Viscocanalostomy and Canaloplasty

Number: 0435

Policy

Aetna considers canaloplasty medically necessary for the treatment of primary open-angle glaucoma (POAG), including normal-tension glaucoma, and for pseudoexfoliation glaucoma.

Aetna considers canaloplasty experimental and investigational for all other indications (e.g., for use in corticosteroid-induced glaucoma, glaucoma gene therapy and uveitic glaucoma) because its effectiveness for indications other than the one listed above has not been established.

Aetna considers viscocanalostomy (including phacoviscocanalostomy) experimental and investigational for the treatment of primary open-angle glaucoma or any other indications because there is insufficient evidence in the peer-reviewed medical literature of the effectiveness of this procedure.

Aetna considers combined phacoemulsification and viscocanalostomy with Ologen implant for co-existing cataract and POAG experimental and investigational because the effectiveness of this approach has not been established.

Aetna considers canaloplasty and trabeculotomy ab interno with the OMNI System combined with cataract surgery experimental and investigational for the treatment of POAG because the effectiveness of this approach has not been established.

Aetna considers combined gonioscopy-assisted transluminal trabeculotomy (GATT) with ab interno canaloplasty (ABiC) in conjunction with phacoemulsification experimental and investigational for the treatment of POAG because the effectiveness of this approach has not been established.

See also CPB 0484 - Glaucoma Surgery.

Background

Glaucoma is an irreversible group of conditions/diseases involving death of the nerve cells in front of the optic nerve. It was once thought that glaucoma was generally due to increased intra-ocular pressure (IOP); however, the condition is also found in individuals with normal or low eye pressure. Therefore, diagnosis of glaucoma does not rely on increased IOP and may be related to optic nerve damage. Glaucoma is one of the leading causes of blindness with loss of peripheral vision being a hallmark sign of glaucoma.

Medication, in the form of eye drops, pills or both, is the most common early treatment for glaucoma. There are numerous medications available for treating glaucoma; all of which must be taken regularly. If medication fails, other interventions may be recommended.

Current standard surgical treatments for glaucoma include trabeculectomy or trabeculoplasty (incisional or laser). Iridotomy, iridectomy or iridoplasty may be necessary for angle-closure glaucoma.

Viscocanalostomy is an ophthalmic surgical procedure that has been developed as an alternative to trabeculectomy.  In some cases, viscocanalostomy has been used in conjunction with cataract removal via phaco-emulsification. Viscocanalostomy issimilar to canaloplasty in that tissue flaps are cut in the conjunctiva and the sclera. The creation of these flaps exposes a portion of the drainage (Schlemm’s) canal into which a high-viscosity elastic gel is injected. The injected material opens and enlarges the canal to allow increased fluid flow out of the anterior chamber. The tissue flaps are then closed. 

Although there are a variety of viscocanalostomy techniques, the procedure basically involves production of superficial and deep scleral flaps, excision of the deep scleral flap to create a scleral reservoir, and unroofing of Schlemm's canal.  A high-viscosity viscoelastic, such as sodium hyaluronate, is used to open the canal and create a passage from a scleral reservoir to the canal. The superficial scleral flap is then sutured water tight, trapping the viscoelastic until healing takes place.  However, the peer-reviewed published medical literature reveals that viscocanalostomy has only been studied in a relatively small number of patients at a few centers.  There are no published peer-reviewed data on long-term outcomes of viscocanalostomized patients, and what few clinical studies have been published directly comparing viscocanalostomy with trabeculectomy show that trabeculectomy is more effective at lowering intra-ocular pressure (IOP).

Randomized controlled multi-center clinical trials directly comparing viscocanalostomy with trabeculectomy are needed before viscocanalostomy can be accepted as an established alternative to trabeculectomy.  As one of the leading investigators of viscocanalostomy in North America commented: "As with all glaucoma studies, long term follow-up evaluation will be required to prove its [viscocanalostomy's] real efficacy.  In addition, randomized studies which would compare viscocanalostomy and phacoemulsification with other combined glaucoma procedures are also in order" (Henahan, 1998).

In a technology assessment on non-penetrating glaucoma surgery, the American Academy of Ophthalmology (AAO, 2001) stated that non-penetrating glaucoma surgery (viscocanalostomy is one of the 2 major variations of this procedure) has the potential to reduce IOP) while minimizing the risk of post-operative relative hypotony and the complications associated with hypotony.  The authors found, however, that the majority of the published literature on non-penetrating glaucoma surgery contains information from case series, which are not randomized and lack a control group.  The authors concluded that randomized clinical trials (RCTs) are needed to assess these procedures and to determine their role in the clinical management of glaucoma patients.

The AAO's practice guideline on the management of primary open-angle glaucoma (2005) recognized viscocanalostomy as being a non-penetrating surgery used by some physicians as an alternative to trabeculectomy, but it stated that the precise role of non-penetrating surgeries (i.e., viscocanalostomy and non-penetrating deep sclerectomy) has yet to be determined.

Shaarawy and associates (2003) studied prospectively the success rate and complications of viscocanalostomy in patients with medically uncontrolled primary and secondary open angle glaucoma (n = 57).  These investigators concluded that viscocanalostomy appears to be a promising modification of filtering surgery.

Randomized controlled clinical studies comparing viscocanalostomy with trabeculectomy in glaucomatous patients have shown that trabeculectomy is more effective in lowering IOP than viscocanalostomy.  In a RCT (n = 20) comparing viscocanalostomy and trabeculectomy for the treatment of patients with open angle glaucoma, Jonescu-Cuypers et al (2001) found that trabeculectomy was more effective than viscocanalostomy in lowering IOP in glaucomatous eyes of such patients.  This is in agreement with the finding of Luke et al (2002) who examined the IOP-lowering effectiveness and the post-operative complication profile of viscocanalostomy versus trabeculectomy in a prospective randomized trial (n = 60).  The authors concluded that in eyes with open-angle glaucoma, viscocanalostomy is less effective in reducing IOP than standard filtering surgery.  However, post-operative complications are less frequent after viscocanalostomy.  In a prospective clinical study, Kobayashi and colleagues (2003) compared the IOP-lowering effect and safety of viscocanalostomy and trabeculectomy with mitomycin C in patients with bilateral primary open-angle glaucoma (n = 25).  The eyes of each patient were randomly assigned to receive viscocanalostomy in 1 eye and trabeculectomy with mitomycin C in the other eye.  The patients were followed-up for 12 months.  These researchers reported that trabeculectomy with mitomycin C may be more effective than viscocanalostomy in lowering IOP in patients with primary open-angle glaucoma, while eyes undergoing viscocanalostomy experience a lower incidence of complications, and they stated that further investigation of more cases is needed.

In a single-masked, parallel-group, prospective, randomized 24-month trial, Carassa et al (2003) compared the effectiveness and safety of viscocanalostomy and trabeculectomy in adults with uncontrolled open-angle glaucoma (n = 50).  Eyes were assigned randomly to either viscocanalostomy (group 1) or trabeculectomy (group 2) with no intraoperative anti-fibrotics in the study eye.  In group 1, no further intervention was allowed, whereas trabeculectomy eyes could receive subconjunctival 5-fluorouracil (5-FU) injections or laser suture lysis after surgery.  It was found that viscocanalostomy is an effective IOP-lowering procedure in adults affected by open-angle glaucoma.  Trabeculectomy with post-operative 5-FU can probably provides lower IOPs but, with more numerous complications, greater discomfort, and more intensive post-operative management.  The authors concluded that large, multi-center controlled studies are needed to define the role of viscocanalostomy in the surgical management of glaucoma.

An assessment prepared for the Cochrane Collaboration comparing surgical and medical management of glaucoma found no studies comparing viscocanalostomy with medical management (Burr et al, 2004).  The assessment noted that although viscocanalostomy may have fewer complications than trabeculectomy, viscocanalostomy may have limited effectiveness at lowering IOP. 

Guidelines from the Royal College of Ophthalmologists (2004) conclude that "[a]t the present time there is insufficient evidence from prospective studies that these operations [viscocanalostomy and deep sclerectomy] have a lower incidence of long-term complications while maintaining good IOP control to advocate their use in routine glaucoma practice."

In a prospective randomized 1-year study, Kobayashi and Kobayashi (2007) compared the IOP-lowering effect of combined viscocanalostomy and phaco-emulsification and combined trabeculectomy and phaco-emulsification with mitomycin C in eyes with primary open-angle glaucoma.  A total of 40 consecutive patients (40 eyes) with primary open-angle glaucoma and cataract were enrolled in this study.  Eyes were assigned randomly either to trabeculectomy with mitomycin C or to viscocanalostomy in combination with phaco-emulsification and intra-ocular lens implantation.  Mean baseline IOP was 24.0 +/- 2.0 mm Hg in the viscocanalostomy group and 23.7 +/- 2.6 mm Hg in the trabeculectomy group (p = 0.7).  Mean post-operative IOP was 13.7 +/- 2.2 mm Hg at 3 months, 14.8 +/- 3.3 mm Hg at 6 months, and 14.9 +/- 3.0 mm Hg at 12 months in the viscocanalostomy group and 12.1 +/- 4.0 mm Hg at 3 months, 13.8 +/- 4.7 mm Hg at 6 months, and 14.1 +/- 4.4 mm Hg at 12 months in the trabeculectomy group.  There was no significant difference in the mean IOP between the groups at any time.  At 12 months, 17 patients (85 %) in the viscocanalostomy group and 16 patients (80 %) in the trabeculectomy group achieved an IOP of 20 mm Hg or less without medication (p = 0.7).  Complications included 2 cases (10 %) of flat/shallow anterior chamber and 4 cases (20 %) of hypotony in the trabeculectomy group, whereas intra-operative microperforation of Descemet's membrane occurred in 3 cases (15 %) in the viscocanalostomy group.  The authors concluded that there was no significant difference in IOP reduction between viscocanalostomy and trabeculectomy with mitomycin C in combination with phaco-emulsification and intra-ocular lens implantation in patients with primary open-angle glaucoma.  They also stated that future study of a large population is needed to verify these observations.

In a long-term, prospective, randomized study, Gilmour et al (2007) compared the lowering effects of viscocanalostomy and trabeculectomy without anti-metabolite on IOP.  The results of this study showed that at 40-month follow-up, trabeculectomy was more likely to achieve IOP levels below 18 mm Hg than viscocanalostomy.  The study enrolled 21 primary open angle glaucoma patients who underwent trabeculectomy and 22 who underwent viscocanalostomy by a single surgeon familiar with both procedures.  The mean pre-operative IOP was 25 mm Hg, and the trabeculectomies were performed without anti-metabolite intra-operatively, although some patients received 5-FU in the post-operative period.  The follow-up period was 4 years, and the post-operative treatment was similar in both groups.

Survival analysis suggested that patients who underwent trabeculectomy had a 42 % chance of experiencing lower IOP compared to a 21 % chance in the viscocanalostomy group at 40 months.  Success was defined as IOP below 18 mm Hg, and qualified success was IOP below 18 with medications.  The trabeculectomy group, however, had more complications, and interventions such as needling and 5-FU injections were needed in the early post-operative period.  Although the trabeculectomy group was less likely to need glaucoma medications to control IOP in the post-operative period, IOP with medication was well-controlled in the viscocanalostomy group.  Of interest, only 1 patient required goniopuncture in the viscocanalostomy group compared to other studies in the literature where goniopuncture was required for around 30 % of patients.  It is unclear how this might have influenced the results.

The authors stated that the findings of this study confirmed previous reports that the likelihood of obtaining lower IOP over the long-term with viscocanalostomy is lower than that with a standard trabeculectomy.  The re-introduction of canal based surgery in adults has generated intense interest in the glaucoma community to develop new approaches to improve filtration through the trabecular and other pathways.  They noted that prospective, randomized, long-term, clinical trials will hopefully provide some insight as to which of these new procedures might be most beneficial to glaucoma patients.

More recently, a glaucoma canaloplasty (enhanced viscocanalostomy) has been introduced, which involves modification of the viscocanalostomy procedure.  Canaloplasty uses viscoelastic and a specialized microcatheter (e.g., iScience Surgical Ophthalmic Microcannula, Menlo Park, CA) to forceably open the Schlemm's canal.  The procedure is intended to restore the natural drainage of fluid from the eye, thus reducing IOP in persons with glaucoma.

Canaloplasty is a surgical procedure in which tissue flaps are cut in the conjunctiva and the sclera to expose the drainage area (Schlemm’s canal). Canaloplasty attempts to open the entire drainage area surrounding the anterior chamber (360^°) instead of just a portion of it, as in viscocanalostomy below. A very small catheter is placed in the opening and used to inject the high-viscosity elastic gel into the entire drainage area forming a ring around the anterior chamber. A suture loop is left in the canal to help maintain tension and keep the canal open. The canal is expanded by the injection to promote better fluid drainage.

Similar to the viscocanalostomy, canaloplasty is completed under a scleral flap.  The canal is identified then intubated with a flexible microcatheter which has a lighted tip to identify its location as it passes through the Schlemm's canal.  The microcatheter also has a lumen to allow for the passage of high viscosity sodium hyaluronate for dilation of the canal.  Once the cannula has passed the full length (360º through) of the Schlemm's canal, a suture is tied to the cannula and as the cannula is withdrawn the suture is tied off and left in place.  The intracanalicular suture cinches and stretches the trabecular meshwork inwards and permanently opening the Schlemm's canal.  The scleral flap is tightly closed as well as the conjunctiva.  Before, during and after the surgery, a special ultrasound imaging system is used to help identify the canal and the instrumentation in the canal.

An important difference between viscocanalostomy and canaloplasty is that canaloplasty aims at opening the entire length of the Schlemm's canal, not just one section of it.  Canaloplasty is currently under investigation.  Several trials are currently underway to further support the benefits and safety of this technique.

Although a relatively new procedure, canaloplasty seems effective in lowering IOP when used in glaucoma patients as an alternative to trabeculectomy.  The choice between these procedures relates to the degree of IOP lowering required by a patient as well as the patient's risk factors for complications.  Canaloplasty will likely be used most often in earlier stages of glaucoma and in patients in whom bleb infection and leakage would put them at higher risk for infection-associated blindness (endophthalmitis).  This procedure may also be indicated in patients who may not need IOP-lowering to the degree that is achievable with trabeculectomy.  Canaloplasty and other procedures that lower IOP without creating an aqueous filtering hole in the eye with a conjunctival bleb may have an increasing role in the surgical management of patients with glaucoma because of their potentially improved safety profile.

In an international multi-center prospective study (14 sites in Geramny and in the United States of America), Lewis et al (2007) assessed the safety and effectiveness of circumferential viscodilation and tensioning of the inner wall of Schlemm's canal (canaloplasty) for the treatment of open-angle glaucoma (OAG).  Adult patients having glaucoma surgery, patients with qualifying pre-operative IOP of at least 16 mm Hg or higher and open angles were eligible.  Evaluation was performed at baseline and 1 day, 1 week, and 1, 3, 6, and 12 months post-operatively.  After a non-penetrating dissection technique to expose Schlemm's canal was performed, a flexible microcatheter was used to dilate the full circumference of the canal by injecting sodium hyaluronate 1.4 % during catheterization.  A suture loop was placed in the canal to apply tension to the trabecular meshwork.  High-resolution ultrasound imaging was used to evaluate Schlemm's canal and anterior segment angle morphology, including distension of the trabecular meshwork caused by the tensioning suture.  Data analysis was performed in 2 groups: Group 1, in which patients met all inclusion criteria, and Group 2, made up of Group 1 patients who had successful suture placement.  Group 1 comprised 94 patients and Group 2, 74 patients.  The mean baseline IOP in Group 1 was 24.7 mm Hg +/- 4.8 (standard deviation [SD]) on a mean of 1.9 +/- 1.0 medications per patient.  In Group 2 (patients with sutures), the mean IOP was 16.1 +/- 4.7 mm Hg 3 months post-operatively, 15.6 +/- 4.0 mm Hg at 6 months, and 15.3 +/- 3.8 mm Hg at 1 year.  Medication use dropped to a mean of 0.6 +/- 0.9 per patient at 12 months.  Suture tensioning was an apparent contributing factor in achieving surgical success.  Patients with measurable trabecular meshwork distension from suture tension had a mean IOP of 15.9 +/- 5.2 mm Hg at 6 months and 14.5 +/- 3.0 mm Hg at 12 months.  Surgical and post-surgical adverse events were reported in 15 of 94 patients (16 %) and included hyphema (n = 3), elevated IOP greater than 30 mm Hg (n = 3), Descemet's tear (n = 1), hypotony (n = 1), choroidal effusion (n = 1), and exposed closure suture with eyelid edema and erythema epiphora (n = 1); 4 patients were subsequently converted to trabeculectomy.  The authors concluded that canaloplasty was a safe and effective procedure to reduce IOP in adult patients with OAG.  The major drawbacks of this study included the lack of randomization and a control group, as well as the learning curve associated with performance of the procedure.  Other limitations include the small, heterogeneous patient group, short-term follow-up, and the number of patients lost to follow-up.

Shingleton et al (2008) evaluated the safety and effectiveness of canaloplasty combined with clear corneal phaco-emulsification and posterior chamber intraocular lens (IOL) implantation in in treating OAG.  This international multi-center prospective study comprised adult patients with OAG having combined glaucoma and cataract surgery.  Patients with qualifying treated pre-operative IOP of at least 21 mm Hg or higher and open angles were eligible.  Evaluation was performed at baseline and 1 day, 1 week, and 1, 3, 6, and 12 months post-operatively.  Intra-operative and post-operative high-resolution ultrasound imaging was used to assess Schlemm canal and anterior segment angle morphology, including distension of the trabecular meshwork due to the tensioning suture.  Data from 54 eyes that had combined glaucoma and cataract surgery performed by 11 surgeons at 9 study sites were analyzed for this interim analysis.  The mean baseline IOP was 24.4 mm Hg +/- 6.1 (SD) with a mean of 1.5 +/- 1.0 medications per eye.  In all eyes, the mean post-operative IOP was 13.6 +/- 3.8 mm Hg at 1 month, 14.2 +/- 3.6 mm Hg at 3 months, 13.0 +/- 2.9 mm Hg at 6 months, and 13.7 +/- 4.4 mm Hg at 12 months.  Medication use dropped to a mean of 0.2 +/- 0.4 per patient at 12 months.  Surgical complications were reported in 5 eyes (9.3 %) and included hyphema (n = 3, 5.6 %), Descemet tear (n = 1, 1.9 %), and iris prolapse (n = 1, 1.9 %).  Transient IOP elevation of more than 30 mm Hg was observed in 4 eyes (7.3 %) 1 day post-operatively.  The authors concluded that canaloplasty combined with clear corneal phaco-emulsification and posterior chamber IOL implantation was a safe and effective procedure to reduce IOP in adult patients with OAG.

The National Institute for Health and Clinical Excellence (NICE, 2008) stated that canaloplasty for the treatment of primary OAG should be used only in the context of research or formal prospective data collection.  It noted that current evidence on the safety and effectiveness of canaloplasty is inadequate in quality and quantity. Specialist advisors to NICE considered theoretical adverse events to include anterior chamber perforation, tearing of Descemet’s membrane resulting in corneal opacification or retinal damage, intra-ocular inflammation caused by the suture, cataract formation, sustained increases in IOP, hypotony, and bleb formation or suture exposure with endophthalmitis.

In a meta-analysis, Hondur and colleagues (2008) evaluated the effectiveness of non-penetrating glaucoma surgery for OAG with respect to target IOP and severity of glaucoma.  Studies encompassing only combined glaucoma and cataract surgery were excluded.  Measurement of effectiveness was determined on the basis of achievement of target IOP.  Data related to post-operative goniopuncture and needling with anti-metabolite application were noted.  The percentage of cases achieving less than or equal to 21 mm Hg was 48.6 % after primary deep sclerectomy (DS), 68.7 % after DS with implant, 67.1 % after DS with anti-metabolite, 51.1 % after primary viscocanalostomy, and 36.8 % after viscocanalostomy with anti-metabolite or implant.  Visual field parameters were almost exclusively not available; whereas cup/disk ratio and target IOP lower than 21 mm Hg were available in very few reports.  With lower set IOP targets, the rates of success varied between 35 % and 86 % for DS, and between 10 % and 67 % for viscocanalostomy.  The mean follow-up of the studies were mostly in the range of 3 years.  The authors concluded that non-penetrating glaucoma surgery seems to provide IOP reduction into the high teens.  Its potential to achieve lower target IOPs seems to be low.  They stated that longer-term studies, with data related to glaucoma severity and proper target IOPs are needed.

Mendrinos et al (2008) noted that non-penetrating glaucoma surgeries have been developed in recent years in order to improve the safety of conventional filtering procedures.  The goal of non-penetrating filtering procedures is to reduce IOP by enhancing the natural aqueous outflow channels, while reducing outflow resistance located in the inner wall of the Schlemm's canal and the juxta-canalicular trabecular meshwork.  In the last few years, viscocanalostomy and DS with external trabeculectomy have become the most popular non-penetrating filtering procedures.  Both involve removal of a deep scleral flap, the external wall of Schlemm's canal and corneal stroma behind the anterior trabeculum and Descemet's membrane, thus creating an intrascleral space.  The aqueous humour leaves the anterior chamber through the intact trabeculo-Descemet's membrane into the scleral space, from where it will egress into different pathways.  The technique is associated with a long learning curve.  Published clinical trials comparing non-penetrating glaucoma surgery to full-thickness trabeculectomy have a consensus on the superior safety profile of non-penetrating glaucoma surgery but are not in agreement when it comes to efficacy, where conflicting results have been found.

Lewis and colleagues (2009) assessed 2-year post-surgical safety and efficacy of canaloplasty (circumferential viscodilation and tensioning of the inner wall of Schlemm canal) to treat OAG.  This international prospective study comprised adult OAG patients having glaucoma surgery or combined glaucoma-cataract surgery.  Qualifying pre-operative IOP was at least 16 mm Hg and historical IOP, at least 21 mm Hg.  The full circumference of the canal was viscodilated and a trabecular tensioning suture placed with a micro-catheter.  Primary outcome measures included IOP and glaucoma medication use.  At 24 months, all 127 eyes (127 patients) had a mean IOP of 16.0 mm Hg +/- 4.2 and mean glaucoma medication use of 0.5 +/- 0.8 (baseline values 23.6 +/- 4.8 mm Hg and 1.9 +/- 0.8 medications).  Eyes with canaloplasty alone had a mean IOP of 16.3 +/- 3.7 mm Hg and 0.6 +/- 0.8 medications (baseline values 23.2 +/- 4.0 mm Hg and 2.0 +/- 0.8 medications).  Eyes with combined glaucoma-cataract surgery had a mean IOP of 13.4 +/- 4.0 mm Hg and 0.2 +/- 0.4 medications (baseline values 23.1 +/- 5.5 mm Hg and 1.7 +/- 1.0 medications).  The IOP and medication use results at all time points were statistically significant versus baseline (p < 0.001).  The late post-operative follow-up identified 3 patients with elevated IOP.  No other serious ocular or non-ocular complications were reported.  The authors concluded that canaloplasty was safe and effective in reducing IOP in adult patients with OAG.  These are "interim" results of an ongoing clinical study; the clinical value of canoplasty awaits the completion and final analyses of results.

Griesbacher et al (2010) reported on a prospective study evaluating 32 consecutive eyes that had canaloplasty and at least 1 year of follow-up.  The mean pre-operative IOP (with medications) of 27.3 +/- 5.6 mm Hg improved to a mean post-operative IOP (without medications) of 12.8 +/- 1.5 mm Hg at 12 months.  The success rate where the IOP reached less than 21, less than 18, and less than 16 mm Hg was 93.8 % (95 % confidence interval [CI]: 0.86 to 1.0), 84.4 % (95 % CI: 0.73 to 0.98), and 74.9 % (95 % CI: 0.61 to 0.92) at 12 months, respectively.

Minckler and Hill (2009) described the rationales and initial clinical outcomes in studies to date on Glaukos iStent, iScience (canaloplasty), Solx (supra-choroidal shunt), and Trabectome, which are newly developed surgical technologies for the treatment of OAG.  These new approaches to angle surgery have been demonstrated in preliminary case series to safely lower IOP in the mid-teens with far fewer complications than expected with trabeculectomy and without anti-fibrotics.  Trabectome and iStent are relatively non-invasive, aim to improve access of aqueous to collector channels and do not preclude subsequent standard surgery.  Canaloplasty, modified from viscocanalostomy, is thought to improve trans-trabecular flow.  Solx potentially offers an adjustable aqueous outflow into the supra-choroidal space.

In a prospective and non-randomized study, Chakib and colleagues (2010) evaluated the short-term clinical results and complications of viscocanalostomy.  A total of 107 consecutive eyes of 67 patients who underwent viscocanalostomy were analyzed.  The surgeon conducted post-operative care.  The minimal follow-up was 1 year, with a mean follow-up of 13.1 months (range of 12 to 18 months).  The criteria for success were defined as IOP less than 21 mm Hg without treatment.  The mean pre-operative IOP was 28.3 mm Hg while the mean post-operative IOP was 5.4 mm Hg on the first day and 10.2 mm Hg at 13 months.  The rate of patients who had IOP below 21 mm Hg with or without treatment was 98 % at 13 months.  The complete success rate without treatment was 80 % at 13 months.  Seven cases of ocular hypotony lasting more than 1 month were noted.  The authors concluded that viscocanalostomy is a promising procedure because in the short-term it provides good tonometric results in glaucomatous patients without the complications of trabeculectomy.  However, it remains a technique with a learning curve.

Tian and Kaufman (2013) stated that since the inner wall of Schlemm's canal (SC) is directly in contact with the trabecular meshwork (TM) for 360 degrees and the catheter device used in canaloplasty allows viscoelastic to be injected into the entire length of SC, canaloplasty might also be used to perform SC/TM-targeted delivery of transgene vectors for glaucoma gene therapy.  This hypothesized new method for transgene delivery may give the transgene access to the entire inner wall of SC and the whole juxta-canalicular region of the TM and allow the transgene to be expressed in both the TM and SC without affecting the cornea, iris and ciliary body.  The authors concluded that this strategy might have a greater trabecular outflow resistance-decreasing effect than either the genetic or surgical approach alone.

Aktas et al (2014) noted that SC inner wall is adjacent to the juxta-canalicular TM over their entire circumference.  These researchers attempted to transfer reporter and therapeutic genes to these outflow-modulating tissues via canaloplasty surgery in live monkeys.  A standard canaloplasty surgical approach was performed in cynomolgus monkeys using flexible canaloplasty catheters, modified for monkey eyes with a 175-μm outer diameter and an LED-lighted tip.  A 6-0 prolene suture was used for the exact localization of SC.  Trypan blue was injected during catheter withdrawal to document catheter placement within SC and to determine ease of injecting fluid into SC.  Before, during, and after the injection, the position of the catheter and the anatomic details were video-captured with an externally positioned non-contact endoscopic imaging system and 50 mHz ultrasound biomicroscopy (UBM).  A 360-degree catheterization and injection of dye into SC was achieved.  Suture, catheter, and trypan blue were imaged with the endoscope camera system and the catheter was also visualized with UBM.  Trypan blue was seen in the SC over 5 clock hours after a 1 clock-hour insertion of the catheter.  The authors concluded that a modified canaloplasty catheter device might be used for gene delivery to the SC/TM area without circumferential catheterization.  Moreover, they stated that further studies comparing different delivery methods of the vector/transgene into the SC using canaloplasty are needed.

The AAO Preferred Practice Pattern on primary open angle glacoma (AAO, 2015) states that the precise role of canaloplasty in the management of open-angle glaucoma remains to be determined. The AAO states that "The safety and efficacy of canaloplasty alone and combined with phacoemulsification was described in a nonrandomized multicenter clinical trial through 3 years of follow-up [citing Lewis, et al., 2011]. No randomized clinical trial comparing trabeculectomy and canaloplasty exists. A retrospective case series found lower postoperative IOP with trabeculectomy compared with canaloplasty [citing Ayyala, et al, 2011]."

An AAO‘s clinical practice guideline on “Primary open-angle glaucoma” (AAO, 2010) as well as an AAO report on “Novel glaucoma procedures” (Francis et al, 2011) did not mention phacoviscocanalostomy as an therapeutic option.  Furthermore, in an UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2014), viscocanalostomy and phacoviscocanalostomy are not mentioned as therapeutic options.

In a prospective, non-randomized case-series study, Moradian et al (2013) evaluated the safety and effectiveness of viscocanalostomy in the management of medically uncontrollable primary OAG (POAG) in a developing country.  A total of 14 consecutive eyes with medically uncontrollable POAG were subjected to viscocanalostomy.  The main outcome measure was success rate based on the IOP level achieved post-operatively.  The procedure was considered a complete success if IOP was less than 21 mmHg without any anti-glaucoma medication.  Qualified success was defined as IOP of less than 21 mmHg with anti-glaucoma medication.  All patients had a regular follow-up of at least 12 months.  Overall, IOP was reduced from a mean baseline value of 27.9 ± 7.3 mmHg (range of 21 to 40 mmHg) to a mean final value of 16.0 ± 2.7 mmHg (range of 13 to 22 mmHg), which was statistically highly significant (p < 0.005).  The mean number of pre-operative anti-glaucoma medications was 3.0 ± 0.4 (range of 2 to 4), which was reduced significantly (p < 0.0001) to 0.3 ± 0.6 (range of 0 to 2) at the last follow-up visit.  One year post-operatively, complete success was achieved in 71 % and qualified success was observed in 21.4 % of patients, summing up to an overall success rate of 92.4 %. There were no major complications in any of the patients.  The authors concluded that viscocanalostomy could be performed effectively and safely for control of POAG in developing countries.  Moreover, they stated that “A larger number of patients and a longer follow-up period are warranted for the further evaluation of this relatively novel procedure in developing countries.  In addition, comparing the future surgical cases of the same surgeon would show the learning curve of viscocanalostomy more precisely.  However, we believe that the high success rate and low complication rate in these initial 14 cases are highly encouraging to suggest popularization of non-penetrating glaucoma procedures in developing countries”.

In a Cochrane review, Eldaly and colleagues (2014) compared the effectiveness of non-penetrating trabecular surgery with conventional trabeculectomy in people with glaucoma.  These investigators searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to September 2013), EMBASE (January 1980 to September 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to September 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en).  They did not use any date or language restrictions in the electronic searches for trials.  They last searched the electronic databases on September 27, 2013.  This review included relevant RCTs and quasi-RCTs on participants undergoing standard trabeculectomy for OAG compared to non-penetrating surgery, specifically viscocanalostomy or deep sclerectomy, with or without adjunctive measures.  Two review authors independently reviewed the titles and abstracts of the search results.  They obtained full copies of all potentially eligible studies and assessed each one according to the definitions in the “Criteria for considering studies” section of this review.  They used standard methodological procedures expected by The Cochrane Collaboration.  These researchers included 5 studies with a total of 311 eyes (247 participants) of which 133 eyes (participants) were quasi-randomized.  A total of 160 eyes that had trabeculectomy were compared to 151 eyes that had non-penetrating glaucoma surgery (of which 101 eyes had deep sclerectomy and 50 eyes had viscocanalostomy).  The CI for the odds ratio (OR) of success (defined as achieving target eye pressure without eye drops) does not exclude a beneficial effect of either deep sclerectomy or trabeculectomy (OR 0.98, 95 % CI: 0.51 to 1.88).  The odds of success in viscocanalostomy participants was lower than in trabeculectomy participants (OR 0.33, 95 % CI: 0.13 to 0.81).  These investigators did not combine the different types of non-penetrating surgery because there was evidence of a subgroup difference when examining total success.  The OR for achieving target eye pressure with or without eye drops was imprecise and was compatible with a beneficial effect of either trabeculectomy or non-penetrating filtration surgery (NPFS) (OR 0.79, 95 % CI: 0.35 to 1.79).  Operative adjuvants were used in both treatment groups; more commonly in the NPFS group compared to the trabeculectomy group, but no clear effect of their use could be determined.  Although the studies were too small to provide definitive evidence regarding the relative safety of the surgical procedures, these researchers noted that there were relatively fewer complications with non-filtering surgery compared to trabeculectomy (17 % and 65 %, respectively).  Cataract was more commonly reported in the trabeculectomy studies.  None of the 5 trials used quality of life measure questionnaires.  The methodological quality of the studies was not good.  Most studies were at high risk of bias in at least one domain and for many, there was lack of certainty due to incomplete reporting.  Adequate sequence generation was noted only in 1 study.  Similarly, only 2 studies avoided detection bias.  These investigators detected incomplete outcome data in 3 of the included studies.  The authors concluded that this review provided some limited evidence that control of IOP is better with trabeculectomy than viscocanalostomy.  For deep sclerectomy, they could not draw any useful conclusions.  This may reflect surgical difficulties in performing non-penetrating procedures and the need for surgical experience.  This review has highlighted the lack of use of quality of life outcomes and the need for higher methodological quality RCTs to address these issues.  Since it is unlikely that better IOP control will be offered by NPFS, but that these techniques offer potential gains for patients in terms of quality of life, the authors felt that such a trial is likely to be of a non-inferiority design with quality of life measures.

Ghate and Wang (2015) stated that primary congenital glaucoma (PCG) manifests within the first few years of a child's life and is not associated with any other systemic or ocular abnormalities.  Primary congenital glaucoma results in considerable morbidity even in developed countries.  Several surgical techniques for treating this condition, and lowering the IOP associated with it, have been described.  These investigators compared the safety and effectiveness of different surgical techniques for PCG.  They searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en).  They did not use any date or language restrictions in the electronic searches for trials.  They last searched the electronic databases on June 23, 2014.  These researchers included all randomized and quasi-randomized trials in which different types of surgical interventions were compared in children less than 5 years of age with PCG.  The authors used standard methodological procedures specified by The Cochrane Collaboration.  A total of 6 trials (4 randomized and 2 quasi-randomized) with 102 eyes in 61 children were included in this analysis.  Two trials were conducted in the USA and 1 trial each in Egypt, Israel, Lebanon and Saudi Arabia.  All trials included children aged younger than 1 year when diagnosed with PCG, and followed them for periods ranging from 6 months to 5 years.  No 2 trials compared the same pair of surgical interventions, so these investigators did not perform any meta-analysis.  One trial compared trabeculotomy versus goniotomy; a 2nd trial compared combined trabeculectomy-trabeculotomy with mitomycin C versus trabeculectomy-trabeculotomy with mitomycin C and deep sclerectomy; a 3rd trial compared combined trabeculotomy-trabeculectomy versus trabeculotomy; a 4th trial compared 1 goniotomy versus 2 goniotomies; a 5th trial compared trabeculotomy versus viscocanalostomy; and the 6th trial compared surgical goniotomy versus neodymium-YAG laser goniotomy.  For IOP change and surgical success (defined by IOP achieved), none of the trials reported a difference between pairs of surgical techniques.  However, due to the limited sample size for all trials (average of 10 children per trial), the evidence as to whether a particular surgical technique is effective and which surgical technique is better still remains uncertain.  Adverse events, such as choroidal detachment, shallow anterior chamber and hyphema, were reported from 4 trials.  None of the trials reported quality of life or economic data.  These trials were neither designed nor reported well overall.  Two trials were quasi-randomized trials and judged to have high risk of selection bias; 4 trials were at unclear or high risk for performance bias and detection bias; and these researchers judged 1 trial to have high risk of attrition bias due to high proportions of losses to follow-up.  Due to poor study design and reporting, the reliability and applicability of evidence remain unclear.  The authors concluded that no conclusions could be drawn from the trials included in this review due to paucity of data.  They stated that more research is needed to determine which of the many surgeries performed for PCG are effective.

Tan and colleagues (2016) stated that childhood glaucoma is known to be one of the most challenging conditions to manage. Surgical management is more complicated than in adults because of differences in anatomy from adults along with variations in anatomy caused by congenital and developmental anomalies, wide-ranging pathogenetic mechanisms, a more aggressive healing response, and a less predictable post-operative course.  Challenges in post-operative examination and management in less co-operative children and the longer life expectancies preempting the need for future surgeries and re-interventions are also contributing factors.  Angle surgery is usually the 1st-line treatment in the surgical management of primary congenital glaucoma because it has a relatively good success rate with a low complication rate.  After failed angle surgery or in cases of secondary pediatric glaucoma, options such as trabeculectomy, glaucoma drainage devices, or cyclodestructive procedures can be considered, depending on several factors such as the type of glaucoma, age of the patient, and the severity and prognosis of the disease.  Various combinations of these techniques have also been studied, in particular combined trabeculotomy-trabeculectomy, which has been shown to be successful in patients with moderate-to-advanced disease.  Newer non-penetrating techniques, such as viscocanalostomy and deep sclerectomy, have been reported in some studies with variable results.  The authors concluded that further studies are needed to evaluate these newer surgical techniques, including the use of modern minimally invasive glaucoma surgeries, in this special and diverse group of young patients.

The current UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2016) still does not mention viscocanalostomy and phacoviscocanalostomy as therapeutic options.

Canaloplasty for the Treatment of Uveitic Glaucoma

Lommatzsch and colleagues (2016) noted that glaucoma is a common vision-threatening complication of uveitis.  In a pilot study, these investigators examined the outcome of canaloplasty in patients with chronic uveitis and uncontrolled secondary glaucoma.  This was a retrospective study of 12 patients with medically uncontrolled secondary glaucoma who underwent canaloplasty (14 treated eyes), with follow-up of greater than or equal to 24 months.  The primary outcome measure was complete and qualified (requirement for anti-glaucomatous medication) surgical success rates, as determined by a reduction in IOP and the need for anti-glaucomatous medication.  Secondary outcome measures were uveitis activity, best-corrected visual acuity (BCVA), vision-threatening complications, and secondary glaucoma surgery.  Canaloplasty resulted in a significant IOP reduction, from a mean pre-operative baseline level of 27.1 ± 12.3 mmHg to a mean of 14.5 ± 4.3 mmHg (p = 0.01) at 24 months.  Complete success (limit of 15 mmHg) was achieved in 6 patients and qualified success in 1 patient.  However, failure was noted in 5 patients, 2 of whom required additional glaucoma surgery.  Topical anti-glaucomatous medications were reduced from 2.7 ± 1.2 (mean ± SD) at baseline to 0.6 ± 1.2 at 24 months (p = 0.007).  Uveitis activity did not increase after surgery; BCVA was not reduced; cataract progressed in 2 patients.  The authors concluded that at 2-year follow-up, overall success rate was 58 % (IOP less than or equal to 15 with or without medication), and surgery failed in 5 eyes, 2 eyes requiring additional glaucoma surgery.  No harmful complications or worsening of uveitis activity were noted.  These preliminary findings from a small (n= 12 patients) pilot study need to be validated by well-designed studies.

Canaloplasty for the Treatment of Normal-Tension Glaucoma

The Academy of Ophthalmology’s Preferred Practice Pattern on “Primary open-angle glaucoma” (AAO, 2016) stated that there are benefits to lowering IOP even in persons with normal-tension glaucoma.

Viscocanalostomy / Phacoviscocanalostomy for the Treatment of Glaucoma

In a retrospective study, Qian and colleagues (2017) evaluated the long-term outcome of viscocanalostomy combined with trabeculotomy (VCT) and mitomycin C in the treatment of PCG.  A total of 42 eyes of 26 patients with PCG were enrolled; IOP, corneal diameter (mm) and cup/disc (C/D) were measured before and after the surgery respectively.  Follow-up period was 30 months.  The mean pre-operative IOP was 30.6 ± 7.35 mm Hg.  Of the 42 eyes, 2 eyes were required conversion to trabeculectomy for the absence of Schlemm's canal.  Of remained 40 eyes, 38 eyes (95 %) achieved successful IOP control.  The average post-operative IOP was 11.69 ± 4.18 mm Hg at 12 months.  The mean reduction was 18.91 mm Hg (p < 0.0001); 18  (75 %) eyes presented a reduction in corneal diameter, and 25 (62.5 %) eyes presented a C/D ratio reversal after the surgery.  There was no serious complication in any patients over the follow-up period.  The authors concluded that the findings of this study demonstrated that VCT was safe and effective in controlling infantile glaucoma, and it could be an alternative choice for infantile glaucoma procedure in the future although controlled studies with large subject numbers and long follow-up period are needed.

Ho and associates (2017) evaluated the efficacy of viscocanalostomy/phacoviscocanalostomy (VC/PVC) in lowering IOP in patients with normal tension glaucoma (NTG).  These investigators carried out a retrospective electronic database review of patients who underwent VC/PVC for NTG between December 2009 and November 2011 at Stanley eye unit in Abergele Hospital.  Goldmann applanation tonometry (GAT) was used for all IOP measurements, which were taken at the time of listing for surgery and at 1 day, 1 week, 1 month, then 3-monthly up to 1 year, then half-yearly up to 3 years post-operatively.  Statistical analysis was performed using unpaired t-test.  A p value of < 0.05 was accepted as the level of significance.  Operations were performed on 94 eyes from 67 patients over the study period.  The mean age at the time of surgery was 76.4 years.  Pre-operative IOP was 17.75 ± 2.19 mmHg (range of 12 to 21 mmHg); 3 year follow-up showed a mean IOP of 13.41 ± 2.22 mmHg (range of 8 to 18 mmHg).  By year 3, a total of 17 patients needed laser goniopuncture and 25 patients needed anti-glaucoma drops; IOP was reduced by 24.4 % at 3 years post-surgery, which was statistically significant (p < 0.0001).  The authors concluded that from these findings, which showed a 24.5 % reduction in IOP at 3 years with 12 % complication rate, they proposed that a logical surgical management for NTG patients would be viscocanalostomy, thereby keeping trabeculectomy as an alternative.

The authors stated that this study had several drawbacks.  First, it was a retrospective study.  In addition the patients in this study were from a different population, without any control group compared to other studies.  This might make interpretation of these findings with other study populations difficult.  Post-operative evaluation including tonometry was not masked and therefore subject to observer bias.  Second, this  study did not consider analysis of phakic versus pseudophakic eyes, as study participants included only 6 phakic eyes within the VC subgroup, compared to 88 pseudophakic eyes either from previous cataract operations or as a result of combined PVC surgeries.  These researchers considered the number of phakic eyes to be too low to draw any statistical conclusions with sufficient power.  Third, VA was not analyzed in this study.  Lastly, visual field analysis in previous papers was performed using various methods, making it difficult to directly compare the visual field analysis from this study.

Viscocanalostomy and Combined Phacoemulsification with Viscocanalostomy in the Treatment of Uveitic Glaucoma

El Salloukh and colleagues (2021) noted that uveitic glaucoma commonly leads to a more intense optic nerve damage than other types of glaucoma, resulting in glaucomatous optic nerves and visual field defects.  Anterior uveitis is the most commonly associated risk factor.  Surgical intervention is usually indicated when all medical treatment has failed.  In a retrospective, case-series study, these investigators reported 5-year results for 16 eyes of uveitic glaucoma managed with viscocanalostomy (VC)/phaco-viscocanalostomy (PVC).  All patients were managed surgically with either VC or PVC.  Outcomes evaluated included IOP measurement pre-listing, on day 1, year 1 to year 5.  Complete success rate was defined as achieving an IOP lower than 21 mmHg or reduced by 30 % without medications, and qualified success was achieved when IOP was lower than 21 mmHg or a reduction in IOP of 30 % with topical medical therapy ± laser gonio-puncture (LGP).  If further surgeries were required to reduce IOP due to glaucoma progression, then they were classified as a failure.  A total of 16 patients with uveitic glaucoma were reviewed.  Complete success was observed in 75 % of patients at year 1, 50 % of patients at year 3 and 19 % of patients in year 5.  Conversely, qualified success was achieved in 94 % of patients at year 1, 86 % of patients at year 3 and 75 % of patients at year 5.  In the group of patients requiring further surgery, 50 % of patients had previous surgeries, including cataract surgery, trabeculectomy and viscocanalostomy.  There was a mean number of 4 pre-operative drops before their primary surgery and a mean drop in eye medications of 1.1 at 5 years follow-up.  Success rates were prognostically linked to lower mean number of interventions and lower percentage of previous surgeries.  The authors concluded that there remains a significant paucity of information in the utilization of PVC in uveitic glaucoma.  The advantage of NPGS includes the lack of entry into the anterior chamber and the avoidance of an iridectomy that may reduce intra-ocular inflammation and post-operative complications.  This study showed that non-penetrating surgery was successful in treating advanced uveitic glaucoma.

The authors stated that there are several limiting factors in this study.  This was a retrospective case-series study with limited sample size (n = 16 eyes) and the included eyes were heterogeneous based on type of uveitis, type of procedure and lens status.  None of the subjects was on immune-modulating medication and this may have affected the success rate.  Furthermore, of relevance was that these investigators only had idiopathic uveitis and Fuch’s heterechromic cyclitis (FHC) and hence a direct comparison with other studies (with different uveitic etiology) was not possible.  The limited sample size, heterogeneous subjects further reduced the possibility for analytical approach to the data.  In addition, these findings were of surgery in a subset of patient with mild form of uveitis and could not be generalized to other types of uveitis.

Corticosteroid-Induced Glaucoma

Brusini and colleagues (2018) presented the mid-term results of canaloplasty in a small cohort of patients with corticosteroid-induced glaucoma (CIG).  A total of 9 eyes from 7 patients with various types of CIG in maximum medical therapy underwent canaloplasty.  Patients underwent complete ophthalmic examination every 6 months.  Success was defined as: post-operative IOP of less than or equal to 21 mmHg and less than or equal to 16 mmHg without ("complete success"), and with/without medical treatment ("qualified success").  The IOP reduction had to be greater than or equal to 20.  The number of medications before and after surgery was considered.  The follow-up mean period was 32.7 ± 20.8 months (range of 14 to 72 months).  The pre-operative mean IOP was 30.7 ± 7.2 mmHg (range of 24 to 45).  The mean IOP at 6 and 12-month follow-up was 13.1 ± 2.6 mmHg, and 13.7 ± 1.9 mmHg, respectively.  Qualified and complete success at 6 and 12 months was 100 % for both of the 2 definitions.  The number of medications used pre-operatively and at the 12-month follow-up was 4.3 ± 0.7, and 0.2 ± 1.0, respectively.  No serious complication was observed.  The authors concluded that the mid-term results of canaloplasty in patients with CIG appeared to be very promising.  They stated that canaloplasty should be considered as a possible alternative to filtering surgery in this form of glaucoma, when medical therapy is not sufficient to maintain the IOP within reasonable limits.  Moreover, they stated that the study is currently still underway.  New patients with CIG that fit the inclusion criteria are being added and follow-up data of existing patients are being constantly updated to provide long-term results and a larger cohort for the future study.  Regarding these patients, multi-centric randomized studies with a larger population, where canaloplasty is compared to gold standard surgery (trabeculectomy), are needed to draw more definite and robust conclusions.

The authors stated that even the results obtained were very promising, it should be remembered that this was a non-randomized study with a small sample of patients (n= 9 eyes) without a control group.  Another drawback of this study was that both eyes of 2 patients had been considered.  Even if this could be incorrect from a statistical point of view, considering the small number of patients treated, these researchers decided to describe all cases they treated with this surgical procedure.

Stegmann Canal Expander for Canaloplasty

In a non-comparative, prospective study, Grieshaber and colleagues (2017) examined longer-term post-surgical safety and efficacy of a new expander for Schlemm's canal (SC).  A total of 42 White patients with medically uncontrolled POAG underwent primary canaloplasty with greater than 2-year follow-up.  The bleb-independent procedure comprised catheter-assisted canaloplasty and implantation of 2 Stegmann Canal Expanders to maintain trabecular distension and canal patency over 180°; IOP, glaucoma medication use and complications were assessed.  Mean IOP was 26.8 ± 5.6 mmHg pre-surgery, 12.8 ± 1.5 mmHg at 6 months, 13.2 ± 1.2 mmHg at 12 months and 13.3 ± 2.5 mmHg at 24 months (p < 0.001).  Rate of complete success, defined as IOP less than or equal to 21, less than or equal to 18, and less than or equal to 16 mmHg and a ≥ 30 % IOP reduction, was 85 % (95 % CI: 0.76 to 0.95), 85 % (0.76 to 0.95) and 82 % (0.70 to 0.96) at 12 months and 83 % (0.73 to 0.94), 80 % (0.70 to 0.92) and 80 % (0.70 to 0.92) at 24 months.  Pre-operative factors were not significant predictors of less than or equal to 16 mmHg IOP reduction: IOP (hazard ratio [HR]: 0.68; 95 % CI: 0.44 to 1.04; p = 0.08), mean visual defect (1.06; 0.90 to 1.20; p = 0.47), number of medications (0.59; 0.17 to 2.14; p = 0.42) and age (0.96; 0.87 to 1.13; p = 0.41).  Number of medications dropped from 2.8 ± 0.4 pre-surgery to 0.2 ± 0.5 post-surgery (p < 0.001).  Mean pre-operative BCVA was 0.19 ± SD 0.21 (range of 0 to 1.6), and logMAR was similar to 0.23 ± 0.16 (range of 0 to 1.6; p = 0.42) after a mean follow-up of 27.4 months.  Complications included peripheral Descemet's membrane detachment (7.2 %) and trimming of the expander (4.7 %) during surgery, and transient microhyphema (23.8 %) and IOP elevation (7.2 %) post-surgery.  The authors concluded that canaloplasty with the Stegmann Canal Expander was a safe and effective procedure to reduce IOP in White patients with moderate-to-advanced POAG; however, comparative, randomized trials are needed to draw final conclusions.

The authors stated that in spite of the promising findings, the results of this study need to be interpreted with caution due to study limitations.  First, the study design was un-masked and non‐comparative; thus, it lacked a control group, namely standard canaloplasty.  Second, the Stegmann Canal Expander has only been evaluated in White patients with POAG undergoing primary surgery, thus, the results could not be extrapolated to patients of other ethnicity, to eyes with other types of glaucoma, or to eyes with previous surgery, which could have impeded cannulation of SC and implantation of the device.  Furthermore, it should be noted that the surgeons in this study had many years of experience with non‐penetrating glaucoma surgery, and thus, the results did not include the long learning curve related to the dissection of the scleral flaps and preparation of the Descemet's membrane window.

Grieshaber (2018) stated that the concept of canaloplasty is to increase aqueous egress through all structures that control the aqueous outflow, such as the trabecular meshwork, SC, and collector channels, by visco-modulation and by placing of a suture stent into the canal.  Clinical studies showed canaloplasty to be safe and efficient in lowering the IOP; however, proper knotting of the tensioning suture is technically challenging and even impossible if circumferential cannulation cannot be achieved.  Furthermore, protrusion of the suture stent is a potential lifelong risk.  The specific design of the Stegmann Canal Expander allows a permanent expansion of the canal and distension of the trabecular meshwork; 2 expanders are implanted on either side of the surgically created ostium of SC to treat half of the circumferential outflow system.  The author described the technique step-by-step, provided the clinician with surgical pearls, and highlighted the management of adverse events (AEs).  This investigator noted that technically, implantation of the Stegmann Canal Expander was simple and did not require a long learning curve, compared to placing and knotting a tensioning suture.  Most issues were related to the 2-flap dissection technique (deep sclerectomy technique) and not to implantation of the Stegmann Canal Expander; and IOP reduction without medications to the low teens could be achieved.  The authors concluded that Stegmann Canal Expander is a novel micro-device that has the potential to make canaloplasty a simplified, more controlled, and reproducible surgical procedure.

Furthermore, an UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2019) does not mention canal expander as a management tool.

Combined Phacoemulsification and Viscocanalostomy with Ologen Implant

In a prospective, interventional, randomized clinical study, Gad and colleagues (2019) examined the efficacy of the biodegradable collagen implant Ologen as an adjuvant in phaco-viscocanalostomy in patients with co-existing cataract and POAG.  This trial entailed patients with co-existing cataract and glaucoma who were randomized to receive either phaco-viscocanalostomy (Phacovisco group) (39 eyes) or phaco-viscocanalostomy with Ologen implant (OloPhacovisco group) (40 eyes).  Follow-up period was 2 years; Nd:YAG laser gonio-puncture was performed in cases where the IOP was elevated above 21 mmHg after discontinuation of corticosteroid eye drops at any follow-up visit.  No significant operative or post-operative complications (other than failure) were encountered in either group.  At 2 years follow-up, the mean IOP level was statistically significantly decreased in the OloPhacovisco group (p = 0.02) and complete success occurred in 23 eyes (59.0 %) in the Phacovisco group and in 32 eyes (80.0 %) in the OloPhacovisco group.  There was a statistically significant higher success rate regarding complete success in patients that received Ologen implant (p = 0.04).  The authors concluded that Ologen implant improved the success rate of phaco-viscocanalostomy.  Moreover, these researchers stated that larger studies with longer follow-up periods are needed to confirm the safety and efficacy of this device in viscocanalostomy.  The main drawbacks of this study were the relatively small sample size (40 eyes in the OloPhacovisco group) and short follow-up period (2 years).

Ab Interno Canaloplasty (ABiC)

In a retrospective, cohort outcome study, Davids and colleagues (2019) examined if the ab interno canaloplasty (ABiC) is a reasonable minimally invasive method to significantly reduce the IOP and number of anti-glaucomatous medications over a certain period of time in adults with POAG.  A total of 36 eyes of 28 POAG patients (mean age of 74.8 ± 9.3 years) with an IOP above target pressure were included; ABiC was performed in all subjects as sole procedure in pseudophakic eyes (n = 20) or in combination with cataract surgery in phakic eyes (n = 16); IOP and the number of anti-glaucomatous medications were evaluated pre-operatively, day 1, week 6, month 3, month 6, and month 12.  IOP decreased from 19.8 ± 4.1 to 13.8 ± 3 mmHg at 12 months follow-up (n = 21, p < 0.001).  The IOP reduction showed significant results at all time-points (1 day p < 0.001; 6 weeks p < 0.001; 3 months p < 0.001; 6 months p = 0.001; and 12 months p < 0.001).  Glaucoma therapy was stabilized at 2.1 ± 1.6 number of anti-glaucomatous medications after 12 months post-operatively.  There was no significant difference in the number of anti-glaucomatous medication at 12 months follow-up (p = 1.0).  No major peri-operative complications were reported.  The authors concluded that the ABiC effectively lowered the IOP in POAG in the short-term follow-up of 12 months; however, a reduction of glaucoma therapy could not be attained and should be discussed with the patients before surgery.

Canaloplasty for the Teatment of Pseudoexfoliation Glaucoma

Hasanov and Kasimov (2018) examined the safety and efficacy of phaco-canaloplasty in patients with concomitant advanced pseudoexfoliation glaucoma and cataract.  The study included 56 patients (57 eyes) who underwent phacoanaloplasty guided by Glaucolight microcatheter.  All patients were followed up for 48 months.  Visual acuity (VA), changes of intra-ocular pressure (IOP), use of glaucoma medications, incidence of complications, as well as post-surgical interventions were examined.  Mean pre-operative IOP decreased significantly from 29.8 mmHg (15.8 to 61.6) with a mean of 1.92 (0 to 3) glaucoma drops to 12.9 mmHg (11.0 to 19.6) with a mean of 0.12 (0 to 3) drops, respectively 48 months after phacocanaloplasty.  Mean VA increased from pre-operative 0.15 (0.01 to 0.8) to 0.6 (0.01 to 1.2).  The most frequent complications included intra-operative perforation of Descemet's membrane (4 eyes, 7 %) and hyphema (37 eyes, 65 %), IOP spikes (4 eyes, 7 %) and inflammation (4 eyes, 7 %) in the early post-operative period.  The authors concluded that phacocanaloplasty in eyes with concomitant advanced pseudoexfoliation glaucoma and cataract re-established the natural outflow system and led to significant IOP reduction with minimal risk of intra- and post-operative complications.

Gabai et al (2019) carried out a meta-analysis on the safety and efficacy of trabeculectomy (TE) and non-penetrating glaucoma surgery (NPGS) techniques in patients with primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma, pigmentary glaucoma, and normal-tension glaucoma.  All studies were identified by searching electronic sources (PubMed, Medline, Scopus, and Embase) until February 5, 2018.  Primary outcome was mean IOP reduction at 6, 12, and 24 months.  Complications, number of anti-glaucomatous medications, and visual outcomes were also evaluated.  A total of 21 studies were included; 10 studies compared TE with deep sclerectomy (DS), 5 with viscocanalostomy (VC), 1 study with both DS and VC, and 5 with canaloplasty (CP).  TE was superior to DS, VC, and CP in reducing IOP at 6 and 12 months, and to DS at 24 months.  When comparing TE to VC and to CP at 24 months, there was no significant difference in IOP reduction.  Hypotony, choroidals, anterior chamber shallowing or flattening, and cataract formation or progression were more associated with TE than with NPGSs.  TE was more effective in reducing anti-glaucomatous medications than VC and CP.  The authors concluded that TE was more effective in reducing IOP; and it presented a higher risk of complications as compared with NPGS, except for hyphema.

Kodomskoi et al (2019) noted that significant IOP reduction was achieved using a novel suture-probe canaloplasty (SPCP) procedure in patients with glaucoma.  The effect and low rate of surgical complications were comparable with those of iTrack canaloplasty.  Ab externo canaloplasty using the iTrack microcatheter has been established as a safe surgical procedure to treat OAG.  These researchers described the results of a novel technique using a cost-efficient suture-probe as an alternative to iTrack canaloplasty and presented 12-month follow-up results.  SPCP was carried out on 50 eyes of 50 patients with POAG, pseudoexfoliation glaucoma, and steroid-induced glaucoma.  The mean ± SD pre-operative IOP was 21.9 ± 7.0 mm Hg.  A suture-probe was used to dilate Schlemm canal and to place a trabecular tensioning suture.  Post-operative results were noted and statistically analyzed on the day of discharge from the clinic, and at 1.5, 3, 6, and 12 months of follow-up.  In all eyes, the mean post-operative IOP 12 months after SPCP was 13.7 ± 3.0 mm Hg.  The number of medications decreased from 2.8 ± 0.9 to 0.1 ± 0.4, and VA was 0.3 ± 0.3 logMAR.  Post-operative course and complications included: hyphema of greater than 1 mm (2 %); micro-hyphema (4 %); bleb leakage (2 %); bleb suture (2 %); laser gonio-puncture (18 %); laser suture lysis (4% ); scleral flap lifting (4 %); and iris incarceration following laser gonio-puncture (4 %).  The authors concluded that SPCP was an inexpensive procedure that could achieve significant IOP reduction in patients with glaucoma.  The IOP-lowering effect and low rate of surgical complications were very similar to those of iTrack canaloplasty.

Seuthe et al (2021) examined the long-term safety and efficacy of the modified canaloplasty technique with additional suprachoroidal drainage in patients with pseudoexfoliation glaucoma.  This retrospective clinical trial included 131 patients with pseudoexfoliation glaucoma who underwent canaloplasty with suprachoroidal drainage (scD).  A total of 111 of 131 patients underwent the follow-up examination after 48 months.  Primary endpoints were the pressure-lowering and drug-sparing effect as well as the success rates.  Secondary endpoints were intra- and post-operative complications and the occurrence of secondary surgical interventions.  The IOP was reduced by 45.8 % after 12 months (from baseline 23.4 ± 5.1 mmHg to 12.7 ± 2.2 mmHg) and by 45.1 % after 4 years (12.8 ± 2.2 mmHg) (p < .001).  The mean number of IOP-lowering medication decreased significantly from 3.4 at baseline to 0.6 after 12 months and to 1.0 after 4 years.  The IOP-reducing effect was even stronger in those cases in whom canaloplasty+ scD was combined with cataract surgery (49.4 % after 12 months and 47.6 % after 4 years).  No serious complications were observed.  The authors concluded that the modified surgery technique of canaloplasty with suprachoroidal drainage was a safe and effective way of reducing IOP in patients with pseudoexfoliation glaucoma.

Furthermore, an UpToDate review on “Open-angle glaucoma: Epidemiology, clinical presentation, and diagnosis” (Jacobs, 2021) states that “Other possible risk factors for developing open-angle glaucoma include myopia, pseudoexfoliation, low diastolic perfusion pressure, cardiovascular disease, a history of prior vitreoretinal surgery, and hypothyroidism”.

Canaloplasty and Trabeculotomy Ab Interno with the OMNI System Combined with Cataract Surgery for the Treatment of POAG

In a retrospective, single-arm, multi-center study, Hirsch and colleagues (2021) provided safety and effectiveness outcomes 12 months post-surgically for sequential canaloplasty and trabeculotomy with the OMNI System combined with cataract surgery in mild-to-moderate OAG.  The trial was carried out in 11 ophthalmology practices and surgery centers located in 8 states (AL, AR, CA, KS, LA, MO, NY, TX).  A total of 12 surgeons contributed 81 patients meeting eligibility criteria: OAG, 12-month follow-up, medicated IOP of less than or equal to 36 mmHg on less than or equal to 4 medications pre-operatively.  Analysis stratified by baseline (BL) IOP; greater than 18 mmHg (group 1), less than or equal to 18 mmHg (Group 2).  Success defined as proportion with greater than or equal to 20 % reduction in IOP, or IOP between 6 and 18 mmHg (inclusive) AND on the same or fewer medications without secondary surgical intervention (SSI).  Other endpoints included mean IOP and medications at 12 months; and safety outcomes included BCVA and AEs.  Primary success was met by 79 % (Group 1) and 81 % (Group 2).  Mean IOP was reduced in Group 1 (21.9 to 15.1 mmHg, p < 0.0001), and remained controlled in Group 2 (14.1 to 13.4 mmHg, p = 0.3177).  Medications went from 2.0 ± 1.3 to 1.1 ± 1.1 (Group 1) and from 1.6 ± 1.3 to 0.9 ± 1.2 (Group 2); AEs were typical for cataract or angle surgery: mild inflammation (11 %), IOP spikes (5 %), hyphema (4 %); and 4 patients (5 %) required an SSI.  The authors concluded that OMNI system provided effective IOP reduction, sustained IOP control, and meaningful medication reduction for up to 12 months post-operative.  The OMNI System provided the ability to perform a circumferential viscodilation and ab interno trabeculotomy.  This newly introduced device showed promising preliminary results for the management of moderate and advanced glaucoma; however, limited data are currently available regarding its safety and efficacy because of the short time this device has been marketed.

In a retrospective, single-center, consecutive, case-series study, Hughes and Traynor (2020) reported treatment outcomes of ab interno canaloplasty using the Visco360 and Omni system devices as a standalone procedure or combined with cataract surgery in patients with open-angle glaucoma (OAG).  A total of 89 eyes of 64 patients aged 43 to 91 with OAG treated with ab interno canaloplasty between January 2018 and September 2019 were included in this trial.  Eyes with previous incisional glaucoma surgery and eyes with less than 90 degrees of viscodilation were excluded.  Patients underwent ab interno canaloplasty as a stand-alone procedure or in conjunction with cataract surgery.  Ab interno canaloplasty was carried out with either the Visco360 or Omni System devices.  Treatment consisted of viscodilation without trabeculotomy.  Primary outcome measures were mean IOP and mean number of glaucoma medications.  Additional analysis included the impact of degrees of treatment on health outcomes.  Pre-operative mean IOP was 24.5 ± 8.3; the number of pre-operative glaucoma medications was 2.5 ± 1.3.  At 18 months post-operative, the mean IOP was reduced 36 % to 15.8 ± 2.5 (p < 0.001) and glaucoma medications were reduced 32 % to 1.7 ± 1.5 (p < 0.05).  Higher pre-operative IOP was significantly correlated with increased IOP lowering.  Reduction of mean IOP and medications were not significantly different between standalone ab interno canaloplasty versus cataract surgery/ab interno canaloplasty.  Reduction of mean IOP and medications were not significantly different between patients with 180 degrees of treatment vs 360 degrees of treatment.  The authors concluded that ab interno canaloplasty reduced IOP and glaucoma medication use in patients with OAG whether as a standalone surgery or in combination with cataract surgery.

The authors stated that study limitations included the relatively small number of standalone surgery eyes.  Nevertheless, the standard deviation at 18 months for this group was similar to that for the overall group providing some confidence in the point estimate for the mean.  With 72 eyes in the combined with cataract group, the results were reasonably robust.  This study was also limited by the weaknesses inherent to retrospective studies including selection bias and variable follow-up.  To mitigate against this potential bias, all eligible patients were included with minimal exclusion criteria.  Both eyes from a given patient were included in the analysis when each eye met the eligibility criteria; thus, complete independence of all variates was not satisfied.  The consequence of this was potential under-estimation of variability in the findings; however, the measured standard deviation for the IOP at baseline was greater than generally observed in published studies (e.g., 3 to 4 mmHg) arguing against such bias.  Nevertheless, this potential bias should be considered when interpreting the results.  In the authors’ view, the increased number of surgical cases and the consequent greater likelihood of revealing infrequent safety issues more than balanced this weakness.  The study did not attempt to explain how ab interno canaloplasty reduced IOP; and there was no further investigation to understand why some eyes were not able to receive a full circum-navigation of 360 degrees.

In a prospective, institution review board (IRB)-approved, multi-center study, Pyfer et al (2021) analyzed diurnal IOP data (9 AM, 12 PM, and 4 PM) from a prospective 12-month trial of the OMNI Surgical System in OAG)patients with the aim of examining the effect of MIGS surgery on the amplitude of the diurnal IOP profile pre- and post-operatively.  A total of 15 ophthalmology practices and surgery centers located in 14 states in the U.S.  Subjects included patients treated with canaloplasty (360°) and trabeculotomy (180°).  Patients had cataract and mild-to-moderate OAG with IOP of less than or equal to 33 mmHg on 0 to 4 hypotensive medications.  Post-hoc analysis of diurnal IOP data from the multi-center GEMINI study.  Analysis included comparison of IOP pre-operatively and at month 12 for each of the diurnal time-points, 9 AM, 12 PM, and 4 PM, change in magnitude of spread between the maximum IOP and minimum IOP for each patient and the proportions of patients pre-operatively and at month 12 with IOPs at or below 25, 21, 18, and 15 mmHg, average variability (standard deviation [SD] of the 9 AM, 12 PM, and 4 PM IOP) pre-operatively and at month 12.  A total of 128 patients included in this analysis.  IOP at each diurnal timepoint was significantly lower post-operatively (p < 0.0001).  The difference between highest and lowest IOP measurement for each patient averaged 2.8 mmHg pre-operatively (SD 2.4, MAX 14, MIN 0) and 1.8 mmHg (SD 1.7, MAX 10, MIN 0) month 12 (p < 0.00001).  The proportion with IOP less than or equal to 25, 21, 18, and 15 mmHg increased 75 % to 97 %, 27 % to 88 %, 1 % to 79 %, and less than 1 % to 56 %, respectively.  The average variability was greater at all time-points pre-operatively (p < 0.0001).  The authors concluded that the findings of this study demonstrated that eyes with OAG could benefit from an overall decreased IOP and degree of IOP fluctuations for as long as 12 months after surgical treatment with canaloplasty and trabeculotomy.  Moreover, these researchers stated that further study with a greater sample size and longer follow-up are needed and ongoing.  Study using other minimally (or micro) invasive glaucoma surgery (MIGS) procedures to determine the generalizability of these results are also needed.

The authors stated that this study had several drawbacks.  First, analysis of fluctuation was not an a priori objective of the GEMINI study; however, these researchers had employed appropriate statistical analyses including testing for normality and using distribution-free methods where appropriate, controlling for multiplicity using Bonferroni correction, and limiting the data interrogation to focus on intra-patient IOP variability.  Second, this study did not address progression; the GEMINI study was not designed to assess progression.  Automated perimetry was performed at pre-operative baseline and at month 12 primarily for eligibility and safety reasons; however, there were no AEs for worsening of visual field mean deviation.  Third, there was not an untreated control group.  Including a “no treatment” or placebo control is problematic for ethical reasons in a 12-month long study such as GEMINI where patients have a progressive and potentially blinding disease.  However, the analysis did compare pre-operative with post-operative IOP data for the same patients; effectively each patient serving as their own control.  Finally, these findings suggested that MIGS could be effective in controlling IOP fluctuations; however, the data were restricted to eyes treated with canaloplasty and trabeculotomy using the OMNI Surgical System.  These investigators did not know if these findings could be generalized to other MIGS procedures and implants.

In a prospective, multi-center, IRB-approved study, Gallardo et al (2021) reported interim 6-month safety and effectiveness outcomes of 360° canaloplasty and 180° trabeculotomy using the OMNI Surgical System concomitantly with phacoemulsification in patients with OAG.  This trial included a total of 15 multi-subspecialty ophthalmology practices and surgery centers located in 14 states (Alabama, Arizona, Arkansas, Florida, Georgia, Iowa, Kansas, Montana, Nebraska, North Dakota, Oklahoma, Pennsylvania, Texas, and Wisconsin).  Subjects included patients treated with canaloplasty (360°) and trabeculotomy (180°).  Eligible patients had cataract and mild-to-moderate OAG with IOP of less than or equal to 33 mmHg on 1 to 4 hypotensive medications.  Medication wash-out before baseline diurnal IOP (Goldmann).  Effectiveness outcomes included mean IOP and medications.  Safety outcomes included AEs, BCVA and SSI.  Analysis included descriptive statistics and t-tests evaluating change from baseline.  A total of 137 patients were enrolled and treated.  Mean diurnal IOP after washout was 23.8 ± 3.1 mmHg at baseline.  At month 6, 78 % (104/134) were medication free with IOP of 14.2 mmHg, a mean reduction of 9.0 mmHg (38 %); 100 % (104/104) had a greater than or equal to 20 % reduction in IOP and 86 % (89/104) had IOP greater than or equal to 6 and less than or equal to 18 mmHg.  The mean number of medications at screening was 1.8 ± 0.9 and 0.6 ± 1.0 at month 6.  AE included transient hyphema (4.6 %) and IOP elevation greater than or equal to 10 mmHg (2 %).  There were no AE for loss of BCVA or recurring hyphema.  There were no SSI.  The authors concluded that canaloplasty followed with trabeculotomy and performed concomitantly with phacoemulsification had favorable intra- and peri-operative safety, significantly reduced IOP and anti-glaucoma medications through 6 months in eyes with mild-to-moderate OAG.  Moreover, these researchers stated that full 12-month results of the entire cohort will be reported upon study completion.

Furthermore, an UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2021) states that “All patients with glaucoma should receive treatment upon diagnosis.  Pharmacologic therapy, laser therapy (trabeculoplasty), and/or surgery (trabeculectomy) have been shown to lower intraocular pressure (IOP) in randomized trials.  However, there are little data on their efficacy in preventing deterioration of vision.  A limitation of available evidence is the dual challenge of accounting for ongoing advances in all three therapeutic strategies and assessing a key outcome, visual deterioration, that may take many years to develop”.  Moreover, this review does not mention canaloplasty and phacoemulsification as management / therapeutic options.

In a prospective, IRB-approved multi-center study, Gallardo et al (2022) reported the 12-month effectiveness outcomes of 360° canaloplasty and 180° trabeculotomy using the OMNI surgical system in combination with phacoemulsification in patients with mild-moderate open-angle glaucoma (OAG) and visually significant cataract.  This trial was carried out in 15 multi-subspecialty ophthalmology practices and surgery centers located in 14 U.S. states.  Subjects were patients treated with canaloplasty (360°) and trabeculotomy (180°); eligible patients had cataract and mild-moderate OAG with IOP of less than or equal to 33 mmHg on 1 to 4 hypotensive medications.  Unmedicated post-washout mean diurnal IOP (DIOP) was greater than or equal to 21 and less than or equal to 36 mmHg.  Medication washout was performed pre-operatively and before month-12 DIOP.  Effectiveness outcomes were IOP and IOP lowering medication use.  Safety outcomes included AEs and SSIs.  Evaluations were carried out at 1, 3, 6, and 12 months.  A total of 149 subjects underwent surgery and 120 were included in the final effectiveness analysis.  Mean (SD) unmedicated diurnal IOP was reduced from 23.8 (3.1) mmHg at baseline to 15.6 (4.0) at month 12 (-35 %) and medications (before washout) were reduced from 1.8 (0.9) at baseline to 0.4 (0.9) at month 12 (-80 %).  At month 12, 84.2 % of eyes achieved IOP reductions of greater than 20 % from baseline, 80 % of eyes were medication-free, and 76 % of eyes achieved IOP between 6 to 18 mmHg inclusive; AEs were uncommon.  Most were mild and self-limited including transient hyphema (9 of 149; 6 %) and transient IOP elevations (3 of 149; 2.0 %).  No eyes needed SSIs or experienced loss of VA that was attributable to the device or procedure.  The authors concluded that canaloplasty and trabeculotomy carried out with the OMNI surgical system at the time of phacoemulsification significantly lowered unmedicated mean DIOP and medication use 12 months post-operatively, with an excellent safety profile.  This procedure should be considered for eyes with mild-moderate OAG to reduce IOP, medication burden, or both

The authors stated that the lack of a control group was a drawback that precluded quantifying the contribution of elements from the phacoemulsification and OMNI procedures (as would be possible with a phacoemulsification-only arm) or comparison of OMNI to other MIGS procedures (as would be possible with an active comparator arm).  Phacoemulsification alone is known to lower IOP and the need for IOP-lowering medications in glaucomatous eyes.  These researchers have tried to mitigate this limitation by designing the statistical analysis plan around the relevant outcomes of phacoemulsification-only groups (which have been remarkably consistent albeit greater than what has been typically reported in other publications) in recent pivotal MIGS trials, specifically powering the study to detect an effect size in excess of that expected by phacoemulsification alone in eyes with mild-moderate OAG.  The decision to design this study without a cataract surgery only control group was not made lightly.  First, the availability of published data for large cohorts of similarly defined patient populations undergoing phacoemulsification only allowed reasonable estimation of the cataract surgery only treatment effect.  Second, in the early 2010ʹs when the pivotal studies for iStent, Hydrus, and CyPass were initiated, the treatment landscape for mild-to-moderate glaucoma in the U.S. was very different.  MIGS was a new modality with limited availability and options.  Standard treatment was generally medical (drops) or laser (SLT).  In contrast, by 2019 when the present study was designed there were several MIGS options available to patients and surgeons with increasing adoption.  In this evolving environment, execution of a trial where many patients would be randomized to a “no treatment” (aside from cataract surgery) control would have faced increased unwillingness of patients to participate and would arguably be less ethically sound given the many new therapeutic options available for mild-to-moderate glaucoma.

In a retrospective, observational study, Toneatto et al (2022) examined the effectiveness of ab-interno micro-catheterization and 360° viscodilation of Schlemm's canal (SC) performed with OMNI visco-surgical system in OAG together or not with phacoemulsification.  A total of 80 eyes from 73 patients with mild-to-moderate OAG underwent ab- interno SC viscodilation carried out with the OMNI system; 50 eyes (Group 1) underwent only SC viscodilation, while 30 eyes (Group 2) underwent glaucoma surgery + cataract extraction.  Primary success endpoint at 12 months was an IOP reduction higher than 25 % from baseline with an absolute value of 18 mmHg or lower, either on the same number or fewer ocular hypotensive medications, without further interventions.  Secondary effectiveness endpoints included mean IOP, number of medications and comparison of outcomes between groups.  Safety endpoints consisted of BCVA, AEs, and subsequent surgical procedures.  Primary success was achieved in 40.0 % and 67.9 % in Groups 1 and 2, respectively.  Mean IOP at 12-month follow-up showed a significant reduction in both groups (from 23.0 to 15.6 mmHg, p < 0.001, and from 21.5 to 14.1, p < 0.001, in Groups 1 and 2, respectively).  Mean medication number decreased in both groups (from 3.0 to 2.0, p < 0.001 and from 3.4 to 1.9, p < 0.001, in Groups 1 and 2, respectively); AEs included hyphema (2 eyes), mild hypotony (4 eyes), IOP spikes 1 month after surgery (1 eye); 12 eyes (15.0 %) required subsequent surgical procedures.  No BCVA reduction was observed.  The authors concluded that viscodilation of SC using the OMNI viscosurgical system, with or without cataract extraction, appeared to be a promising surgical procedure to effectively control and reduce IOP with a highly safer profile, even if a high percentage of eyes needed a medical treatment.  Moreover, these researchers stated that further studies are needed to report long-term results and complications, and to examine the real advantage of an associated trabeculotomy.

The authors stated that the drawbacks of this trial included the retrospective nature of collected data, the relatively low number of subjects included, the short follow-up period (12 months), and the enrollment of both eyes of the same patient in some cases.  Furthermore, not all eyes were naive to prior surgery: 13 had already underwent previous major glaucoma surgery (trabeculectomy and deep sclerectomy).  This choice was based on previous studies that have shown that canaloplasty can also be successfully carried out in patients with failed trabeculectomy in which the SC has been left mostly undamaged from previous filtering surgeries.  There was no standardized protocol for reducing or increasing medications; however, the medical therapy was adjusted to reach the target IOP on a case-by-case basis.  Follow-up was limited to 1 year.  Due to the limited number of patients included in this cohort, it was difficult to examine the role and influence of glaucoma types on surgery between the groups.  These investigators stated that future prospective studies are currently underway to aid in addressing this issue.  In particular, longer-term studies on a larger group of prospectively enrolled patients are needed to evaluate the duration of IOP reduction with this surgical technique.

In a prospective, case-series study, Grabska-Liberek et al (2022) examined clinical outcomes of combined viscodilation of Schlemm's canal and collector channels and 360° trabeculotomy as a standalone procedure or combined with cataract surgery in eyes with mild-to-moderate open-angle glaucoma (OAG).  The OMNI glaucoma surgical platform was employed to carry out the procedure either combined with phacoemulsification or as a standalone procedure.  Changes from baseline in IOP and IOP-lowering medications were evaluated through the first 12 months of a planned 24-month follow-up period.  Among 17 eyes of 15 subjects, mean IOP was reduced from 20.4 mmHg to 12.7-13.7 mmHg through 12 months of follow-up (p < 0.001 at every time-point) and mean medications reduced from 2.5 to 0.1-0.6 (p < 0.001 at every time-point).  IOP reductions in eyes undergoing stand-alone surgery were approximately 2 to 4 mmHg greater at each time-point compared to eyes undergoing surgery combined with phacoemulsification; this may be related to a higher baseline IOP in the former eyes (22.1 versus 18.5 mmHg); 6 eyes developed hyphema, of which 3 required wash-out for elevated IOP on the 1st post-operative day; 6 additional eyes had IOP elevations that resolved with medical management.  The authors concluded that viscodilation of Schlemm's canal and collector channels paired with ab interno trabeculotomy performed with a single integrated instrument (OMNI), whether as standalone or combined with phacoemulsification, effectively lowered both IOP and the need for IOP-lowering medications through 12 months of follow-up.  Moreover, these researchers stated that further study is needed to more robustly characterize outcomes and clarify the optimal use of this procedure.  This study is ongoing and 24-month data will be reported when available.

The authors stated that drawbacks of this study included its relatively small sample size (n = 15) as well as the absence of a comparator group.  This was a common drawback for studies of many of the minimally invasive glaucoma surgeries (MIGS) procedures, especially those cleared for marketing through the 510(k) equivalence-to-predicate pathway without the requirement for a pivotal trial, in which funding for well-designed and adequately-powered clinical trials is often not available.

Combined Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) with Ab Interno Canaloplasty (ABiC) in Conjunction with Phacoemulsification for the Treatment of POAG

In a prospective, interventional, non-comparative, case-series study, Al Habash and colleagues (2020) reported the surgical outcomes of combined gonioscopy-assisted transluminal trabeculotomy (GATT) with ab interno canaloplasty (ABiC) in conjunction with phacoemulsification for the treatment of patients with POAG.  This trial included POAG patients who underwent combined GATT and ABiC in conjunction with phacoemulsification performed between January 2018 and August 2018.  Main outcome measures include surgical success rate, changes in IOP, number of anti-glaucoma medications, corrected distance visual acuity (CDVA), and complications.  These researchers enrolled 19 patients (20 eyes) in this study.  The mean age was 61.2 ± 6 years, and all the patients completed a 12-month follow-up.  The overall success rate was 100 %.  The mean baseline IOP was 19.75 ± 4.68 mmHg, and at 12 months, the mean IOP was 13.30 ± 1.30 mmHg (IOP reduction of 32.7 %).  The baseline number of anti-glaucoma medications was 3.4 ± 0.6 (range of 2 to 4 medications), and after 12 months follow-up, the number was reduced to 1.1 ± 1.0 (range of 0 to 2 medications).  The CDVA for all 20 eyes was 0.85 ± 0.58 LogMAR at baseline, and 0.16 ± 0.30 LogMAR at 12-month follow-up.  Only 6 eyes developed hyphema, which had cleared by the 1st post-operative month, and 3 eyes needed medical treatment for post-operative IOP spikes.  The authors concluded that this study, to their knowledge, was the 1st to report on the outcomes of combined GATT with ABiC in conjunction with phacoemulsification for POAG.  According to the 12-month results of this trial, the combined procedure appeared to be safe and effective in decreasing the IOP and the number of anti-glaucoma medications in POAG patients.  These researchers stated that the drawbacks of this study included the limited number of patients (n = 19) and the lack of long follow-up duration.  Furthermore, it was a non-randomized study with no control group.  Despite these drawbacks, these investigators believed that combined GATT with ABiC in conjunction with phacoemulsification has the potential to be a great alternative option for the management of POAG, given the favorable efficacy outcomes and high safety profile in all eyes in this study.  These researchers recommended that more extensive RCTs be carried out with a longer follow-up in order to examine the long-term outcomes of this procedure in such patient population.

Furthermore, an UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2021) states that “All patients with glaucoma should receive treatment upon diagnosis.  Pharmacologic therapy, laser therapy (trabeculoplasty), and/or surgery (trabeculectomy) have been shown to lower intraocular pressure (IOP) in randomized trials.  However, there are little data on their efficacy in preventing deterioration of vision.  A limitation of available evidence is the dual challenge of accounting for ongoing advances in all three therapeutic strategies and assessing a key outcome, visual deterioration, that may take many years to develop”.  Moreover, this review does not mention canaloplasty and phacoemulsification as management / therapeutic options.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered if selection criteria are met:
66174	Transluminal dilation of aqueous outflow canal; without retention of device or stent [not covered with glaucoma gene therapy]
66175	with retention of device or stent [not covered with glaucoma gene therapy]
CPT codes not covered for indications listed in the CPB:
66170	Fistulization of sclera for glaucoma; trabeculectomy ab externo in absence of previous surgery [not covered if reported for viscocanalostomy or phacoviscocanalostomy]
ICD-10 codes covered if selection critreria are met:
H40.1110 - H40.1194	Primary open angle glaucoma
H40.1210 - H40.1294	Low-tension glaucoma
H40.1410 - H40.1494	Capsular glaucoma with pseudoexfoliation of lens
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
H40.001 -H40.10x+, H40.121+ - H40.1394, H40.151 - H42	Glaucoma
H44.511 - H44.519	Absolute glaucoma
Q15.0	Congenital glaucoma
T38.0X1A - T38.0X6S	Poisoning by, adverse effect of and underdosing of glucocorticoids and synthetic analogues [corticosteroid-induced glaucoma]
Combined phacoemulsification and viscocanalostomy with Ologen implant:
CPT codes not covered for indications listed in the CPB:
Viscocanalostomy with Ologen implant - no specific code:
66982	Extracapsular 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 cataract surgery (eg, iris expansion device, suture support for intraocular lens, or primary posterior capsulorrhexis) or performed on patients in the amblyogenic developmental stage [phacoemulsification and viscocanalostomy with Ologen implant]
66989	Extracapsular 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 cataract surgery (eg, iris expansion device, suture support for intraocular lens, or primary posterior capsulorrhexis) or performed on patients in the amblyogenic developmental stage; with insertion of intraocular (eg, trabecular meshwork, supraciliary, suprachoroidal) anterior segment aqueous drainage device, without extraocular reservoir, internal approach, one or more
66991	with insertion of intraocular (eg, trabecular meshwork, supraciliary, suprachoroidal) anterior segment aqueous drainage device, without extraocular reservoir, internal approach, one or more
ICD-10 codes not covered for indications listed in the CPB:
E08.36	Diabetes mellitus due to underlying condition with diabetic cataract
E09.36	Drug or chemical induced diabetes mellitus with diabetic cataract
E10.36	Type 1 diabetes mellitus with diabetic cataract
E11.36	Type 2 diabetes mellitus with diabetic cataract
E13.36	Other specified diabetes mellitus with diabetic cataract
H25.011 - H25.9	Age-related cataract
H26.001 - H26.9	Other cataract
H28	Cataract in diseases classified elsewhere
H40.1110 - H40.1194	Primary open angle glaucoma
Q12.0	Congenital cataract
Z98.4 - Z98.49	Cataract extraction status
Canaloplasty and trabeculotomy ab interno with the OMNI System combined with cataract surgery:
CPT codes not covered for indications listed in the CPB:
65820	Goniotomy
66174	Transluminal dilation of aqueous outflow canal; without retention of device or stent
HCPCS codes not covered for indications listed in the CPB:
OMNI System – no specific code
Other CPT codes related to the CPB:
66982	Extracapsular 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 cataract surgery (eg, iris expansion device, suture support for intraocular lens, or primary posterior capsulorrhexis) or performed on patients in the amblyogenic developmental stage; without endoscopic cyclophotocoagulation
66983	Intracapsular cataract extraction with insertion of intraocular lens prosthesis (1 stage procedure)
66984	Extracapsular cataract removal with insertion of intraocular lens prosthesis (1 stage procedure), manual or mechanical technique (eg, irrigation and aspiration or phacoemulsification); without endoscopic cyclophotocoagulation
66987	Extracapsular 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 cataract surgery (eg, iris expansion device, suture support for intraocular lens, or primary posterior capsulorrhexis) or performed on patients in the amblyogenic developmental stage; with endoscopic cyclophotocoagulation
66988	Extracapsular cataract removal with insertion of intraocular lens prosthesis (1 stage procedure), manual or mechanical technique (eg, irrigation and aspiration or phacoemulsification); with endoscopic cyclophotocoagulation
ICD-10 codes not covered for indications listed in the CPB:
H40.1110 - H40.1194	Primary open angle glaucoma
Combined gonioscopy-assisted transluminal trabeculotomy (GATT) with ab interno canaloplasty (ABiC) in conjunction with phacoemulsification:
CPT codes not covered for indications listed in the CPB:
65820	Goniotomy
66174	Transluminal dilation of aqueous outflow canal; without retention of device or stent [use and combination]
Other CPT codes related to the CPB:
66850	Removal of lens material; phacofragmentation technique (mechanical or ultrasonic) (eg, phacoemulsification), with aspiration
66982	Extracapsular 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
66983	Intracapsular cataract extraction with insertion of intraocular lens prosthesis (1 stage procedure)
66984	Extracapsular cataract removal with insertion of intraocular lens prosthesis (1 stage procedure), manual or mechanical technique (eg, irrigation and aspiration or phacoemulsification); without endoscopic cyclophotocoagulation
66987	Extracapsular 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
66988	Extracapsular cataract removal with insertion of intraocular lens prosthesis (1 stage procedure), manual or mechanical technique (eg, irrigation and aspiration or phacoemulsification); with endoscopic cyclophotocoagulation
ICD-10 codes not covered for indications listed in the CPB:
H40.1110 - H40.1194	Primary open angle glaucoma

The above policy is based on the following references: