cleared for marketing by the FDA through the 510(k) process between 1989 and 1993; modified Ahmed and Molteno devices were cleared in 2006. They are indicated for use “in patients with intractable glaucoma to reduce intraocular pressure where medical and conventional surgical treatments have failed.” The AquaFlow™ Collagen Glaucoma Drainage Device (STAAR Surgical) was approved by the FDA through the premarket approval process for the maintenance of the subscleral space following nonpenetrating deep sclerectomy. In 2003, the ab externo EX-PRESS® Mini Glaucoma Shunt was cleared for marketing by the FDA through the 510(k) process.
 
In 2016, the XEN® Glaucoma Treatment System (Allergan), which consists of the XEN45 Gel Stent preloaded into the XEN Injector, was cleared for marketing by the FDA through the 510(k) process as an ab interno aqueous stent for management of refractory glaucoma. The approval was for patients with refractory glaucoma who failed previous surgical treatment or for patients with primary open-angle glaucoma unresponsive to maximum tolerated medical therapy. The FDA determined that this device was substantially equivalent to existing devices, specifically the Ahmed™ Glaucoma Valve and the EX-PRESS® Glaucoma Filtration Device.
 
In 2018, the first Microstent, iStent® Trabecular Micro-Bypass Stent preloaded into the iStent inject device (Glaukos) was approved by the FDA through the 515(d) process for use in conjunction with cataract surgery for the reduction of IOP in adults with mild-to-moderate open-angle glaucoma currently treated with ocular hypotensive medication.
  
In August 2018, Alcon announced an immediate voluntary recall of the CyPass microstent, which had been approved by the FDA in 2016 for use in conjunction with cataract surgery in adults with mild-to- moderate open-angle glaucoma. The recall was based on five-year postsurgery data from the COMPASS-XT long-term safety study. Results showed a statistically significant increase in endothelial cell loss among patients receiving the CyPass microstent compared with patients receiving cataract surgery alone.
 
Regulatory Status of Aqueous Shunts and Stents:
 
    • AquaFlow™, manufactured by STAAR Surgical, is a Drainage device that received PMA in 2001
    • Ahmed™, manufactured by New World Medical, is an Aqueous glaucoma shunt, ab externo that received 510(k) before 1993
    • Baerveldt®, manufactured by Advanced Medical Optics, is an Aqueous glaucoma shunt, ab externo that received 510(k) before 1993
    • Krupin, manufactured by Eagle Vision, is an Aqueous glaucoma shunt, ab externo that received 510(k) before 1993
    • Molteno®, manufactured by Molteno Ophthalmic, is an Aqueous glaucoma shunt, ab externo that received 510(k) before 1993
    • EX-PRESS®, manufactured byAlcon, is a Mini-glaucoma shunt, ab externo that received 510(k) in 2003
    • XEN® Gel Stent; XEN injector, manufactured by AqueSys/Allergan, is an Aqueous glaucoma stent, ab interno that received 510(k) in 2016
    • iStent®; iStent inject®, manufactured by Glaukos, is a Microstent, ab interno that received 515(d) in conjunction with cataract surgery in 2018
    • iStent supra®, manufactured by Glaukos, is a Suprachoroidal stent that was not approved in clinical trial
    • CyPass®, manufactured by Alcon, is a Suprachoroidal stent, ab interno that the company voluntarily recalled in 2018
    • Hydrus™, manufactured by Ivantis, is a Microstent, ab interno that received PMA approval in 2018
    • Beacon Aqueous Microshunt, manufactured by MicroOptx, is a Micro-Shunt, ab externo that was not approved, in clinical trial
    • PRESERFLO® MicroShunt (previously InFocus), manufactured by Santen, is a Micro-Shunt, ab externo that was not approved, in clinical trial
    • iStent Infinite, manufactured by Glaukos, is a Microstent, ab interno that received 510(k) clearance in August 2022.
 
Coding
 
There is a category I CPT code for insertion of aqueous shunt using an external approach:
 
66183 Insertion of anterior segment aqueous drainage device, without extraocular reservoir, external approach.
 
There are CPT category III codes for these procedures using an internal approach:
 
0191T Insertion of anterior segment aqueous drainage device, without extraocular reservoir; internal approach, into the trabecular meshwork; initial insertion
0376T each additional device insertion (List separately in addition to code for primary procedure)
0253T Insertion of anterior segment aqueous drainage device, without extraocular reservoir; internal approach, into the suprachoroidal space
0449T Insertion of aqueous drainage device, without extraocular reservoir, internal approach, into the subconjunctival space; initial device
0450T each additional device (List separately in addition to code for primary procedure).
 
Effective July 1, 2017, there is a CPT category III code for insertion of the CyPass device:
 
0474T Insertion of anterior segment aqueous drainage device, with creation of intraocular reservoir, internal approach, into the supraciliary space.
 
The category III CPT codes specify insertion of an aqueous drainage device without drainage to an extraocular reservoir and are therefore differentiated from the existing codes for trabeculectomy or placement of shunts that drain to an extraocular reservoir (below). Procedures using the Trabectome device are considered similar to trabecular laser ablation and are not within the scope of this policy.

Policy/
Coverage:
Effective February 2019
 
Meets Primary Coverage Criteria or Is Covered For Contracts Without Primary Coverage Criteria
 
Insertion of ab externo aqueous shunts approved by the U.S. Food and Drug Administration, meets primary coverage criteria that there be scientific evidence of effectiveness as a method to reduce intraocular pressure in patients with glaucoma where medical therapy has failed to adequately control intraocular pressure.
 
Insertion of ab interno aqueous stents approved by the U.S. Food and Drug Administration as a method to reduce intraocular pressure in patients with glaucoma where medical therapy has failed to adequately control intraocular pressure, meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
Implantation of 1 or 2, U.S. Food and Drug Administration approved, ab interno stents in conjunction with cataract surgery in patients with mild-to-moderate open-angle glaucoma treated with ocular hypotensive medication, meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
 Does Not Meet Primary Coverage Criteria or Is Investigational For Contracts Without Primary Coverage Criteria
 
Use of an ab externo aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria, use of an ab externo aqueous shunt for all other conditions, including in patients with glaucoma when intraocular pressure is adequately controlled by medications, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Use of ab interno stents for all other conditions, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria, use of ab interno stents for all other conditions is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective Prior to February 2019
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Insertion of aqueous shunts approved by the U.S. Food and Drug Administration (FDA) as a method to reduce intraocular pressure in patients with glaucoma where medical therapy has failed to adequately control intraocular pressure meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Implantation of up to three FDA-approved micro-stents (e.g., iStent®) in conjunction with cataract surgery in patients who are intolerant of medications meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Implantation of a single FDA-approved CyPass micro-stent (one stent per eye) in conjunction with cataract surgery in patients who are intolerant of medications meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Implantation of a single FDA-approved Xen Gel Stent (one stent per eye) in conjunction with cataract surgery or without cataract surgery in patients who have failed surgical treatment OR have reached maximum response to OR are intolerant of medications for treatment of refractory glaucoma meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications, is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.
 
The use of a micro-stent for all other conditions does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of a micro-stent for all other conditions is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.
 
Implantation of a single FDA-approved Xen Gel Stent for all other conditions does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the implantation of a single FDA-approved Xen Gel Stent for all other conditions is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.
 
The use of a drug-eluting implant for the treatment of glaucoma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria, the use of a drug-eluting implant for the treatment of glaucoma, is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.
 
Effective Prior to August 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Insertion of aqueous shunts approved by the U.S. Food and Drug Administration (FDA) as a method to reduce intraocular pressure in patients with glaucoma where medical therapy has failed to adequately control intraocular pressure meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Implantation of up to three FDA-approved micro-stents (e.g., iStent®) in conjunction with cataract surgery in patients who are intolerant of medications meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Implantation of a single FDA-approved CyPass micro-stent (one stent per eye) in conjunction with cataract surgery in patients who are intolerant of medications meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications, is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.
 
The use of a micro-stent for all other conditions does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of a micro-stent for all other conditions is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.
 
The use of a drug-eluting implant for the treatment of glaucoma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria, the use of a drug-eluting implant for the treatment of glaucoma, is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.
 
Effective March 2015 – October 2016
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Insertion of aqueous shunts approved by the U.S. Food and Drug Administration (FDA) as a method to reduce intraocular pressure in patients with glaucoma where medical therapy has failed to adequately control intraocular pressure meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Implantation of up to three FDA-approved micro-stents (e.g., iStent®) in conjunction with cataract surgery in patients who are intolerant of medications meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications, is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.
 
The use of a micro-stent for all other conditions does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of a micro-stent for all other conditions is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.
 
The use of a drug-eluting implant for the treatment of glaucoma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness. For members with contracts without primary coverage criteria, the use of a drug-eluting implant for the treatment of glaucoma, is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.
 
Effective September 2013 – February 2015
  
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Insertion of aqueous shunts approved by the U.S. Food and Drug Administration (FDA)  as a method to reduce intraocular pressure in patients with glaucoma where medical therapy has failed to adequately control intraocular pressure meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Implantation of up to three FDA-approved micro-stents (e.g., iStent®) in conjunction with cataract surgery in patients who are intolerant of medications meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications, is considered investigational.  Investigational services are exclusions in most member benefit certificates of coverage.
 
The use of a micro-stent for all other conditions does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of a micro-stent for all other conditions is considered investigational.  Investigational services are exclusions in most member benefit certificates of coverage.
 
Effective September 2011 – August 2013
Insertion of aqueous shunts approved by the U.S. Food and Drug Administration (FDA)  as a method to reduce intraocular pressure in patients with glaucoma where medical therapy has failed to adequately control intraocular pressure meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications, is considered investigational.  Investigational services are exclusions in most member benefit certificates of coverage.
 
Canaloplasty meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes as a method to reduce intraocular pressure in patients with chronic primary open-angle glaucoma under the following conditions:
 
    • Medical therapy has failed to adequately control intraocular pressure, AND
    • The patient is not a candidate for any other intraocular pressure lowering procedure (e.g. trabeculectomy or glaucoma drainage implant) due to a high risk for complications.
 
Canaloplasty as a method to reduce intraocular pressure in all other conditions, including but not limited to, angle-closure glaucoma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, canaloplasty as a method to reduce intraocular pressure in all other conditions, including but not limited to, angle-closure glaucoma is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.
 
Effective prior to September 2011
 
Insertion of aqueous shunts approved by the U.S. Food and Drug Administration (FDA)  as a method to reduce intraocular pressure in patients with glaucoma where medical therapy has failed to adequately control intraocular pressure meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Use of an aqueous shunt for all other conditions, including patients with glaucoma when intraocular pressure is adequately controlled by medications, is considered investigational.  Investigational services are exclusions in most member benefit certificates of coverage.
 
Canaloplasty does not meet primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Canaloplasty is considered investigational as a method to reduce intraocular pressure in patients with glaucoma. Investigational services are exclusions in most member benefit certificates of coverage.
 

Rationale:
“Due to the detail of the rationale, the complete document is not online. If you would like a hardcopy print, please email: codespecificinquiry@arkbluecross.com
 
 
FDA-Approved/Cleared Aqueous Shunts
A 2006 Cochrane review evaluated 15 randomized or pseudo-randomized controlled trials (RCTs), with a total of 1,153 participants, on the Ahmed, Baerveldt, Molteno, and Schocket shunts (Minckler, 2006).  Trabeculectomy was found to result in a lower mean IOP (by 3.8 mmHg) than the Ahmed shunt at 1 year. A limitation of this report is that complications were not compared, as the authors considered them to be too variably reported to allow comparative tabulation. There was no evidence of superiority of one shunt over another.
 
A literature review on commercially available aqueous shunts, including the Ahmed, Baerveldt, Krupin, and Molteno devices, for an American Academy of Ophthalmology (AAO) technology assessment was published in 2008 (Minckler, 2008).   This review indicated that the IOP will generally settle at higher levels (approximately 18 mmHg) with aqueous shunts than after standard trabeculectomy (14-16 mmHg) or after trabeculectomy with anti-fibrotic agents 5-fluoracil or mitomycin C (8-10 mmHg). In 1 study, mean IOPs with the Baerveldt shunt and adjunct medications were found to be equivalent to trabeculectomy with mitomycin C (13 mmHg). Five-year success rates for the two procedures were found to be similar (50%). The assessment concluded that aqueous shunts were comparable with trabeculectomy for IOP control and duration of benefit. The risk of postoperative infection was less with aqueous shunts than after trabeculectomy. Complications of aqueous shunts were noted to include: immediate hypotony after surgery; excessive capsule fibrosis and clinical failure; erosion of the tube or plate edge; strabismus; and, very rarely, infection. The most problematic long-term consequence of anterior chamber tube placement was described as accelerated damage to the corneal endothelium over time.
 
Implantation of the Ex-PRESS mini shunt under a scleral flap was compared with standard trabeculectomy in a randomized study of 78 patients (80 eyes) with a diagnosis of open-angle glaucoma that could not be controlled with maximal-tolerated medical therapy (de Jong, 2009).  The 2 groups were similar after randomization, with the exception of difference in the mean age (62 years for the Ex-PRESS group and 69 years for the trabeculectomy group). At an average 12 months’ follow-up, mean IOP had improved from 23 to 12 mm Hg in the Ex-PRESS group and from 22 to 14 mm Hg in the trabeculectomy group. Both groups of patients used fewer antiglaucoma medications postoperatively than before the procedure (from 2.8 at baseline to 0.3 in the Ex-PRESS group and from 3.0 at baseline to 0.6 in the trabeculectomy group). Twelve-month Kaplan-Meier success rates (defined as an IOP of >4 mm Hg or <18 mm Hg without use of antiglaucoma medications) were 82% for the Ex-PRESS shunt and 48% for trabeculectomy. There was a similar level of postoperative complications in the two groups.
 
One year results from the iStent U.S. investigational device exemption (IDE) open-label 29 site multicenter randomized clinical trial were reported to the FDA in 2010 and published in 2011 (Samuelson, 2011). The objective of the trial was to measure the incremental effect on IOP from iStent implantation over that of cataract surgery alone and to determine the potential benefit of combining 2 therapeutic treatments into 1 surgical event. A total of 240 patients (mean age of 73 years) with cataracts and mild to moderate open-angle glaucoma (IOP < 24 mm Hg controlled on 1 to 3 medications) were randomized to undergo cataract surgery with iStent implantation or cataract surgery only. The mean number of medications at baseline was 1.5. The medicated IOP at baseline was 18.7 mm Hg in the stent group and 18.04 in the control group. After washout, the mean IOP was 25 mm Hg and mean visual acuity (logMAR) was 0.36. Follow-up visits were performed at 1, 3, 6, and 12 months. Results were assessed by intent-to-treat analysis with the last observation carried forward and per protocol analysis. Of the 117 subjects randomized to iStent implantation, 111 underwent cataract surgery with stent implantation, and 106 (91%) completed the 12-month postoperative visit. Of the 123 subjects randomized to cataract surgery only, 117 underwent cataract surgery and 3 exited the study because of complications of cataract surgery. Of the remaining 114 subjects, 112 (91%) completed the 12-month visit. The proportion of eyes meeting both the primary (unmedicated IOP <21 mm Hg) and secondary outcomes (IOP reduction >20% without hypotensive medications) was higher in the treatment group than in the control group at every visit. At 1-year follow-up, 72% of treatment eyes and 50% of control eyes achieved the primary efficacy endpoint. The proportion of patients achieving the secondary efficacy endpoint was 66% in the treatment group versus 48% in the control group. Ocular hypotensive medications were initiated later in the postoperative period and used in a lower proportion of patients in the treatment group at every postoperative interval (e.g., 15% vs. 35% at 12 months). The mean reduction in IOP was similar in the 2 groups, with a higher level of medication used in the control group (mean of 0.4 medications) in comparison with the treatment group (0.2 medications). The overall incidence of adverse events was similar between the groups.
 
Aqueous Shunts Not Approved by the FDA
The published literature on non-FDA approved/cleared aqueous drainage devices consists of small case series on the iStent and EyePass (Spiegel, 2007) (Dietlein, 2008).   A search of aqueous shunts and glaucoma in www.clinicaltrials.gov during 2008 and 2009 found a number of clinical trials in progress. The iStent was being studied under an FDA category B investigational device exemption. Neither  the iStent or EyePass had undergone FDA approval/clearance.
 
Transluminal Dilation (Canaloplasty)
 
Lewis et al reported interim data analysis from a company-sponsored multicenter safety/efficacy study on canaloplasty using the iTrack microcatheter (Lewis, 2007).  Catheterization of the canal was achieved in 83 of 94 patients enrolled (88%); tension sutures were successfully placed in 74 patients (79%) with a mean IOP of 24 mm Hg. At 3-month follow-up, 57 patients (77% of 74 implanted) had an IOP of 16 mm Hg, and at 12 months 48 patients (65%) had a mean IOP of 15 mm Hg. Ten ocular adverse events (11%) were reported, including hyphema (3%), elevated IOP (3%), Descemet’s membrane detachment, hypotony, choroidal effusion, and exposed closure suture (1% each). Eleven patients (12%) had a subconjunctival bleb, 6 of which resolved by 3 months. The study design included 5-year follow-up. These results were limited by the lack of randomization and high loss to follow-up.
 
Interim 1-year results from a company-sponsored multicenter study were reported for 40 patients who had combined canaloplasty and cataract surgery (Shingleton, 2008).   Inclusion criteria included: a glaucoma diagnosis of primary open-angle glaucoma (POAG), pigmentary glaucoma, exfoliation glaucoma, or POAG with narrow but not occludable angles after laser iridectomy; a treated IOP of 16 mm Hg or higher at baseline; and a historical untreated IOP of 21 mm Hg or higher. Of the 54 eyes enrolled, successful circumferential catheterization was achieved in 44 eyes (81%) and sutures were successfully placed in 40 eyes (74%). The 14 eyes (26%) that did not have sutures placed were due to the microcatheter entering a collector channel or meeting other resistance during catheterization; successful suture placement was reported to increase with surgeon experience. Two eyes were considered failures, with 1 conversion to trabeculectomy. Clinical results were reported for 25 patients (46% of 54) who were both due for and reported for 12-month follow-up. Of these, 3 eyes (12%) had low subconjunctival blebs at 12 months. No case of suture erosion through the trabecular meshwork or sclera was noted during follow-up. IOP was reduced from a mean of 24 mm Hg to 13 mm Hg at 6 months (reported for 42 eyes; 40 were reported to be successfully treated) and remained under 14 mm Hg in the 25 patients who were evaluated at 12 months. The number of antiglaucoma medications decreased from a mean of 1.5 medications to a mean of 0.1 at 1 month and 0.2 at 12 months. This trial is ongoing, and longer follow-up on a larger number of patients is needed.
 
The American Academy of Ophthalmology (AAO) published a 2008 technology assessment on commercially available aqueous shunts, including the Ahmed, Baerveldt, Krupin, and Molteno devices (Minckler, 2008).  The assessment indicated that in general, the IOP will settle at higher levels (approximately 18 mm Hg) with shunts than after standard trabeculectomy (14–16 mm Hg). Five year success rates of 50% have been found for the two procedures, indicating that aqueous shunts are comparable with trabeculectomy for IOP control and duration of benefit. (based on level I evidence; well-designed randomized controlled trials). The assessment indicated that although aqueous shunts have been generally reserved for intractable glaucoma when prior medical or surgical therapy has failed, indications for shunts have broadened (based on level III evidence; case series, case reports, and poor-quality case-control or cohort studies). The AAO concluded that based on level I evidence, aqueous shunts offer a valuable alternative to standard filtering surgery or to cyclodestructive therapy for many patients with refractory glaucoma.
 
Summary
 
Randomized controlled trials have shown that the use of shunts results in success rates at least as good as standard filtering surgery, with similar complication rates.
 
Other studies have reported use of shunts in patients with both cataracts and less advanced glaucoma, where the IOP is at least partially controlled with medication. Results from these studies indicate that IOP may be lowered below baseline with decreased need for medication in some patients, but complications may lead to trabeculectomy within 6 months in a number of eyes. Since it cannot be determined whether trabeculectomy would have been required had these patients remained on medical therapy, randomized controlled trials with longer follow-up are needed to compare clinical outcomes from patients who have undergone cataract surgery combined with device placement or with continued medical management. In addition, the Trabectome study group reports that 3% of patients required subsequent glaucoma surgery following combined Trabectome/cataract surgery in a large series (Francis, 2008) (Minckler, 2008).  Therefore, comparative trials with the Trabectome would help to evaluate whether device placement provides a health benefit over an ab interno surgical procedure that does not require permanent device implantation.
 
2011 Update
Lewis et al. reported 2-year and 3-year results from the multicenter study in 2009 and 2011, respectively (Lewis, 2009) (Lewis, 2011). Enrolled in the follow-up study were 157 patients with a diagnosis of primary open-angle glaucoma, pigmentary glaucoma, exfoliative glaucoma, and a baseline IOP of 16 mm Hg or higher before surgery, with a historical IOP of 21 mm Hg or higher. Exclusion criteria were neovascular disease, uveitis, peripheral anterior synechiae, angle recession, and developmental or secondary glaucoma (except for pigmentary and exfoliative glaucoma). At baseline, the mean IOP was 23.8 and patients were on an average 1.8 medications; 21% of eyes were on 3 or more antiglaucoma medications, and 12 eyes (7.6%) were on no medications. Twenty-five eyes (15.9%) were pseudophakic. Canaloplasty (with or without cataract surgery) was successful in 133 eyes (85%). Eyes that did not have placement of a tensioning suture were viscodilated to the extent possible by catheterizing the canal from both ostia. At 3 years postoperatively, 134 study eyes (85% follow-up) had a mean IOP of 15.2 mm Hg and mean glaucoma medication use of 0.8 medications; 4 eyes (3%) were on 3 or more antiglaucoma medications, and 66 eyes (49.3%) were on no medications. Another 7 patients (4.4%) had additional glaucoma surgery. Six eyes lost 2 or more lines of corrected visual acuity related to glaucoma progression. With qualified success defined as achieving IOP of 18 mm Hg or lower (with 0 to 2 medications), success was achieved in 69 of the 89 eyes (77.5%) that had successful suture implantation alone and 24 of the 27 eyes (89%) with successful suture placement combined with phacoemulsification. Early surgical/postoperative complications included microhyphema (12%), hyphema (10%), elevated intraocular pressure (6%), Descemet membrane detachment (3%), suture extrusion (1%), and hypotony (1%). Late postoperative complications included cataract (12.7%), transient IOP elevation (6.4%), and partial suture extrusion through the trabecular meshwork (0.6%).
 
Koerber et al. reported on 15 of the patients who participated in the multicenter trial described above who had bilateral POAG and received canaloplasty in one eye and viscocanalostomy in the contralateral eye (Koerber, 2011). Qualifying preoperative IOPs were 18 mm Hg or greater with historical IOPs of at least 21 mm Hg. For the canaloplasty eye, the baseline IOP averaged 26.5 mm Hg on 2.1 medications. All patients had successful suture placement. Follow-up at 18 months showed IOP of 14.5 on 0.3 medications. For the viscocanalostomy eye, the baseline eye averaged 24.3 mm Hg on 1.9 medications; follow-up at 18 months showed an average IOP of 16.1 on 0.4 medications. The reduction in IOP from baseline was significantly greater with canaloplasty (12.0 mm Hg) than with viscocanalostomy (8.2 mm Hg). There was no loss in visual acuity and no adverse events from either procedure. The authors noted that this study effectively compares the additional effects of the 2 major additional maneuvers associated with canaloplasty: first, 360 degrees viscodilation of Schlemm’s canal, as opposed to partial dilation achieved with viscocanalostomy, and second, prolonged opening and tensioning of Schlemm’s canal with suture placement.
 
Grieshaber et al. reported a prospective series of 60 consecutive black South African patients with POAG who underwent canaloplasty (Grieshaber, 2010). The mean preoperative IOP was 45 mm Hg. At 12 month follow-up, the IOP was 15 mm Hg (n=54), and at 36 months, the IOP was 13.3 mm Hg (n=49). Eleven patients (18%) were lost to follow-up at 3 years. With qualified success defined as achieving IOP of 21 mm Hg or lower (with or without medications), success was achieved in 40 of 49 patients (82%). When defined as an IOP of 16 mm Hg or less without medications, 47% of eyes met criteria for complete success. There were no severe complications in this series.
 
Mosaed and colleagues published a comparative effectiveness review of newer (Trabectome and canaloplasty) and older (trabeculectomy and Baerveldt shunt) surgeries for glaucoma in 2009 (Mosaed, 2009). Twelve-month outcomes (intracocular pressure adjunctive medications and complications) were compared after glaucoma-only and combined glaucoma-phacoemulsification surgeries. The review found that Trabectome and canaloplasty provided modest IOP reduction (to about 16 mm Hg) with minimal intraoperative or postoperative complications. Results of Baerveldt glaucoma implant IOP reduction were comparable to trabeculectomy (about 12 mm Hg), but typically this shunt required more postoperative IOP-lowering medication (average of 1.3 vs. 0.5 medications, respectively) to achieve a success rate comparable to trabeculectomy. Patients treated with Trabectome required more medications (average of 1.5) to control IOP than patients treated with canaloplasty (average of 0.6). The authors concluded that Trabectome and canaloplasty are reasonable surgical therapy choices for patients in which IOPs in the mid-teens seem adequate; although trabeculectomy remains the most effective IOP-lowering procedure, it also has the highest serious complication rates.
 
A search of the online site: Clinicaltrials.gov in August 2011 found 2 randomized trials comparing canaloplasty to trabeculectomy. Both studies (NCT01228799 and NCT00854256) are expected to enroll 60 subjects with completion in 2012.
 
In summary, recently, positive 2- to 3-year outcomes have been reported for canaloplasty, along with a systematic review that found that Trabectome and canaloplasty provided modest IOP reduction (to about 16 mm Hg) with minimal intraoperative or postoperative complications. When combined with expert opinion, evidence is sufficient to consider canaloplasty in the subset of patients for whom medical therapy has failed to adequately control intraocular pressure and in whom other surgical procedures (e.g. trabeculectomy or a glaucoma drainage implant) are contraindicated.
 
2012 Update
A literature search was conducted using the MEDLINE database through July 2012.  The key identified literature is summarized below.
 
A comparative effectiveness review (CER) on glaucoma treatments was prepared by the Johns Hopkins Evidence-based Practice Center for the Agency for Healthcare Research and Quality (AHRQ) in 2012 (Boland, 2012). The CER found that the data available on the role of aqueous drainage devices in open-angle glaucoma (primary studies, systematic review) were inadequate to draw conclusions on the comparative effectiveness of these treatments in comparison with laser and other surgical treatments.
 
A 2011 technology assessment from the AAO (literature search up to October 2009) reviewed the evidence on novel, or emerging, glaucoma procedures (Francis, 2011).  Included in the technology assessment were devices and procedures that either had FDA clearance or were in phase III clinical trials in the U.S. at the time. These included the Ex-PRESS™ mini glaucoma shunt, the SOLX Gold Shunt, and the iStent, along with various surgical procedures. The technology assessment concluded that these techniques and devices are still in the initial state (<5 years) of clinical experience and lacking widespread use. The clinical studies generally provided only level III evidence in support of the procedures. Based on the literature available at the time, it was not possible to conclude if the novel procedures were superior, equal to, or inferior to surgery such as trabeculectomy or to one another.
 
The U.K.’s National Institute for Health and Clinical Excellence provided guidance on trabecular stent bypass microsurgery for open angle glaucoma in 2011 (NICE, 2011). The guidance states that current evidence on trabecular stent bypass microsurgery for open angle glaucoma raises no major safety concerns. There is evidence of efficacy in the short term, but this is based on small numbers of patients. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.
 
On June 25, 2012, the iStent (Glaukos) received FDA 510(K) marketing clearance for use in conjunction with cataract surgery for the reduction of intraocular pressure (IOP) in adult patients with mild to moderate open-angle glaucoma who are currently treated with ocular hypotensive medication. Information regarding the iStent was moved to the section of the rationale for FDA-Approved/Cleared Aqueous Shunts.
 
2013 Update
This policy is being updated with a literature search using the MEDLINE database through August 2013. Information addressing canaloplasty is moved to policy #2011064.
 
FDA-Approved/Cleared Aqueous Shunts
 
Baerveldt Glaucoma Shunt
In 2012, Gedde et al. reported 5-year follow-up from the Tube Versus Trabeculectomy (TVT) study (Gedde, 2012). The study included 212 eyes of 212 patients (18-85 years) who had previous trabeculectomy and/or cataract extraction with intraocular lens implantation and uncontrolled glaucoma with IOP of 18 mm Hg or greater and 40 mm Hg or lower on maximum tolerated medical therapy. Excluding patients who had died, the study had 82% follow-up at 5 years, with a similar proportion of patients in the tube and trabeculectomy groups. At 5 years, neither IOP (14.3 mm Hg in the tube group and 13.6 mm Hg in the trabeculectomy group) nor number of glaucoma medications (1.4 in the tube group and 1.2 in the trabeculectomy group) were significantly different with intent-to-treat analysis. The cumulative probability of failure over the 5 years was lower in the tube group than the trabeculectomy group (29.8% vs. 46.9%), and the rate of reoperation was lower (9% vs. 29%). The rate of loss of 2 or more lines of visual acuity was similar in the 2 groups (46% in the tube group and 43% in the trabeculectomy group).
 
 
iStent
At 2-year follow-up, there were 199 of the original 239 patients (83%) remaining in the study. The primary endpoint, IOP of 21 mm Hg or less without use of medication, was reached by 61% of patients in the treatment group compared to 50% of controls (p=0.036) (Craven, 2012). The secondary outcomes of IOP reduction of 20% or more without medication (53% vs. 44%) and mean number of medications used (0.3 vs. 0.5) were no longer significantly different between the groups at 2 years. As noted by the FDA, this study was conducted in a restricted population of patients who had an unmedicated IOP of 22 mm Hg or higher and 36 mm Hg or lower. The results of this study indicate that treatment of this specific population with a microstent is likely to improve outcomes at 1 year compared to cataract surgery alone. However, given the 2-year results of this study, it is not possible to conclude with certainty that health outcomes are improved at longer periods of follow-up.
 
In 2010, Fea reported a randomized double-blind clinical trial of cataract surgery with or without iStent implantation (2:1 ratio) in 36 patients (Fea, 2010). Inclusion criteria were a previous diagnosis of primary open-angle glaucoma with an IOP above 18 mm Hg at 3 separate visits, and on 1 or more hypotensive medications. The stent was implanted using the same small temporal clear corneal incision (approximately 3.0 mm) that had been used for phacoemulsification and intra-ocular lens placement and was guided into Schlemm’s canal by an applicator and ab interno gonioscopy. Follow-up visits with investigators who were masked to the treatment condition were conducted at 24 hours, 1 week, and 1, 2, 3, 6, 9, 12, and 15 months. Prescription of hypotensive medications was performed according to pre-set guidelines. Primary outcomes were IOP and reduction in medication use over 15 months and IOP after a 1-month washout of ocular hypotensive agents (16 months postoperatively). At baseline, IOP was an average of 17.9 mm Hg with 2.0 medications in the stent group and 17.3 mm Hg with 1.9 medications in the control group. The mean IOP at 15 months was 14.8 mm Hg, with 0.4 medications in the stent group and 15.7 mm Hg with 1.3 medications in the control group. Eight patients in the stent group (67% of 12) and 5 in the control group (24% of 21) did not require ocular hypotensive medication. The authors commented that patient compliance is an ongoing concern for most ophthalmologists; therefore, a main goal is to keep the patient as free as possible from medications postoperatively. After washout of medications, mean IOP was 16.6 in the stent group and 19.2 in the control group. Two stents were malpositioned, but one of these appeared to be functioning, and there were no reported adverse events related to stent implantation. This small study suggests that without hypotensive medication, the iStent lowers IOP by about 2.5 mm Hg beyond that generated by cataract surgery alone (approximately 25% decrease in the risk of glaucomatous progression).
 
Use of multiple iStents in combination with cataract surgery was reported in an open-label prospective series of 53 eyes (47 patients) in 2012 (Belovay, 2012). Of the 53 eyes, 28 had implantation of 2 stents and 25 had implantation of 3 stents, based on the need for greater IOP control, as determined by the operating surgeon. Best-corrected visual acuity (BCVA) improved or remained stable in 89% of eyes. IOP decreased from a mean of 18.0 m Hg to 14.3 mm Hg, and the number of hypotensive medications decreased from a mean of 2.7 to 0.7 at 1 year postoperatively. Target IOP was reached in 77% of eyes, while 59% of patients discontinued use of all medications in the study eye. At 1 year, the mean number of hypotensive medications decreased to 1.0 in the 2-stent group and 0.4 in the 3-stent group. Medication use had been stopped in 46% of eyes in the 2-stent group compared to 72% in the 3-stent group. Stent blockage occurred in the early postoperative period in 15% of eyes and was successfully treated with laser.
 
The policy statement is changed to included a coverage statement addressing the use of the iStent.
 
Aqueous Shunts and Stents Not Approved by the FDA
Case series has been identified on the EyePass and CyPass micro-stent (Dietlein, 2008; Hoeh, 2013). The CyPass has not received FDA approval/clearance at this time. The EyePass is no longer being developed.
 
Practice Guidelines and Position Statements
A 2012 position statement by the American Glaucoma Society (AGS) states that new technology whose intraocular pressure-lowering effect allows for a reduction in medications, or a reduction in the need for more advanced surgical care, or improves patient adherence to care, would provide advantages to glaucoma patients (AGS, 2012). If effective and safe, the AGS believe that these benefits and the fact that these technologies will not have bleb-related complications would represent an “improvement in net health outcomes.” In addition, the AGS states that some categories of new surgical devices and techniques are utilized at the time of concomitant cataract surgery. Since cataract surgery alone has been shown to lower intraocular pressure, a control group of patients with similar entry criteria undergoing cataract surgery alone may be appropriate for these technologies.
 
2014 Update
 
A literature search conducted through August 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Ex-PRESS Mini Shunt
A 2014 publication described a U.S. multicenter randomized trial of trabeculectomy compared with EX-PRESS® implantation in 120 patients (120 eyes) (Netland, 2014).The groups were comparable at baseline, with a preoperative IOP of 25.1 mm Hg on a mean of 3.1 medications for the EX-PRESS® group, compared with 26.4 mm Hg on a mean of 3.1 medications in the trabeculectomy group. Throughout 2 years of follow-up after surgery, the average IOP and number of medications were similar in the 2 groups. At 2 years, mean IOP was 14.7 mm Hg on 0.9 medications in the EX-PRESS® group and 14.6 mm Hg on 0.7 medications in the trabeculectomy group. Surgical success was 90% and 87% at 1 year and 83% and 79% at 3 years in the EX-PRESS® and trabeculectomy groups, respectively. Visual acuity returned to near baseline levels at 1 month after EX-PRESS® implantation and 3 months after trabeculectomy (p=0.041), with a median time to return to baseline vision of 0.7 months and 2.2 months, respectively. Postoperative complications were higher after trabeculectomy (41%) than after EX-PRESS® implantation (18.6%).
 
Five-year follow-up was reported in 2011 (de Jong, 2011). At 5 years, the success rates were not significantly different between the 2 groups. In the EX-PRESS® group, IOP remained stable from year 1 (12.0 mm Hg) to year 5 (11.5 mm Hg), while in the trabeculectomy group, IOP decreased from year 3 (13.5 mm Hg) to year 5 (11.3 mm Hg). There were more complications after trabeculectomy than after EX-PRESS® implantation.
 
iStent inject®
An industry-sponsored multicenter unblinded randomized trial compared implantation of 2 iStent inject® devices versus 2 ocular hypotensive agents (Fea, 2014). The 192 patients enrolled in this unmasked trial had an IOP that was not controlled by 1 hypotensive medication. At 12-month follow-up, the 2 groups were comparable for IOP reduction of at least 20%, IOP of 18 mm Hg or less, and mean decrease in IOP. A greater proportion of patients in the iStent inject® group achieved an IOP reduction of at least 50% (53.2% vs 35.7%). One patient in the iStent inject® group experienced elevated IOP (48 mm Hg) and 4 required ocular hypotensive medication. Longer-term studies are in progress.
 
 
Viscocanalostomy
A 2010 meta-analysis by Chai and Loon compared the safety and efficacy of viscocanalostomy with the gold standard of trabeculectomy (Chai, 2010).Ten randomized controlled trials with a total of 458 eyes (397 patients) with medically uncontrolled glaucoma were included in the analysis. The number of eyes in each study ranged from 20 to 60, with follow-up ranging from 6 months to 4 years. The majority of eyes
(81%) had primary open angle glaucoma, while 16.4% had secondary open angle glaucoma, and 1.7% had primary angle closure glaucoma. Meta-analysis found that trabeculectomy had a significantly better pressure-lowering outcome. The difference in intraocular pressure between the treatments was 2.25 mm Hg at 6 months, 3.64 mm Hg at 12 months, and 3.42 mm Hg at 24 months. Viscocanalostomy had a significantly higher relative risk (RR) of perforation of Descemet’s membrane (RR: 7.72). In contrast, viscocanalostomy had significantly fewer postoperative events compared with trabeculectomy (hypotony RR: 0.29, hyphema RR: 0.50, shallow anterior chamber RR: 0.19, and cataract formation RR: 0.31). Although viscocanalostomy had a better risk profile, most of the adverse events associated with trabeculectomy were considered to be mild and reversible. Similar results were obtained in a 2014 Cochrane review and meta-analysis by Edaly et al that included 2 small randomized trials (50 eyes( (Eldaly, 2014).
 
 
The primary literature on canaloplasty consists mainly of case series that compare post-treatment IOP with pretreatment IOP. One retrospective comparative study evaluated outcomes from 33 eyes (33 patients) that underwent canaloplasty and 46 eyes (46 patients) that underwent trabeculectomy during a 2 year period and had a minimum of 12 months’ of follow-up (Ayyala, 2011). This study group was drawn from a larger group of 243 patients who underwent surgery during the same 2 year period (87 canaloplasty procedures and 156 trabeculectomy procedures). The specific procedure was determined by the ability to obtain insurance coverage for canaloplasty, and the groups were comparable in demographics, previous surgery, and visual acuity at baseline. At 12 months after surgery, the mean reduction in IOP from preoperative values was 32% for canaloplasty and 43% for trabeculectomy (p=.072). IOP was slightly lower in the trabeculectomy group (11.6 vs 13.8 mm Hg; p=.03) and fewer patients needed postoperative glaucoma medications. There was no significant difference in surgical reoperation rates between the 2 procedures (15% canaloplasty and 11% trabeculectomy). This study is limited by the potential for bias in the selection of patients for the study. Only a minority of all surgical patients had 12-month follow-up data and was included in the study and section into treatment groups was dependent on insurance status.
 
Three year follow-up from an independent series of 214 patients treated with canaloplasty in Europe was reported by Brusini in 2014 (Brusini. 2014). Mean IOP was reduced from 29.4 mm Hg at baseline to 17.0 mm Hg, after excluding 17 patients (7.9%) who later underwent trabeculectomy,. IOP was 21 mm Hg or lower in 86.2% of patients, 18 mm Hg or lower in 58.6%, and 16 mm Hg or lower in 37.9% of patients. There was a decrease in mean medication use, from 3.3 at baseline to 1.3 at follow-up. Complications, which included hyphema, descement membrane detachment, IOP spikes, and hypotony, were fewer than is typically seen with trabeculectomy. Several disadvantages of the procedure were noted, including the inability to complete the procedure in 16.4% of eyes.
 
Ongoing Clinical Trials
A search of the online site ClinicalTrials.gov in July 2014 found 2 randomized trials comparing canaloplasty to trabeculectomy. NCT01228799 enrolled 64 patients and was completed December 2012. No results have been posted to date.
 
NCT00854256 has an expected enrollment of 60 patients with completion in May 2014. NCT01726543 will compare canaloplasty with non-penetrating deep sclerectomy. This study has an estimated enrollment of 80 patients with completion in December 2014.
 
2016 Update
A literature search conducted through February 2016 did not reveal any new randomized controlled trials or any new information that would prompt a change in the coverage statement. The key identified literature are summarized below.
 
Ex-PRESS Mini Shunt
Two additional small RCTs were published in 2015 by Gonzalez-Rodriguez (Gonzalez-Rodriguez, 2015) et al (n=63) and Wagschal et al (Wagschal, 2015) (n=64). Both of these studies corroborated the results of the earlier RCTs, reporting that there were no differences between the trabeculectomy and Ex-PRESS shunt groups on the outcomes of mean IOP, success rates, number of medications used, or complication rates.
 
A Cochrane review was published in 2015 that evaluated the efficacy of adjunctive procedures added to trabeculectomy (Wang, 2015). The Ex-PRESS Mini Shunt was one procedure included and there were three RCTs included that compared trabeculectomy alone with trabeculectomy plus Ex-PRESS mini shunt. The three trials were rated as having high or unclear risk of bias by the Cochrane risk of bias tool. None of the three individual RCTs reported a significant improvement for the Ex-PRESS group. On combined analysis the IOP was slightly lower in the combination group compared with trabeculectomy alone (weighted mean difference -1.58, 95% CI -2.74 to -0.42). Combined analysis also showed that subsequent cataract surgery was less frequent in the combination group compared with trabeculectomy alone (Relative Risk 0.34, 95% CI 0.14-0.74). There was also a lower rate of some complications in the combination group, such as hyphema and needling, but no difference in the rate of other complications such as bleb leakage and anterior chamber flattening.
 
iStent
Four year follow-up from an earlier discussed study (Fea, 2010) was published in 2015 (Fea, 2015). A total of 24 of 36 patients were available at four years of follow-up. At this longer time point, the differences between treatment group remained non-significant, with a mean IOP of 15.9mmHg in the stent group and 17mmHg in the control group (p=NS).
One RCT comparing the efficacy of one iStent versus multiple iStents was published in 2015 (Katz, 2015). This study, from a single institution in Armenia, randomized 119 patients with OAG and an IOP between 22-38mmHg (off medications) to either one shunt (n=38), two shunts (n=41), or three shunts (n=40). Randomization was performed using a pseudorandom number generator. The main outcome measure was IOP at 12 months. The primary end point was the percent of patients with 20% reduction in IOP off medications. This endpoint was reached by 89.2% (95% CI 74.6-97.0%) of patients in the one stent group, 90.2% (95% CI 76.9-97.3%) of patients in the two stent group, and 92.1% (95% CI 78.6-98.3) of patients in the three stent group. The secondary endpoint was the percent of patients who achieved an IOP of 15 off medications. This endpoint was reached by 64.9% (95% CI 47.5-79.8%) of patients in the one stent group, 85.4% (95% CI 70.8-94.4%) of patients in the two stent group, and 92.1% (95% CI 78.6-98.3) of patients in the three stent group. There were no between group statistical comparisons reported.
 
A prospective case series enrolled 39 patients with OAG and IOP between 18 and 30mmHg (Donnenfeld, 2015). Each patient was treated with two microstents and medications as needed, and follow-up was for three years. At study completion, the mean reduction in IOP was 9.1mmHg (95% CI 8.0-10.1). There was one postoperative complication, which was a hyphema that resolved without further intervention.
 
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through May 2018. Coverage statement revised. The key identified literature is summarized below.
 
Randomized Controlled Trials
Kotecha et al assessed vision-related quality of life outcomes in the TVT study (Kotecha, 2017). Quality of life was measured using the National Eye Institute Visual Functioning Questionnaire-25, administered at baseline and annual follow-ups over 5 years. A comparison of composite quality of life scores and change in scores over time among the 2 groups revealed no significant differences at any of the follow-up measurements.
 
Observational Studies
Dib Bustros et al published a retrospective chart review that offered 1-year results from 56 African American patients who underwent Ex-PRESS (n=28) implantation or trabeculectomy (n=28)(Dib Bustros, 2017). Outcomes included IOP and glaucoma medication used presurgery, postsurgery, and at 12-months of follow-up. In both groups, IOP and glaucoma-related medication use dropped significantly. Postoperative and follow-up interventions included 5-fluorouracil injections and laser suture lysis. Patients who underwent trabeculectomy needed a significantly greater number of laser suture lysis and 5-fluorouracil interventions in the 3 months after surgery (trabeculectomy: 3.89; EX-PRESS: 2.36, p=0.007). The results showed that Ex-PRESS was noninferior to trabeculectomy in reducing IOP and reducing the need for glaucoma-related medications.
 
Comparative Effectiveness Analyses
Christakis et al analyzed 5-year pooled data from the ABC and AVB trials comparing the relative efficacy of the 2 implants (Christakis, 2017). Patients were randomized to an Ahmet implant (n=267) or a Baerveldt implant (n=247). IOP, glaucoma medication use, and visual acuity were compared. At year 5, mean IOP was 15.8 mm Hg in the Ahmed group and 13.2 mm Hg in the Baerveldt group (p=.007). The cumulative failure rate in the Ahmed group was 49%; in the Baerveldt group, it was 37%. Mean glaucoma medication use was significantly lower in patients receiving the Baerveldt implant than in patients receiving the Ahmed implant (p=0.007). Visual acuity was similar between both groups. While efficacy measures were significantly better in the Baerveldt group, these patients experienced more hypotony (4.5%) than patients in the Ahmet group (0.4%; p=.002).
 
Comparative Studies
Schlenker et al published a multicenter, retrospective interventional cohort study that compared the risk, safety, and efficacy for stand-alone ab interno microstent implantation with mitomycin C (MMC) and trabeculectomy plus MMC (Schlenker, 2017). Implantations of the ab interno XEN 45 gelatin microstent is a new less invasive surgery than trabeculectomy. This study included 293 patients (354 eyes) across 4 ophthalmology centers in Canada, Germany, Austria, and Belgium. One hundred fifty-nine patients (185 eyes) underwent the microstent implantation, and 139 patients (169 eyes) underwent trabeculectomy. Outcomes included: IOP differences, medication reductions, interventions, complications, and the need for additional surgery. The primary outcome was the hazard ratio of failure. Failure was defined as 2 consecutive IOP readings of less than 6 mm Hg, including vision loss. Success was measured by the withdrawal of glaucoma-related medications at 1 month postsurgery. The adjusted hazard ratio of failure of the microstent relative to trabeculectomy was 1.2 for complete success (95% CI, 0.7 to 2.0). Both surgeries had a 75% survival of approximately 10 months for complete success. During the last reported follow-up (varying times), antiglaucoma medications were being used by 25% of patients who received the microstent implantation and 33% of trabeculectomy patients. Patients in both groups reported similar numbers of postoperative interventions, such as laser suture lysis and needling. The need for reoperation was higher among those who had undergone microstent implantation—but this difference was not statistically significant. The authors concluded that the ab interno gelatin microstent with MMC was noninferior to trabeculectomy plus MMC.
 
Noncomparative Studies
Mansouri et al reported on results from a study of 149 eyes (113 patients); 109 eyes received the XEN implant pluscataract surgery and 40 eyes received the implant alone (Mansouri, 2017).\l " There was a range of glaucoma severity represented in the study sample, with most patients in the mild-to-moderate stages. Of the 149 eyes, data for 87 (58%) eyes was available at 12 months. The high loss to follow-up was mainly due to high travel times for patients referred to the study treatment center from various provinces and countries, and to lack of interest among physicians to treat referred patients. At 12 months, mean IOP and mean medication use both decreased.  The proportion achieving 20% or more reduction in IOP was higher among patients receiving XEN alone than those undergoing cataract surgery and XEN implantation. Adverse events included bleb revision (n=5), choroidal detachment (n=2), and second glaucoma surgery (n=9).
 
Grover et al published results from the single-arm, open-label clinical study evaluating the effectiveness and safety of the XEN Glaucoma Treatment System in 65 patients with refractory glaucoma (Grover, 2017). Effectiveness data were collected for 12 months and safety data for 18 months. The mean diurnal IOP was 25 mm Hg at baseline on a mean of 3.5 IOP-lowering medications. Forty-six (75%) patients of 61 with available data had a 12-month mean diurnal IOP reduction of 20% or more without increasing IOP-lowering medications. The mean IOP reduction at 12 months was -9.1 mm Hg (95% CI, -10.7 to -7.5 mm Hg) on a mean of 1.7 medications. Efficacy was consistent across age groups, baseline IOP, baseline medication use, sex, and ethnicity. The most common adverse events were glaucoma surgery, hypotony, IOP increase of 10 mm Hg or more, and needling procedures. FDA cited results from this study to conclude that the XEN System was as safe and effective as predicate devices.
 
Hengerer et al retrospectively analyzed 146 patients (242 eyes) receiving the XEN implant for treatment refractory to antiglaucoma medication or glaucoma surgery (Hengerer, 2017). In the subset of eyes with 12-month data (n=148), IOP reduction of 20% or more was achieved by 73.0% of patients. Mean antiglaucoma medications decreased. The decreases in IOP and medication use were statistically significant, in patients receiving the XEN implant alone and in patients receiving the XEN implant while undergoing cataract surgery.
 
Five smaller case series have also assessed the use of the XEN. These case series reported significant reductions in IOP and medication use (Perez-Torregrosa, 2016; De Gregorio, 2017; Galal, 2017; Ozal, 2017; Tan, 2018). Low rates of the following complications were reported: hypotony (which resolved), need for bleb intervention, iris tissue obstruction, implant extrusion, and choroidal detachment.
 
Observational Studies
Kurji et al reported on 2 surgical methods, phaco-trabectome and phaco-iStent, to control IOP in patients with open-angle glaucoma undergoing cataract surgery (Kurji, 2017). Fifty-five patients (70 eyes) were analyzed in this retrospective comparative case series, 36 receiving PT and 34 receiving phaco-iStent. Outcomes included IOP reduction, glaucoma medication reduction, patients’ safety profile, and best-corrected visual acuity. At baseline, the mean IOP of patients in the phaco-trabectome group (30 patients [36 eyes], 20.92 mm Hg]) was higher than those in the phaco-iStent group (25 patients [34 eyes], 17.47 mm Hg; p=0.026]). At 12-month follow-up, both groups experienced significant reductions in IOP; however, there was no statistically significant difference between groups (phaco-trabectome, -5.09 mm Hg 24% relative reduction vs phaco-iStent, -3.84 mm Hg, 22% relative reduction; p=0.331). Glaucoma medication usage did not decrease significantly from baseline to 12 months in either group; moreover, there was no significant difference in reduction between the groups. Phaco-iStent patients had fewer individual complications.
 
Ferguson et al reported on a series of 59 patients with severe primary open-angle glaucoma who were implanted with 1 trabecular micro-bypass stent (iStent) during cataract surgery (Ferguson, 2018). Patients were followed for 2 years. IOP at baseline was 19.3 mm Hg at baseline, decreasing significantly to 14.4 mm Hg at 12 months and 14.9 mm Hg at 24 months (p<0.01). Mean number of glaucoma medications also decreased, from 2.3 at baseline to 1.6 at 24 months.
 
Multiple Stents
An RCT comparing the efficacy of 1 iStent with multiple iStent devices was published by Katz et al (Katz, 2015). This trial, from a single institution in Armenia, randomized 119 patients with mild-to-moderate open-angle glaucoma and an IOP between 22 and 38 mm Hg (off medications) to 1 stent (n=38), 2 stents (n=41), or 3 stents (n=40). Randomization was performed using a pseudorandom number generator. The main outcome was IOP at 12 months. The primary end point was the percentage of patients with a reduction of 20% or more in IOP off medications. This end point was reached by 89.2% (95% CI, 74.6% to 97.0%) of the 1-stent group, by 90.2% (95% CI, 76.9% to 97.3%) of the 2-stent group, and by 92.1% (95% CI, 78.6% to 98.3%) of the 3-stent group. The secondary end point (percentage of patients achieving an IOP £15 mm Hg off medication) was reached by 64.9% (95% CI, 47.5% to 79.8%) of the 1-stent group, by 85.4% (95% CI, 70.8% to 94.4%) of the 2-stent group, and by 92.1% (95% CI, 78.6% to 98.3) of the 3-stent group. Forty-two-month follow-up results for 109 patients were published by Katz et al (Katz, 2018). Mean medicated IOPs for the 1-stent, 2-stent, and 3-stent groups were 15.0 ± 2.8 mm Hg, 15.7 ± 1.0 mm Hg, and 14.8 ± 1.3 mm Hg, respectively. No between-group statistical comparisons were reported.
 
Vlasov et al conducted a retrospective chart review of patients with open-angle glaucoma receiving either 1 iStent (n=39) or 2 iStents (n=30) during cataract surgery (Vlasov, 2017). Both groups experienced statistically significant reductions in IOP, and there was no significant difference between them in IOP reduction. Only the group receiving 2 iStents experienced a statistically significant reduction in medication use.
 
Practice Guidelines and Position Statements
 
European Glaucoma Society
The European Glaucoma Society’s Terminology and Guidelines for Glaucoma (2014) provided evidence-based guidelines on the treatment of primary open-angle glaucoma (European Glaucoma Society, 2014). The guidelines were updated in 2017 (European Glaucoma Society, 2017). The guidelines stated that there are no well-controlled comparative trials to support the superiority in safety or efficacy of MIGS, including both ab interno and ab externo procedures, over trabeculectomy.    
 
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2019. The key identified literature is summarized below.
 
Omatsu et al compared changes in corneal endothelial cells among patients undergoing trabeculectomy (n=60) and patients receiving EX-PRESS shunts (n=50) (Omatsu, 2018). Both groups experienced significant decreases in IOP compared with baseline. After two years of follow-up, patients undergoing trabeculectomy experienced significant decreases in corneal endothelial cells compared with baseline, while the EX-PRESS group did not.
 
A small RCT by Bo et al randomizing 68 patients compared the EX-PRESS shunt (n=33) and the Ahmed shunt (n=35) (Bo, 2018). Follow-up at nine months showed no difference in best-corrected visual acuity or in postoperative complications. Control of IOP was superior in EX-PRESS compared with the Ahmed shunt.
 
2020 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2019. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
One non-randomized comparative study was reported by Hooshmand et al on outcomes with the use of the iStent inject, which simultaneously injects 2 stents through a single ab interno opening, compared to the first generation single iStent (Hooshmand, 2019). The iStent inject was developed to provide easier ab interno insertion and comes preloaded with 2 stents that are smaller than the first-generation iStent. There was no significant difference between the earlier model and the second generation device on outcomes at 12 months, but Kaplan-Meier analysis found an earlier time to add topical medications in the iStent inject patients. Limitations of the study include the length of follow-up, which was limited by the time that the iStent inject had been available, and the non-randomized design. In addition, the study compared two cohorts from different time periods, those who had been treated with the first generation device and those who had been treated with the second-generation device. Efficacy of the iStent inject at longer follow-up is unknown.
 
 
The Cochrane review by Le et al on the iStent in patients with open-angle glaucoma identified 2 RCTs that compared treatment with iStent or iStent inject to medical therapy, and 1 RCT that compared 1, 2, or 3 iStents (Le, 2019). Meta-analysis was not performed due to heterogeneity. However, in both trials, iStent implantation resulted in a higher proportion of patients who were drop free and reduced the mean number of drops when compared to medical therapy. One RCT indicated that compared to implantation of 1onestent, implantation of 2 or 3 stents resulted in a similar proportion of patients who were drop free at 36 months or less, but a higher proportion of patients who were drop free after 36 months.
 
 
Samuelson et al, reported on the pivotal trial on the iStent inject (Samuelson, 2019). A total of 505 patients undergoing cataract surgery were randomized after lens implantation to insertion of 2 smaller iStents or control. Results were assessed by intention-to-treat analysis and per-protocol analysis, with patients requiring additional surgical procedures considered to be failures. The addition of medications was based on a standardized protocol. At the 2-year follow-up, a greater percentage of patients had achieved at least a 20% reduction in IOP (75.8% vs 61.9%, p=0.005), had a greater reduction inIOP (7.0 vs 5.4, p<0.001), and required fewer topical medications (0.4 vs 0.8, p<0.001).
 
iStent was compared with the Hydrus microstent in a double-blind multicenter RCT by Ahmed et al (Ahmed, 2019). Eyes (n=152) with mild-to-moderate glaucoma and an IOP of 23 to 39 after washout of medication were randomized to either 1 Hydrus stent or 2 iStents as a stand-alone treatment. Both stents have FDA approval in the U.S. when used in conjunction with cataract surgery, but not as a stand-alone procedure. Follow-up was performed through 12 months post-operatively with medications added at the investigator's discretion. The Hydrus outperformed 2 iStents in nearly every measure. Eyes implanted with the Hydrus microstent were able to maintain IOP < 18 mm Hg on fewer medications and a greater percentage of patients were medication-free compared to the iStent group (46.6% vs 24.0%, p<0.001). The decision to increase medications was up to the investigator and not pre-specified, but post-hoc analysis indicated that the IOP at which medications were increased was similar in the two groups.
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2020. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
A Cochrane review by Otarola et al included 3 studies with 808 participants (Otarola, 2020). Two studies were conducted in patients with cataracts and OAG (n=653), and compared the Hydrus microsent combined with cataract surgery to cataract surgery alone (Pfeiffer, 2015; Samuelson, 2019). They found moderate-certainty evidence that adding the Hydrus microstent to cataract surgery in patients with mild or moderate OAG increased the proportion of participants who were medication-free at 12 month (risk ratio 1.59, 95% confidence interval 1.39 to 1.83) and 24 month follow-up (risk ratio 1.63, 95% confidence interval 1.40 to 1.888), and reduced unmedicated IOP by 2 mm Hg, the number of medications by -0.41, and the need for secondary glaucoma surgery.
 
Four-year follow-up of iStent inject is reported in 2 phase 4 publications from the MIGS study group (Berdahl, 2020; Lindstrom, 2020). Berdahl et al reported on 53 patients who were on 2 preoperative medications who received 2 iStent inject implants and started on travoprost on postoperative Day 1. At 48-month follow-up, 85% of eyes had reduced IOP (> 20%) with a single medication as compared to the baseline IOP on 2 medications. Mean IOP on 1 medication was 11.9 to 13.0 mm Hg, compared to 19.7 on 2 medications preoperatively. Lindstrom et al reported on 57 patients who were on 1 preoperative medication before implantation of 2 iStent inject devices. Month 48 IOP without medication was reduced (> 20%) in 95% of eyes with iStent inject. There were no adverse events that were considered to be related to the devices.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2021. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Subsequent publications of randomized controlled trials have reported no significant differences between the groups for vision-related quality of life or visual field outcomes from the Tube vs Trabeculectomy study (Kotecha, 2017; Swaminathan, 2020).
 
A U.S. multicenter randomized trial by Netland et al, compared trabeculectomy with EX-PRESS implantation in 120 patients (120 eyes) (Netland, 2014). Comparator groups were similar at baseline. Throughout a 2 year postsurgical follow-up, average IOP and number of medications were similar between groups. Surgical success was 90% and 87% at 1 year and 83% and 79% at 3 years in the EX-PRESS and trabeculectomy groups, respectively. Visual acuity returned to near baseline levels at 1 month after EX-PRESS implantation (median, 0.7 months) and at 3 months after trabeculectomy (median, 2.2 months; p =.041). Postoperative complications were higher after trabeculectomy (41%) than after EX-PRESS implantation (18.6%).
 
Additional single-center RCTs have corroborated the results of the multicenter trial (de Jong, 2009; de Jong, 2011; Wagschal, 2015; Gonzalez-Rodriguez, 2016; Konopinska, 2021).
 
Wagner et al also reported similar success rates for trabeculectomy (65.5%, 95% CI, 55.6 to 75.9%) and XEN Implant (58.5%, 95% CI, 47.6 to 69.4%, p =.16; adjusted odds ratio 0.66, 95% CI, 0.32 to 1.37) but a greater reduction in IOP with trabeculectomy (10.5 mm Hg) compared to the XEN implant (7.2 mm Hg; p =.003) (Wagner, 2020). Baseline measurements showed older age (73.0 vs 67.2) and a lower number of medication classes (2.0 vs 3.0) for the XEN group. A regression mixed model that adjusted for gender, age, preoperative IOP, and medications did not indicate a difference in the proportion of success for the 2 groups.
 
Stoner et al conducted a retrospective comparative study of 100 eyes that had undergone either XEN or EX-PRESS standalone shunt implantation at a single center (Stoner, 2021). Surgical success was defined as IOP between 6 and 18 mm Hg without reoperation, loss of light perception, device removal, or use of glaucoma medications. The incidence of adverse effects during the first 3 months was lower with the XEN implant, but the failure rate at 1 year was higher (HR 3.94, 95% CI, 1.73 to 9.00, p =.001) compared to EX-PRESS. Sensitivity analysis to adjust for differences in baseline characteristics between the groups in this retrospective study achieved similar results.
 
The largest study with a follow-up of longer than 1 year was by Gabbay et al, who reported a retrospective analysis of 205 patients/eyes that had received an XEN implant (Gabbay, 2021). At 3 years, 25% of eyes met the criteria for success, with a failure rate of 25% and requirement for needling in 36.6%. For eyes that retained an XEN implant, IOP decreased from an average of 22.6 mmHg (standard deviation [SD], 7.0) before surgery to 14.0 (SD, 2.9) at 3 years; the number of medications decreased from an average of 2.6 (SD, 1.1) to 0.6 (SD, 1.0) at 3 years. The failure rate was higher in non-Caucasians (74% of 13) compared to Caucasians (21% of 188, p <.001), with Caucasians comprising 93.5% of the study population.
 
An industry-sponsored meta-analysis of standalone iStents was reported by Healey et al (Healey, 2021). The investigators included 4 RCTs and 9 non-randomized or single-arm studies with at least 6 months of follow-up. The number of eyes in the studies ranged from 15 to 99 (total N=778). The pooled weighted reduction in IOP was reported as 31.1% at 6 to 12 months and 32.9% at 60 months with a reduction of approximately 1 medication in the pooled analysis. In the individual studies, the reduction in IOP ranged from -1.0 to -10.7; the largest reduction in IOP was in a prospective case series (n=44) with 25% loss to follow-up. The lowest reduction in IOP (-1.0) was in a larger RCT (n=77) with low loss to follow-up (2.5%). Notably, the systematic review did not report the number of device failures in these studies. Additional limitations are the inclusion of retrospective case series and the high heterogeneity between studies, which would typically preclude meta-analysis.
 
Al Yousef et al conducted a matched comparison of the iStent inject and ab interno trabeculectomy in 78 eyes (Al Yousef, 2020). IOP was reduced in both groups at 1-month follow-up but began to rise at 12 months in the iStent inject group. By 24 months, the IOP in the iStent inject group had returned to near preoperative levels. The IOP in the Trabectome group was lower than the iStent inject group throughout follow-up.
 
Efficacy of the iStent inject at 3-year follow-up was reported by Salimi et al in a consecutive case series of 124 eyes with different glaucoma subtypes and severities (Salimi, 2021). Mean IOP in patients who retained an implant was reduced from 16.9 mm Hg preoperatively to 13.17 mm Hg (p <.001) with a reduction in medications from 2.38 to 1.16 (p <.001). The 3-year survival rate of the implant was only 74%.
 
In 2020, the American Glaucoma Society published a position paper on microinvasive glaucoma surgery (Fellman, 2020). The Society supports efforts that facilitate patient access to these procedures, including more flexible regulatory pathways for new devices, expansion of the indications for already approved devices, and greater availability of information obtained by regulatory authorities.
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2022. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Zhang et al compared the effectiveness of trabeculectomy and Ahmed and EX-PRESS implants in the treatment of primary and secondary glaucoma via a systematic review and network meta-analysis (Zhang, 2022). The review included 14 RCTs, involving 866 eyes of 808 patients. Overall, there were 339 eyes in the trabeculectomy group, 368 eyes in the EX-PRESS group, and 159 eyes in the Ahmed group. Results revealed that after 3 months, trabeculectomy was associated with similar improvement in IOP as compared to Ahmed (weighted mean difference [WMD], 0.014; 95% confidence interval [CI], -0.14 to 0.18) and EX-PRESS (WMD, 0.014; 95% CI, -0.072 to 0.097). However, at 1 year, EX-PRESS was associated with a significant improvement in IOP (WMD, 0.097; 95% CI, 0.008 to 0.18) as well as complete success (relative risk [RR], 0.73; 95% CI, 0.57 to 0.93) as compared to trabeculectomy. In a comparison of EX-PRESS and Ahmed implants, EX-PRESS was found to be superior to Ahmed with regard to reduction in the number of post-operative medications. Limitations of this meta-analysis included the presence of publication bias and heterogeneity of the included data.
 
Lim et al conducted a systematic review and meta-analysis of 14 studies (N=963 eyes) involving the stand alone XEN45 gel stent ab interno device implant (Lim, 2022). The review included 7 prospective and 7 retrospective studies. The mean age of included patients was 66 years and the maximum follow-up duration ranged from 6 to 30 months. A variety of surgical techniques were employed across the studies; however, surgical steps were largely consistent. Results revealed that implantation of the XEN45 gel stent significantly decreased IOP (p<.001) across all timepoints (1 day, 1 week, 1, 3, 6, 12, 18, and 24 months) with a mean decrease of 7.44 mmHg at 24 months. The use of IOP-lowering medications was also reduced significantly (p<.001) post-implantation across all timepoints (1 week, 1, 3, 6, 12, 18, and 24 months) with a mean reduction of 1.67 medications at 24 months. Serious adverse events occurred rarely with transient numerical hypotony the most common postoperative complication. Postoperative needling procedures were required in 38% of eyes during the entire follow-up period. The overall quality of the evidence within the systematic review was low, with most included studies being case series with relatively short follow-up durations and a lack of standardized definitions of treatment success and failure. Additional RCTs with a clinically meaningful definition of success and failure are needed.
 
Another systematic review and meta-analysis that evaluated the efficacy of the XEN gel stent implant in 78 eligible studies reported similar conclusions (Yang, 2022). Following XEN stent implantation, there was a significant reduction in IOP (p<.001) and the number of anti-glaucoma medications used (p<.001) through 48 months post-surgery. However, the quality of included studies was noted to be relatively low and the definition of outcomes was inconsistent across the included studies.
 
In 2020, the AAO updated its preferred practice pattern on primary open-angle glaucoma (POAG) (Gedde, 2020). The document notes that aqueous shunts have traditionally been used to manage medically uncontrolled glaucoma when trabeculectomy has failed to control IOP or is deemed unlikely to succeed; however, the indications for using aqueous shunts have been broadening, and these devices are being increasingly used in the surgical management of glaucoma. The preferred practice pattern notes that "several studies have compared aqueous shunts with trabeculectomy" and that the "selection of aqueous shunts or trabeculectomy should be left to the discretion of the treating ophthalmologist, in consultation with the individual patient."

CPT/HCPCS:
0191TInsertion of anterior segment aqueous drainage device, without extraocular reservoir, internal approach, into the trabecular meshwork; initial insertion
0253TInsertion of anterior segment aqueous drainage device, without extraocular reservoir, internal approach, into the suprachoroidal space
0356TInsertion of drug eluting implant (including punctal dilation and implant removal when performed) into lacrimal canaliculus, each
0376TInsertion of anterior segment aqueous drainage device, without extraocular reservoir, internal approach, into the trabecular meshwork; each additional device insertion (List separately in addition to code for primary procedure)
0444TInitial placement of a drug eluting ocular insert under one or more eyelids, including fitting, training, and insertion, unilateral or bilateral
0445TSubsequent placement of a drug eluting ocular insert under one or more eyelids, including re training, and removal of existing insert, unilateral or bilateral
0449TInsertion of aqueous drainage device, without extraocular reservoir, internal approach, into the subconjunctival space; initial device
0450TInsertion of aqueous drainage device, without extraocular reservoir, internal approach, into the subconjunctival space; each additional device (List separately in addition to code for primary procedure)
0474TInsertion of anterior segment aqueous drainage device, with creation of intraocular reservoir, internal approach, into the supraciliary space
0671TInsertion of anterior segment aqueous drainage device into the trabecular meshwork, without external reservoir, and without concomitant cataract removal, one or more
66179Aqueous shunt to extraocular equatorial plate reservoir, external approach; without graft
66180Aqueous shunt to extraocular equatorial plate reservoir, external approach; with graft
66183Insertion of anterior segment aqueous drainage device, without extraocular reservoir, external approach
66184Revision of aqueous shunt to extraocular equatorial plate reservoir; without graft
66989Extracapsular cataract removal with insertion of intraocular lens prosthesis (1 stage procedure), manual or mechanical technique (eg, irrigation and aspiration or phacoemulsification), complex, requiring devices or techniques not generally used in routine
66991Extracapsular cataract removal with insertion of intraocular lens prosthesis (1 stage procedure), manual or mechanical technique (eg, irrigation and aspiration or phacoemulsification); with insertion of intraocular (eg, trabecular meshwork, supraciliary,
L8612Aqueous shunt

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