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 (e.g., trabeculectomy), alternative surgical treatments (e.g., transluminal dilation by viscocanalostomy or canaloplasty) are being evaluated for patients with glaucoma. 

For individuals who have open-angle glaucoma who have failed medical therapy who receive viscocanalostomy, the evidence includes small randomized controlled trials (RCTs) comparing viscocanalostomy with trabeculectomy. Relevant outcomes are symptoms, morbid events, quality of life, and medication use. Meta-analysis of these trials has indicated that trabeculectomy has a greater IOP-lowering effect than viscocanalostomy. Reduction in IOP was greater with canaloplasty than viscocanalostomy in a small within-subject comparison. Viscocanalostomy has not been shown to be as good as or better than established alternatives. The evidence is sufficient to determine that the technology is unlikely to improve the net health outcome.  

For individuals who have open-angle glaucoma who have failed medical therapy who receive canaloplasty, the evidence includes 1 RCT, 1 comparative effectiveness review, and several case series. Relevant outcomes are symptoms, morbid events, quality of life, and medication use. The RCT found not only significantly higher complete success rates with trabeculectomy than with canaloplasty, but also higher complication rates. The qualified success rate (with medication) was similar between groups. A systematic review found that canaloplasty provided modest IOP reduction (to 16 mm Hg) with minor intraoperative or postoperative complications. Further evidence from RCTs is required to corroborate results of this single trial. The evidence is insufficient to determine the effects of the technology on health outcomes.  

Clinical input in 2011 considered canaloplasty to be appropriate for a select group of patients, including those who are at risk for infection or hypotony, who have surface disease precluding the creation of good trabeculectomy bleb, or who would not be able to cover a glaucoma drainage device implant. In this clinical context, the evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Background  
Impaired Aqueous Humor Drainage
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 Schlemm canal can disrupt the balance of aqueous humor inflow and outflow, resulting in an increase in intraocular pressure and glaucoma risk.

Treatment
Surgical intervention may be indicated in patients with glaucoma when the target intraocular pressure cannot be reached pharmacologically. Trabeculectomy (guarded filtration surgery) is the most established surgical procedure for glaucoma, allowing aqueous humor to directly enter the subconjunctival space. This procedure creates a subconjunctival reservoir with a filtering “bleb” on the eye, which can effectively reduce intraocular pressure, but is associated with numerous and sometimes sight-threatening complications (e.g., leaks, hypotony, choroidal effusions and hemorrhages, hyphemas or bleb-related endophthalmitis) and long-term failure. Other surgical procedures (not addressed herein) include trabecular laser ablation and deep sclerectomy, which removes the outer wall of Schlemm canal and excises deep sclera and peripheral cornea.

More recently, the Trabectome™, an electrocautery device with irrigation and aspiration, has been used to selectively ablate the trabecular meshwork and inner wall of Schlemm canal without external access or creation of a subconjunctival bleb. Intraocular pressure with this ab interno procedure is typically higher than the pressure achieved with standard filtering trabeculectomy. Aqueous shunts may also be placed to facilitate drainage of aqueous humor (see evidence review 9.03.21). Complications from anterior chamber shunts include corneal endothelial failure and erosion of the overlying conjunctiva.

Alternative nonpenetrating methods being evaluated to treat glaucoma are viscocanalostomy and canaloplasty. Viscocanalostomy is a variant of deep sclerectomy and unroofs and dilates the Schlemm canal without penetrating the trabecular meshwork or anterior chamber. A high-viscosity viscoelastic solution (e.g., sodium hyaluronate) is used to open the canal and create a passage from the canal to a scleral reservoir. It has been proposed that viscocanalostomy may lower intraocular pressure while avoiding bleb-related complications.

Canaloplasty, which evolved from viscocanalostomy, involves dilation and tension of the Schlemm canal with a suture loop between the inner wall of the canal and the trabecular meshwork. This ab externo procedure uses the iTrack illuminated microcatheter to access and dilate the length of the Schlemm canal and to pass the suture loop through the canal. An important difference between viscocanalostomy and canaloplasty is that canaloplasty attempts to open the entire length of the Schlemm canal, rather than one section.

Because aqueous humor outflow is pressure-dependent, the pressure in the reservoir and venous system is critical for reaching the target intraocular pressure. Therefore, some procedures may not reduce intraocular pressure below the pressure of the distal outflow system used (e.g., < 15 mm Hg), and are not indicated for patients for whom very low intraocular pressure is desired (e.g., those with advanced glaucoma).

Regulatory Status
In 2004, iTrack™ (iScience Interventional) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process as a surgical ophthalmic microcannula that is indicated for the general purpose of "fluid infusion and aspiration, as well as illumination, during surgery." In 2008, iTrack™ was cleared by FDA for "catheterization and viscodilation of [the] Schlemm canal to reduce intraocular pressure in adult patients with open angle glaucoma." FDA product code: MPA. 

Related Policies
90306 Ophthalmologic Techniques for Evaluating Glaucoma
90321 Aqueous Shunts and Stents for Glaucoma

Policy
Canaloplasty may be considered MEDICALLY NECESSARY 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.
• 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 is investigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY under all other conditions, including angle-closure glaucoma.

Viscocanalostomy is considered NOT MEDICALLY NECESSARY.   

Policy Guidelines
Tensioning devices are only able to reduce IOP to the mid-teens and may be inadequate when very low IOP is needed to reduce glaucoma damage.

The CPT codes for these procedures are as follows:

66174 — Transluminal dilation of aqueous outflow canal; without retention of device or stent
66175 — Transluminal dilation of aqueous outflow canal; with retention of device or stent

The insertion of the iTrack device for subchoroidal delivery of pharmacologic agents is addressed in Policy No. 90319.

Benefit Application
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all devices, drugs, or biologics approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational, and thus these devices may be assessed only on the basis of their medical necessity.

Rationale
Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function, including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, two domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice. The following is a summary of the key literature to date.

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Viscocanalostomy
Clinical Context and Therapy Purpose
The purpose of viscocanalostomy for patients who have open-angle glaucoma that has failed medical therapy is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of viscocanalostomy for patients who have open-angle glaucoma that has failed medical therapy improve net health outcomes?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is patients with open-angle glaucoma that have failed medical therapy.

Interventions
The treatment being considered is viscocanalostomy.

Comparators
The comparators of interest are intraocular pressure-lowering procedures such as glaucoma drainage implant or trabeculectomy.

Outcomes
The general outcomes of interest are symptoms, morbid events, quality of life, and medication use. Other health outcomes of interest are the intraocular pressure achieved, ability to convert to trabeculectomy if procedure is unsuccessful, and durability of procedure.

Follow-up of 15 years or longer is desirable to assess outcomes and duration of results.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
• To assess longer-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

Review of Evidence
Systematic Reviews
A meta-analysis by Chai and Loon (2010) compared the safety and efficacy of viscocanalostomy with the criterion standard of trabeculectomy.² Ten RCTs with a total of 458 eyes (397 patients) with medically uncontrolled glaucoma were analyzed. The number of eyes in each study ranged from 20 to 60, with follow-up ranging from 6 months to 4 years. Most 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 viscocanalostomy and trabeculectomy 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 the Descemet membrane (RR = 7.72). In contrast, viscocanalostomy had significantly fewer postoperative events than trabeculectomy (hypotony RR = 0.29, hyphema RR = 0.50, shallow anterior chamber RR = 0.19, cataract formation RR = 0.31). Although viscocanalostomy had a better risk profile, most adverse events associated with trabeculectomy were considered to be mild and reversible. Similar results were obtained in a Cochrane review and meta-analysis by Eldaly et al. (2014) that included 2 small randomized trials (total 50 eyes).³

Randomized Controlled Trials
A study included in the Chai and Loon systematic review is the RCT by Gilmour et al. (2009), which reported 4-year follow-up.⁴ Patients (N = 43) with open-angle glaucoma were randomized to viscocanalostomy (25 eyes) or trabeculectomy (25 eyes) and prospectively followed at regular intervals for up to 60 months. A successful outcome was defined as an intraocular pressure less than 18 mm Hg with no medications; a qualified success was defined as an intraocular pressure less than 18 mm Hg with or without topical treatment. One patient in each group was lost to follow-up. At baseline, patients had a mean intraocular pressure of 25 mm Hg and were using an average of 1.4 medications. At mean follow-up of 40 months (range, 6 – 60 months), 10 (42%) patients in the trabeculectomy group had achieved success compared with 5 (21%) patients in the viscocanalostomy group. Although 19 (79%) patients in both groups achieved qualified success, fewer trabeculectomy patients required additional topical treatment (50% vs. 83%, respectively) to achieve qualified success. There were more early postoperative complications in the trabeculectomy group (e.g., hypotony, wound leak, choroidal detachment), but they did not affect outcomes. At 1 month, conjunctival blebs were observed in 19 (79%) of the trabeculectomy group and 16 (64%) of the viscocanalostomy group. At 12 months, blebs were observed in 19 (79%) of the trabeculectomy group and 14 (56%) of the viscocanalostomy group. The proportion of patients with conjunctival blebs at final follow-up and the statistical significance of these differences were not reported. It was reported that more bleb manipulations (7 vs. 1) and antimetabolites (5 vs. 1) were needed in the trabeculectomy group. The 3 patients who required cataract surgery were in the viscocanalostomy group.

Case Series
Kobayashi et al. (2003) reported on a within-subject safety and efficacy comparison of trabeculectomy (with mitomycin C) and viscocanalostomy in 25 patients with bilateral primary open-angle glaucoma who had intraocular pressure greater than 22 mm Hg under medical therapy.⁵ Patients were randomized to trabeculectomy in 1 eye and viscocanalostomy (with removal of the internal wall of the Schlemm canal) in the other. Follow-up was performed on certain days, weeks, and months up to 12 months after surgery. Throughout follow-up, mean intraocular pressure decreased significantly more in trabeculectomy-treated eyes (e.g., from 24.8 to 12.6 mm Hg at 12 months) than in viscocanalostomy-treated eyes (from 25.0 to 17.1 mm Hg at 12 months). At 12 months, significantly more trabeculectomy-treated eyes achieved an intraocular pressure less than 20 mm Hg without medication (88% vs. 64%, respectively). Mean intraocular pressure reduction was 48.9% in trabeculectomy-treated eyes and 30.5% in viscocanalostomy-treated eyes. Overall success (intraocular pressure < 20 mm Hg) and intraocular pressure reduction greater than 30% with or without glaucoma medication did not differ significantly between the groups (96% for trabeculectomy vs. 92% for viscocanalostomy). Although trabeculectomy had a greater intraocular pressure-lowering effect, viscocanalostomy had fewer complications (1 microperforation of the Descemet membrane vs 4 cases of shallow anterior chamber, and 5 cases of hypotony with intraocular pressure < 4 mm Hg).

Grieshaber et al. (2015) reported on long-term results of viscocanalostomy for a series of 726 patients.⁶ Mean intraocular pressure before surgery was 42.6 mm Hg. Mean intraocular pressure postsurgery was 15.4 mm Hg at 5 years, 15.5 mm Hg at 10 years, and 16.8 mm Hg at 15 years. Qualified success (with or without medications) at 10 years (£ 18 mm Hg) was 40% in the European population and 59% in the African population. Laser goniopuncture was performed postoperatively on 127 (17.7%) eyes. Fifty-three (7.3%) eyes were considered failures and required reoperation. There were no significant complications.

Stangos et al. (2012) reported on the effect of the learning curve on surgical outcomes from viscocanalostomy for a retrospective series of 180 consecutive cases performed by 2 surgeons at a single center in Europe.⁷ Overall success (no visual field deterioration with an intraocular pressure ≤ 20 mm Hg) and intraocular pressure reduction of 30% or more compared with baseline values improved from 64% for the first 45 and to 91% for the last 45 cases of the series. Complete success (no medications required) improved from 38% to 73%. Surgical complications did not differ significantly between the first (16) and last 45 cases (10).

Section Summary: Viscocanalostomy
Two meta-analyses and a systematic review have evaluated RCTs comparing viscocanalostomy with trabeculectomy and reported that trabeculectomy was significantly better than viscocanalostomy at lowering intraocular pressure in patients with open-angle glaucoma. Similarly, a randomized, within-subject comparative trial reported that trabeculectomy was significantly better than viscocanalostomy at lowering intraocular pressure. However, results of other outcome measures did not differ significantly between trabeculectomy and viscocanalostomy. Viscocanalostomy was associated with fewer complications than trabeculectomy. A nonrandomized uncontrolled study suggested that results of viscocanalostomy were sustained over the long term (up to 15 years) with no significant complications. However, about 7% of treated eyes required reoperation.

Canaloplasty
Clinical Context and Therapy Purpose
The purpose of canaloplasty for patients who have open-angle glaucoma that has failed medical therapy is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of canaloplasty for patients who have open-angle glaucoma that has failed medical therapy improve net health outcomes?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is patients with open-angle glaucoma that has failed medical therapy.

Interventions
The treatment being considered is canaloplasty.

Comparators
The comparators of interest are intraocular pressure-lowering procedures such as glaucoma drainage implant or trabeculectomy.

Outcomes
The general outcomes of interest are symptoms, morbid events, quality of life, and medication use. Other health outcomes of interest are the intraocular pressure achieved, ability to convert to trabeculectomy if procedure is unsuccessful, and durability of procedure.

Follow-up of 5 years was reported in the available studies, but to assess outcomes and duration of results, longer follow-up is needed.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:.

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
• To assess longer-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

Review of Evidence
Systematic Reviews
A comparative effectiveness review of newer (Trabectome and canaloplasty) and older (trabeculectomy and Baerveldt shunt) surgeries for glaucoma was published in 2009.⁸ Twelve-month outcomes (intraocular pressure adjunctive medications, complications) were compared after glaucoma-only and combined glaucoma-phacoemulsification surgeries. Reviewers found that Trabectome and canaloplasty provided modest intraocular pressure reduction (to » 16 mm Hg) with minor intraoperative or postoperative complications. Reductions for Baerveldt glaucoma implant intraocular pressure were comparable to those for trabeculectomy (» 12 mm Hg), but the Baerveldt shunt required more postoperative intraocular pressure lowering medication (average, 1.3 medications vs. 0.5 medications, respectively) to produce a success rate comparable to trabeculectomy. Patients treated with Trabectome required more medications (average, 1.5) to control intraocular pressure than patients treated with canaloplasty (average, 0.6). Reviewers concluded that Trabectome and canaloplasty were reasonable surgical choices for patients in whom intraocular pressures in the mid-teens seemed adequate; although trabeculectomy was the most effective intraocular pressure lowering procedure, it also had the most serious complication rates.

Randomized Controlled Trials
Matlach et al. (2015) reported on an RCT with 62 patients that compared canaloplasty (n = 31) with trabeculectomy (n = 31) for the treatment of open-angle glaucoma.⁹ Patients included had medically uncontrolled or not sufficiently lowered intraocular pressure and progression of visual field defects or structural changes to the optic disc over time. The primary end point was an intraocular pressure of 18 mm Hg or less or an intraocular pressure reduction of at least 20% and less than 21 mm Hg without medication. Complete success at 2 years was achieved in 74.2% of patients after trabeculectomy and 39.1% of patients after canaloplasty (p = 0.01). The qualified success rate (with medication) did not differ significantly between the 2 groups, although more patients in the canaloplasty group needed intraocular pressure lowering medication (52.2% vs. 25.8%, respectively). Mean absolute intraocular pressure reduction was similar for both interventions. There was a trend (p = 0.08) for visual acuity to be lower in the canaloplasty group during follow-up. Trabeculectomy was associated with more frequent postoperative complications, including hypotony (37.5%), choroidal detachment (12.5%), and corneal erosion (43.8%). Scarring of the filtering bleb was a late complication in 25% of trabeculectomy patients. One study flaw was the unequal rate of dropouts (23.3% [7/30] for canaloplasty vs 3.1% [1/32] for trabeculectomy) over the 2 years of study. Another study (2015) by this group found higher quality of life at 24 months following canaloplasty than trabeculectomy in a questionnaire survey of 327 patients.¹⁰ Canaloplasty patients had a higher positive postoperative mood, higher satisfaction with surgical results, and lower rates of visual and nonvisual symptoms and stress caused by surgery or postsurgical treatment. Difficulties with activities of daily living (e.g., reading) and complaints (e.g., eye burning) were significantly lower in the canaloplasty group. Some questions used were not from validated quality of life questionnaires.

Case Series
Most of the primary literature on canaloplasty consists of case series that have compared posttreatment with pretreatment intraocular pressure. For example, a retrospective comparative study by Ayyala et al. (2011) 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 follow-up of 12 months.¹¹ This study group was drawn from 243 patients who underwent surgery during the same 2-year period (87 canaloplasty procedures, 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 postsurgery, mean reduction in intraocular pressure from preoperative values was 32% for canaloplasty and 43% for trabeculectomy (p = 0.072). Intraocular pressure was slightly lower in the trabeculectomy group (11.6 mm Hg vs. 13.8 mm Hg; p = 0.03), and fewer patients in that group needed postoperative glaucoma medications. There was no significant difference in surgical reoperation rates between the 2 procedures (15% canaloplasty vs. 11% trabeculectomy). This study had a potential for patient selection bias. Only a minority of surgical patients had 12-month follow-up data, and treatment group assignment depended on insurance status.

Lewis et al. (2007) reported on interim data analysis from a manufacturer-sponsored multicenter (15 centers) safety and efficacy study on canaloplasty using the iTrack microcatheter1² with 2- and 3-year results reported in 2009 and 2011.^13,14 The 2011 study included 157 patients with a diagnosis of primary open-angle glaucoma, pigmentary glaucoma, exfoliative glaucoma, and a baseline intraocular pressure of 16 mm Hg or higher before surgery, with a history of intraocular pressure 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, mean intraocular pressure was 23.8 mm Hg, and patients were on an average of 1.8 medications. Canaloplasty was successful in 133 (85%) eyes. Eyes that did not have placement of a tensioning suture were viscodilated to the extent possible by catheterizing the canal from both ostia. Some of the more common early surgical and postoperative complications included microhyphema (12%), hyphema (10%), elevated intraocular pressure (6%), and Descemet membrane detachment (3%). More common late postoperative complications included cataracts (12.7%) and transient intraocular pressure elevation (6.4%). At 3 years postoperatively, 134 study eyes (85% follow-up) had a mean intraocular pressure of 15.2 mm Hg and mean glaucoma medication use of 0.8 medications; 66 (49.3%) eyes were on no medications. Another 7 (4.4%) patients had additional glaucoma surgery. With qualified success defined as achieving an intraocular pressure of 18 mm Hg or lower (with 0 – 2 medications), success was achieved in 69 (77.5%) of the 89 eyes that had successful suture implantation alone and in 24 (89%) of the 27 eyes with successful suture placement combined with phacoemulsification.

Additional reports from this group of investigators included interim 1-year results (2008) for 40 patients who had combined canaloplasty and cataracts surgery (potential overlap in patients from the study described earlier)¹⁵ and a within-subject comparison (2012) in 15 patients who participated in the trial described earlier who had bilateral primary open-angle glaucoma and received canaloplasty in 1 eye and viscocanalostomy in the contralateral eye.¹⁶ For the canaloplasty eye, intraocular pressure decreased from 26.5 mm Hg on 2.1 medications to 14.5 mm Hg on 0.3 medications. For the viscocanalostomy eye, intraocular pressure decreased from 24.3 mm Hg on 1.9 medications to 16.1 mm Hg on 0.4 medications. Reduction in intraocular pressure from baseline was significantly greater with canaloplasty (12.0 mm Hg) than with viscocanalostomy (8.2 mm Hg; p = 0.02). No losses in visual acuity or adverse events were reported for either procedure. The investigators noted that this study evaluated the effects of 2 other maneuvers associated with canaloplasty: (1) 360° viscodilation of Schlemm canal, as opposed to partial dilation achieved with viscocanalostomy, and (2) prolonged opening and tensioning of Schlemm canal with suture placement.16,

The same investigators also reported on an industry-sponsored, 3-year prospective, multicenter study (2011) of 109 open-angle glaucoma patients (109 eyes) who underwent canaloplasty or combined cataract-canaloplasty surgery.¹⁷ All patients had documented visual field loss and met criteria for diagnosis of glaucoma and failure of prior medical or laser therapy. A tensioning suture was successfully placed in 98 (89.9%) eyes, and 96 (88.1%) eyes completed the 3-year follow-up. Of the 13 patients who did not complete follow-up, 4 (3.7%) had additional glaucoma surgery; they were not included in the analysis. In eyes treated with canaloplasty with a successful tensioning suture, intraocular pressure decreased from 23 mm Hg on 1.9 medications to 15.1 mm Hg on 0.9 medications. In eyes treated with combined cataract-canaloplasty surgery with a successful tensioning suture, intraocular pressure decreased from 24.3 mm Hg on 1.5 medications to 13.8 mm Hg on 0.5 medications. For the 11 eyes that had canaloplasty without suture placement, intraocular pressure decreased from 24.4 mm Hg on 1.9 medications to 15.6 mm Hg on 1.2 medications. Late postoperative complications included cataracts (19.1%) and transient intraocular pressure elevation (1.8%).

A prospective series with 60 consecutive Black South African patients with primary open-angle glaucoma who underwent canaloplasty was reported by Grieshaber et al. (2010).18, Mean preoperative intraocular pressure was 45 mm Hg. At 12-month follow-up, intraocular pressure was 15 mm Hg (n = 54); at 36 months, intraocular pressure was 13 mm Hg (n = 49). Eleven (18%) patients were lost to follow-up at 3 years. With qualified success defined as achieving an intraocular pressure of 21 mm Hg or lower (with or without medications), success was achieved in 40 (82%; 95% CI not reported) of 49 patients. When defined as an intraocular pressure of 16 mm Hg or less without medications, 47% (95% CI, 36% to 62%) of eyes met criteria for complete success at 36 months. There were no severe complications in this series.

Three-year follow-up from an independent series of 214 patients treated with canaloplasty in Europe was reported by Brusini (2014).¹⁹ Mean intraocular pressure was reduced from 29.4 mm Hg at baseline to 17.0 mm Hg, after excluding 17 (7.9%) patients who later underwent trabeculectomy. At 3 years, intraocular pressure 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%. There was a decrease in mean medication use, from 3.3 at baseline to 1.3 at follow-up. Complications, which included hyphema, Descemet membrane detachment, intraocular pressure spikes, and hypotony, were fewer than typically seen with trabeculectomy. Several disadvantages of the procedure were noted, including the inability to complete the procedure in 16.4% of eyes.

Voykov et al. (2015) reported on 5-year follow-up on patients (20 eyes) with open-angle glaucoma who underwent canaloplasty at a single center in Germany.²⁰ Mean intraocular pressure decreased from 25.7 mm Hg at baseline (n = 33) to 15.5 mm Hg (n = 19) at 1 year, 15.1 mm Hg (n = 18) at 3 years, and 14.2 mm Hg (n = 18) at 5 years. At each time point, reductions in mean intraocular pressure were statistically significant versus baseline (p < 0.001). Mean number of medications used was 3.4 at baseline, 1.5 at 1 year, 1.6 at 3 years, and 1.7 at 5 years. At each time point, medication use was significantly lower than baseline (p < 0.001). Thirteen (65%) of 20 eyes underwent another surgical procedure due to inadequate intraocular pressure control. Median length of time before additional surgery was 24 months (95% CI, 1 to 51 months). The complication rate was low, with the most common being hyphema (7/20 [35%] eyes). No sight-threatening complications were reported.

Other case series have evaluated ab interno canaloplasty via the use of the iTrack^21,22 or OMNI surgical systems^23,24,25,26 in patients with mild-to-moderate primary open-angle glaucoma as a standalone procedure or in combination with cataract surgery. Two studies of the OMNI system evaluating a total of 267 eyes with uncontrolled baseline intraocular pressure (IOP) reported mean reductions in IOP and medication use ranging between 5.5 to 6.4 mmHg and 0.6 to 1.1 medications, respectively, over 12 – 36 months of follow-up.^23,24 Results from the smaller GEMINI study of 120 patients treated with the OMNI system reported an IOP reduction of 8.2 mmHg and a mean decrease of 1.4 medications over 12 months, with 75% of participants achieving a mean IOP ≤ 18 mmHg; however, analysis was based on mean diurnal ocular pressure following medication washout at baseline, and it is unclear what proportion of patients initially had uncontrolled IOP on medication.²⁵ A subgroup analysis of 39 Hispanic participants in the GEMINI study, a demographic disproportionally affected by primary open-angle glaucoma in the U.S., showed comparable results, with a mean IOP decrease of 7.9 and no need for continued medication use in 87%.²⁶ One small study utilizing the OMNI system in 27 patients previously treated with the iStent trabecular microbypass stent reported a mean IOP reduction of 5.1 mmHg and a mean decrease of 0.4 medications.²⁷ Two studies of the iTrack system evaluated a total of 71 eyes treated with canaloplasty alone or in combination with cataract surgery and reported 36 to 48 month outcomes.21,22, Mean IOP reductions ranged from 5.2 to 7.2 mmHg and medication use decreased between 1 to 1.5 medications. Overall, 68.2%% to 77.2% of participants were using ≤ 1 medication at final follow-up. No serious complications were reported across studies utilizing the iTrack or OMNI systems.

Section Summary: Canaloplasty
Findings from a small RCT and a comparative effectiveness review have indicated that trabeculectomy is generally superior to canaloplasty for lowering intraocular pressure; however, the procedure has been associated with more serious complication rates. Another study has reported that canaloplasty resulted in improved quality of life outcomes at 2 years relative to trabeculectomy, although not all quality of life measures derived from validated questionnaires. Additionally, several, small, industry-sponsored case series comparing pre- with posttreatment results of canaloplasty alone or in combination with cataract surgery have shown that most patients achieved sufficient intraocular pressure lowering with reduced need for continued medication and relatively few complications.

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Clinical Input From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests on viscocanalostomy, input was received from 1 specialty medical society and 3 academic medical centers while this policy was under review in 2011. Although some considered viscocanalostomy to be medically necessary in a select group of patients who would be at risk for suffering a blinding complication with trabeculectomy, input was mixed. For example, 1 reviewer considered outcomes with viscocanalostomy to be inferior to other currently used nonpenetrating techniques.

In response to requests on canaloplasty, input was received from 1 specialty medical society and 2 academic medical centers while this policy was under review in 2011. One ophthalmology association provided a statement indicating that the case series cited are sufficient to show efficacy of canaloplasty to lower intraocular pressure to treat open-angle glaucoma. Other reviewers considered canaloplasty to be investigational but medically necessary for a select group of patients (e.g., patients at risk for infection or hypotony, who have surface disease precluding the creation of good trabeculectomy bleb, or for whom a patch would not cover a glaucoma drainage device implant).

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in "Supplemental Information" if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American Academy of Ophthalmology
A technology assessment from the American Academy of Ophthalmology (2011) included canaloplasty in its review of novel glaucoma procedures.²⁸ The Academy concluded that all the techniques and devices reviewed were still in the initial stage (≤ 5 years) of clinical experience and lacked widespread use, with only level III evidence (cohort studies) supporting the procedures. In addition to describing potential advantages and disadvantages of the procedure, it was noted that the long-term effects of a foreign body in the Schlemm canal are not known.

National Institute for Health and Care Excellence
In 2017, the National Institute for Health and Care Excellence (NICE) updated its 2008 guidance on ab externo canaloplasty for primary open-angle glaucoma.^29,30 The current recommendation is that the “evidence on the safety and efficacy of ab externo canaloplasty for primary open-angle glaucoma is adequate is support the use of this procedure...”

Similarly, in 2017 (amended in 2022), NICE updated its 2009 guidance on the diagnosis and management of chronic open-angle glaucoma.^31,32 When comparing penetrating surgery (trabeculectomy) with nonpenetrating surgery (deep sclerectomy and viscocanalostomy), NICE found moderate-quality evidence that trabeculectomy is more effective than nonpenetrating surgery in reducing the number of eyes with an unacceptable intraocular pressure, but was more likely to cause cataract formation and persistent hypotony at 12- to 36-month follow-up. There was very low quality evidence that trabeculectomy is more effective than nonpenetrating surgery in reducing intraocular pressure from baseline to 6- and 12-month follow-up, but the effect size might have been too small to be clinically significant. The guidance recommended offering information on the risks and benefits associated with surgery and offering surgery (type not specified) with pharmacologic augmentation to people with chronic open-angle glaucoma at risk of progressing to sight loss, despite treatment (recommendation 1.4.21).

In 2022, NICE published an interventional procedures guidance on ab interno canaloplasty for open-angle glaucoma.³³ The current recommendation states that "evidence on the safety of ab interno canaloplasty for open-angle glaucoma shows no major safety concerns. Evidence on the efficacy is limited in quality and quantity, particularly in the long term. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research."

U.S. Preventive Services Task Force Recommendations
Not applicable.

Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in Table 1.

Table 1. Summary of Key Trials

NCT: national clinical trial.
a Denotes industry-sponsored or cosponsored trial.

References:   

1. Allison K, Patel DG, Greene L. Racial and Ethnic Disparities in Primary Open-Angle Glaucoma Clinical Trials: A Systematic Review and Meta-analysis. JAMA Netw Open. May 03 2021; 4(5): e218348. PMID 34003274
2. Chai C, Loon SC. Meta-analysis of viscocanalostomy versus trabeculectomy in uncontrolled glaucoma. J Glaucoma. 2010; 19(8): 519-27. PMID 20179632
3. Eldaly MA, Bunce C, Elsheikha OZ, et al. Non-penetrating filtration surgery versus trabeculectomy for open-angle glaucoma. Cochrane Database Syst Rev. Feb 15 2014; (2): CD007059. PMID 24532137
4. Gilmour DF, Manners TD, Devonport H, et al. Viscocanalostomy versus trabeculectomy for primary open angle glaucoma: 4-year prospective randomized clinical trial. Eye (Lond). Sep 2009; 23(9): 1802-7. PMID 17293790
5. Kobayashi H, Kobayashi K, Okinami S. A comparison of the intraocular pressure-lowering effect and safety of viscocanalostomy and trabeculectomy with mitomycin C in bilateral open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol. May 2003; 241(5): 359-66. PMID 12698257
6. Grieshaber MC, Peckar C, Pienaar A, et al. Long-term results of up to 12 years of over 700 cases of viscocanalostomy for open-angle glaucoma. Acta Ophthalmol. Jun 2015; 93(4): 362-7. PMID 25270165
7. Stangos AN, Mavropoulos A, Leuenberger PM, et al. The effect of learning curve on the surgical outcome of viscocanalostomy. J Glaucoma. Aug 2012; 21(6): 408-14. PMID 21673593
8. Mosaed S, Dustin L, Minckler DS. Comparative outcomes between newer and older surgeries for glaucoma. Trans Am Ophthalmol Soc. Dec 2009; 107: 127-33. PMID 20126489
9. Matlach J, Dhillon C, Hain J, et al. Trabeculectomy versus canaloplasty (TVC study) in the treatment of patients with open-angle glaucoma: a prospective randomized clinical trial. Acta Ophthalmol. Dec 2015; 93(8): 753-61. PMID 25847610
10. Klink T, Sauer J, Körber NJ, et al. Quality of life following glaucoma surgery: canaloplasty versus trabeculectomy. Clin Ophthalmol. 2015; 9: 7-16. PMID 25565763
11. Ayyala RS, Chaudhry AL, Okogbaa CB, et al. Comparison of surgical outcomes between canaloplasty and trabeculectomy at 12 months' follow-up. Ophthalmology. Dec 2011; 118(12): 2427-33. PMID 21856008
12. Lewis RA, von Wolff K, Tetz M, et al. Canaloplasty: circumferential viscodilation and tensioning of Schlemm's canal using a flexible microcatheter for the treatment of open-angle glaucoma in adults: interim clinical study analysis. J Cataract Refract Surg. Jul 2007; 33(7): 1217-26. PMID 17586378
13. Lewis RA, von Wolff K, Tetz M, et al. Canaloplasty: circumferential viscodilation and tensioning of Schlemm canal using a flexible microcatheter for the treatment of open-angle glaucoma in adults: two-year interim clinical study results. J Cataract Refract Surg. May 2009; 35(5): 814-24. PMID 19393879
14. Lewis RA, von Wolff K, Tetz M, et al. Canaloplasty: Three-year results of circumferential viscodilation and tensioning of Schlemm canal using a microcatheter to treat open-angle glaucoma. J Cataract Refract Surg. Apr 2011; 37(4): 682-90. PMID 21420593
15. Shingleton B, Tetz M, Korber N. Circumferential viscodilation and tensioning of Schlemm canal (canaloplasty) with temporal clear corneal phacoemulsification cataract surgery for open-angle glaucoma and visually significant cataract: one-year results. J Cataract Refract Surg. Mar 2008; 34(3): 433-40. PMID 18299068
16. Koerber NJ. Canaloplasty in one eye compared with viscocanalostomy in the contralateral eye in patients with bilateral open-angle glaucoma. J Glaucoma. Feb 2012; 21(2): 129-34. PMID 21278587
17. Bull H, von Wolff K, Körber N, et al. Three-year canaloplasty outcomes for the treatment of open-angle glaucoma: European study results. Graefes Arch Clin Exp Ophthalmol. Oct 2011; 249(10): 1537-45. PMID 21732110
18. Grieshaber MC, Pienaar A, Olivier J, et al. Canaloplasty for primary open-angle glaucoma: long-term outcome. Br J Ophthalmol. Nov 2010; 94(11): 1478-82. PMID 20962352
19. Brusini P. Canaloplasty in open-angle glaucoma surgery: a four-year follow-up. ScientificWorldJournal. 2014; 2014: 469609. PMID 24574892
20. Voykov B, Blumenstock G, Leitritz MA, et al. Treatment efficacy and safety of canaloplasty for open-angle glaucoma after 5 years. Clin Exp Ophthalmol. Nov 2015; 43(8): 768-71. PMID 25952140
21. Gallardo MJ. 36-Month Effectiveness of Ab-Interno Canaloplasty Standalone versus Combined with Cataract Surgery for the Treatment of Open-Angle Glaucoma. Ophthalmol Glaucoma. 2022; 5(5): 476-482. PMID 35183815
22. Koerber N, Ondrejka S. Four-Year Efficacy and Safety of iTrack Ab-interno Canaloplasty as a Standalone Procedure and Combined with Cataract Surgery in Open-Angle Glaucoma. Klin Monbl Augenheilkd. Apr 14 2022. PMID 35426107
23. Murphy Iii JT, Terveen DC, Aminlari AE, et al. A Multicenter 12-Month Retrospective Evaluation of Canaloplasty and Trabeculotomy in Patients with Open-Angle Glaucoma: The ROMEO 2 Study. Clin Ophthalmol. 2022; 16: 3043-3052. PMID 36128338
24. Ondrejka S, Körber N, Dhamdhere K. Long-term effect of canaloplasty on intraocular pressure and use of intraocular pressure-lowering medications in patients with open-angle glaucoma. J Cataract Refract Surg. Dec 01 2022; 48(12): 1388-1393. PMID 35796586
25. Gallardo MJ, Pyfer MF, Vold SD, et al. Canaloplasty and Trabeculotomy Combined with Phacoemulsification for Glaucoma: 12-Month Results of the GEMINI Study. Clin Ophthalmol. 2022; 16: 1225-1234. PMID 35493971
26. Gallardo MJ, Dhamdhere K, Dickerson JE. Canaloplasty and Trabeculotomy Ab Interno Combined with Cataract Surgery: 12-Month Outcomes in Hispanic Patients with Open-Angle Glaucoma. Clin Ophthalmol. 2022; 16: 905-908. PMID 35356700
27. Terveen DC, Sarkisian SR, Vold SD, et al. Canaloplasty and trabeculotomy with the OMNI ® surgical system in OAG with prior trabecular microbypass stenting. Int Ophthalmol. Oct 13 2022. PMID 36229561
28. Francis BA, Singh K, Lin SC, et al. Novel glaucoma procedures: a report by the American Academy of Ophthalmology. Ophthalmology. Jul 2011; 118(7): 1466-80. PMID 21724045
29. National Institute for Health and Care Evidence (NICE). Ab externo canaloplasty for primary open-angle glaucoma [IPG591]. 2017; https://www.nice.org.uk/guidance/ipg591. Accessed January 30, 2023.
30. National Institute for Health and Care Evidence (NICE). Canaloplasty for primary open-angle glaucoma [IPG260]. 2008; https://www.nice.org.uk/guidance/ipg260. Accessed January 29, 2023.
31. National Institute for Health and Care Excellence (NICE). Glaucoma: diagnosis and management [NG81]. 2017; https://www.nice.org.uk/guidance/NG81. Accessed January 28, 2023.
32. National Institute for Health and Care Excellence (NICE). Glaucoma: diagnosis and management of chronic open angle glaucoma and ocular hypertension [CG85]. 2009; https://www.nice.org.uk/guidance/cg85. Accessed January 27, 2023.
33. National Institute for Health and Care Excellence (NICE). Ab interno canaloplasty for open-angle glaucoma [IPG745]. 2022; https://www.nice.org.uk/guidance/ipg745. Accessed January 26, 2023.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

"Current Procedural Terminology © American Medical Association. All Rights Reserved" 

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