Long-term effect of canaloplasty on intraocular pressure and use of intraocular pressure–lowering medications in patients with open-angle glaucoma

An ongoing retrospective study found that canaloplasty performed alone or with cataract extraction in patients with OAG resulted in consistently reduced IOP and use of IOP-lowering medications up to 42 months postoperatively. Purpose: To assess the long-term safety and effectiveness of canaloplasty in reducing intraocular pressure (IOP) and use of IOP-lowering medications in eyes with open-angle glaucoma (OAG). Setting: Surgical center (Augencentrum Köln, Köln, Germany). Design: Retrospective study. Methods: 206 eyes from 130 patients were included. Canaloplasty was performed using the VISCO360 or OMNI surgical system as a stand-alone procedure in 22 eyes and concomitantly with cataract extraction (CE) in 185 eyes with chronic OAG insufficiently controlled or intolerant to IOP-lowering medications. The number of hypotensive medications and IOP were recorded at baseline, day 1, week 1, month 1, month 3, and every 3 months thereafter, with the last follow-up visit at 36 ± 6 months postoperatively. Patients were stratified by baseline IOP (Group 1, IOP >18 mm Hg; Group 2, IOP ≤18 mm Hg). Treatment success in Group 1 was defined as a reduction in IOP and the use of IOP-lowering medications; Group 2 success was defined as maintenance of a lower IOP and a reduction in medication use. Results: The preoperative mean IOP of both groups was 21.1 ± 8.8 mm Hg, with a mean of 2.0 ± 0.9 hypotensive medications. The primary success end point was met by 73% of patients, with a mean IOP reduction in Group 1 (131 eyes; 21.8 to 15.6 mm Hg, P < .0001) and a maintenance of IOP control in Group 2 (76 eyes; 15.4 to 13.9 mm Hg, P = .24). Medications decreased from 2.2 ± 0.9 to 0.9 ± 1.1 in Group 1 (P = .024) and from 1.8 ± 0.8 to 0.7 ± 1.0 in Group 2 (P = .003). Conclusions: Canaloplasty alone or in conjunction with CE with the VISCO360 or OMNI surgical system is a safe, tissue-sparing, and effective minimally invasive glaucoma surgery, using a clear corneal incision in phakic or pseudophakic eyes. Canaloplasty performed with both evaluated devices achieved statistically significant, consistent, and clinically meaningful reductions in IOP and use of IOP-lowering medications in adult patients with OAG. In the consistent cohort (n = 42), the IOP-lowering effect lasted up to 42 months, with ongoing data collection expected to describe long-term effectiveness of this intervention.

G laucoma is the leading cause of irreversible blindness. 1 A meta-analysis of population-based studies estimated that 2.22 million individuals in the United States were affected by open-angle glaucoma (OAG) in 2000, with a projected increase to 3.36 million by 2020 because of a rapidly aging population. 2 Overall, the worldwide prevalence of glaucoma is estimated in individuals aged 40 years and older to be 3.5%. 3 Treatments for glaucoma are undertaken with the goal of lowering intraocular pressure (IOP), by using either IOPlowering medications or a glaucoma surgery. However, a medical approach to glaucoma treatment is often limited by patient compliance, and traditional glaucoma filtration surgery may be short-lived in its benefits because of postoperative complications. 4 Minimally invasive glaucoma surgery (MIGS) procedures have been developed to address the limitations of medical management or traditional glaucoma filtration surgery and have increased in popularity in recent years. 5 In general, trabecular meshwork and Schlemm canal (SC)-based procedures are considered the safest of the available MIGS procedures. 6 Canaloplasty is a nonfiltering MIGS to restore the natural aqueous outflow that addresses all points of resistance in the outflow pathway, including trabecular meshwork, SC, and scleral collector channels. Traditional canaloplasty procedures involved an invasive ab externo approach that required full-thickness scleral incisions, whereas recent advances in canaloplasty using OMNI or VISCO360 devices (Sight Sciences) allow for an ab interno approach that preserves the sclera and conjunctiva. 4,7 In our previous analysis, 106 eyes from 71 consecutive patients who underwent canaloplasty with the VISCO360 or OMNI surgical systems, with or without cataract surgery, were evaluated at 12 ± 3 months. In Group 1 (baseline IOP >18 mm Hg), all eyes available at the time of analysis (n = 72) had a 41.0% reduction in mean IOP (from 24.6 ± 7.1 mm Hg to 14.6 ± 2.8 mm Hg), 87% (n = 62) of which showed an IOP reduction of ≥20% with no increase in IOP-lowering medications. In Group 2 (baseline IOP ≤18 mm Hg), all eyes (n = 34) maintained their baseline IOP at all postoperative visits. In both groups, a significant decrease (>89%) in the mean number of IOP-lowering medications was seen at 12 months with 86% of eyes medication free, with no increase in IOP. 4 The VISCO360 surgical system is a single-handed surgical device that restores normal aqueous outflow through the automatic delivery of a predetermined amount of viscoelastic fluid, allowing for the viscodilation of up to 360 degrees of the SC and collector channels through a single clear corneal incision. 8 The VISCO360 device was CE marked in 2015 and was commercially launched in 2018. The OMNI surgical system is an upgraded version of VISCO360, which is a new, implantfree MIGS device that can be used to perform canaloplasty and trabeculotomy in conjunction with cataract surgery or as a stand-alone procedure in phakic/pseudophakic eyes to lower IOP in adult patients with primary OAG (POAG). 8 An illustration of these devices and the corresponding surgical technique is available in Figure 1.
In June 2021, we conducted a retrospective review of canaloplasty using the VISCO360 or using the OMNI surgical system as part of an ongoing analysis of a realworld population of patients undergoing treatment for OAG.

Study Design
This single-center, consecutive, open-label, noninterventional retrospective surgical case series evaluated the safety and effectiveness of canaloplasty using either the VISCO360 or OMNI surgical systems in OAG. The study was conducted at Eye Center Cologne in Cologne, Germany, between December 2015 and May 2018. Full trial details and initial 12-month findings of this trial were published in 2019. 4 This analysis focuses on findings from 36 ± 6 months of extended follow-up.
The corrected distance visual acuity (CDVA) was assessed at each visit using Snellen charts. Preoperative and all postoperative follow-up visits included IOP assessment with applanation tonometry (without medication washout), IOPlowering medication documentation, slitlamp examination, and gonioscopic assessment (all 4 quadrants). Follow-up visits occurred at day 1, week 1, month 1, month 3, and every 3 months thereafter, with the last follow-up visit occurring at 36 ± 6 months postopertively. Fundus evaluation, including cupto-disc ratio (dilated examination at baseline, month 6, and every 6 months thereafter), was performed, as well as visual field testing every 12 months using the 24-2 SITA Standard test (Humphrey Field Analyzer II, Carl Zeiss Meditec AG). Adverse events (AEs) and secondary surgical interventions were also reported at each follow-up visit.
Patients received IOP-lowering medications until the day of surgery. Patients receiving anticoagulation therapy were not required to discontinue these medications.
This study was performed in accordance with the tenets of the Declaration of Helsinki. This study was considered noninterventional, as no prospective treatment assignments were made, all assessments were consistent with routine standard of care, and patient data were therefore collected as a retrospective review of findings from routine medical practice. In consideration of this noninterventional study design, the Landesärztekammer Dusseldorf Ethics Committee reviewed the study protocol and determined that approval was not required and waived informed consent. Patient data were anonymized before analysis.

Patients
As previously described, this retrospective analysis reflected a realworld population of patients receiving canaloplasty to treat OAG. Adult patients (18 years of age or older) with OAG who underwent canaloplasty either as a stand-alone procedure (pseudophakic or phakic) or in conjunction with cataract extraction (CE) using either VISCO360 or OMNI surgical systems were included in this study. Like previous analysis, patients were divided into 1 of 2 groups based on their baseline (presurgery) IOP. Patients in Group 1 had a baseline IOP of >18 mm Hg and therefore considered insufficiently controlled with their current Figure 1. A: OMNI surgical system. B: VISCO360 viscosurgical system. Illustration of the device showing a handpiece with a microcatheter, control wheel for advancing and retracting the microcatheter, viscoelastic reservoir/infusion pump, and a locking mechanism. Images are sourced from Sight Sciences, http:// sightsciences.com, and used with permission. C: Schematic of the circumferential viscodilation of the SC through clear corneal incision. The VISCO360 or OMNI cannula tip creates an opening into the SC. A controlled volume of viscoelastic fluid is delivered as the microcatheter is retracted back. OVD = ophthalmic viscosurgical device; SC = Schlemm canal medical regimen; those in Group 2 had a baseline IOP of ≤18 mm Hg and were therefore considered adequately controlled with their current medical regimen but intolerant to the medical treatment. The choice of an IOP threshold of 18 mm Hg is based on a definition made in the Advanced Glaucoma Intervention Study as a level that, if maintained over time, was associated with a lower risk of long-term disease progression. 9 Patients with terminal glaucoma were treated with canaloplasty according to the described procedures and were included in this study because they were using anticoagulation drugs that could not be discontinued or presented with comorbidities that put them at excessive risk with procedures that required general anesthesia or scleral preparation. Key exclusion criteria were diagnosis of glaucoma other than OAG, prior glaucoma surgery other than selective laser trabeculoplasty, and retinal vascular occlusion.
In defining treatment success, eyes with a high baseline IOP (Group 1) were expected to show a reduction in IOP and in the use of IOP-lowering medications; eyes with a lower baseline IOP (Group 2) were expected to maintain a low IOP and show a reduction in the use of IOP-lowering medications.

Study Procedure
The ab interno canaloplasty procedure using either the VISCO360 or OMNI surgical system has been previously described in multiple studies. 4,10-13 Although the OMNI surgical system is used for trabeculotomy and canaloplasty, we only performed canaloplasty in these patients. A Swan Jacob goniolens was used in all cases. All eyes enrolled in the study received 360-degree microcatheterization and viscodilation of the SC using the VISCO360 or OMNI surgical system. For eyes in which ab interno canaloplasty was performed in conjunction with CE (185 eyes), the device was introduced into the anterior chamber by the way of a single, self-sealing, 2.4 mm clear corneal incision, and the ab interno canal viscodilation procedure was performed after CE was successfully completed. For eyes receiving ab interno canaloplasty as a stand-alone procedure (22 eyes; 6 phakic and 16 pseudophakic), the cannula was introduced into the anterior chamber through a single, self-sealing, 1.8 mm clear corneal incision. The VISCO360 and OMNI surgical systems are designed to advance the microcatheter in 2 segments of 180 degrees to navigate the entire 360-degree circumference of the SC. A temporal approach was used in both stand-alone and combined procedures. The cannula was positioned at the desired location, and then an opening into the SC was created with the cannula tip. The finger wheel of the device was used to gently advance the microcatheter out of the cannula tip and into the SC, and the microcatheter was then advanced 180 degrees around the SC. The microcatheter was then retracted back into the cannula tip, at which time a controlled volume of Healon GV was delivered, resulting in the dilation of the SC along its entire length. This process was repeated along the other 180 degrees of the SC to achieve a full 360degree circumferential canal viscodilation, which was followed by irrigation and aspiration of the anterior chamber.

Postsurgical Management
Postoperatively, patients received a fixed combination topical gentamicin/dexamethasone (DEXAGENT) 5 times daily for the first week, followed by dexamethasone drops (DEXAPOS) 4 time daily for the second week, followed by a tapering of dose. Patients were evaluated at day 1 postoperatively for a safety check, with follow-up visits occurring at week 1, month 1, month 3, and every 3 months thereafter for the evaluation of CDVA, IOP, medication use, fundus, the anterior chamber, and the angle.

Outcome Measures
Effectiveness was assessed at 36 ± 6 months and compared with baseline measures. For patients in Group 1, the primary effectiveness outcome was change in the mean IOP and the mean number of IOP-lowering medications from baseline to 36 months; the secondary outcome measure was the proportion of eyes with IOP reduction ≥20% relative to baseline at 36 months, without any increase in the number of IOP-lowering medications. For patients in Group 2, the primary effectiveness outcome was the change in the mean number of IOP-lowering medications from baseline to 36 months. The proportion of eyes achieving medication freedom without an increase in IOP was also assessed for both patient groups. Visual field measurements were conducted every 12 months, before and as follow-ups after the procedure.
The primary safety outcome in this analysis was the frequency of any ocular AEs and any secondary surgical interventions.

Statistical Analysis
Descriptive statistics were used to summarize all data. Calculations of 95% CIs of the percentage per binomial distribution were performed for change over time in categorical values. The 95% CIs of the mean per t distribution were calculated for change over time in numeric values. A paired t test with post hoc Tukey adjustment to account for multiplicity was performed to compare baseline with follow-up IOP values and the number of IOP-lowering medications. P values less than 0.05 were considered statistically significant. Effectiveness outcomes were subgrouped by baseline IOP, with results presented separately for both study groups. Statistical analyses were performed with SAS v. 9.3 (SAS Institute, Inc.).

RESULTS
All patients included in this analysis were diagnosed with OAG, with a mean age of 75.0 ± 7.7 years (range, 54 to 91 years). The number of eyes included in this study reflects realtime analysis from an ongoing data collection effort on 206 eyes of 130 patients. Preoperative mean IOP was 21.1 ± 8.8 mm Hg, with a mean of 2.0 ± 0.9 hypotensive medications. Postoperative mean medicated IOP ranged from 13.7 ± 7.3 to 16.1 ± 5.1 mm Hg, with a mean postoperative IOP of 15.3 ± 3.0 mm Hg. The mean medication burden at the last follow-up was reduced to a mean of 0.9 and 0.7 in Groups 1 and 2, respectively (59% to 61% medication reduction from preoperative burden) (Figure 2). The primary success end point was met by 73% of patients, with a mean IOP reduction in Group 1 (131 eyes; 21.8 to 15.6 mm Hg, P < .0001) and a maintenance of IOP control in Group 2 (76 eyes; 15.4 to 13.9 mm Hg, P = .24). Medications decreased from 2.2 ± 0.9 to 0.9 ± 1.1 in Group 1 (P = .024) and from 1.8 ± 0.8 to 0.7 ± 1.0 in Group 2 (P = .003). Visual acuity increased from a mean of 0.58 ± 2.2 to 0.87 ± 2.3.
In the 22 eyes that received stand-alone canaloplasty, the mean IOP was reduced from 25.9 to 15.5 mm Hg (40% reduction), whereas medication use was maintained (2.9 vs 3.0 at 36 ± 6 months). On postoperative day 1, there were 14 IOP spikes of 25 to 50 mm Hg. These spikes resolved within days and were not observed at postoperative week 1.
A total of 58% of patients were medication free at 36 ± 6 months. No AEs were reported during the follow-up period beyond those reported in the original analysis, most of which were AEs that are commonly observed in MIGS, and comparable or lower than those reported in other MIGS studies. 4,14 Visual field mean defect values were stable, with mean preoperative and postoperative values of À6.36 and À6.20, respectively. The overall visual acuity significantly improved from a baseline mean of 0.60 ± 0.19 to 0.89 ± 0.22 (P < .0001).

Findings by Glaucoma Type
Changes from baseline to 36 ± 6 months were also analyzed by glaucoma type, as presented in Figure 3. Eyes with POAG, pseudoexfoliation glaucoma, pigmentary glaucoma, and terminal glaucoma all exhibited sustainable reductions in IOP from baseline to the time of analysis. Medication use decreased from baseline in all glaucoma types, including those with terminal glaucoma (Table 1).
Complications were most frequently reported in eyes with POAG (Table 2). Reported complications included 22 cases of hyphema: 17 cases of <1 mm, 4 cases of 1 to 3 mm, and 1 case of >3 mm. The >3 mm hyphema case required a secondary anterior chamber revision. Three secondary glaucoma surgeries were required (1.4%), all of which were ab externo canaloplasties (31-month postoperative, initial stand-alone pseudophakic eye; 19-month postoperative, initial combined surgery; 5-month postoperative, initial stand-alone phakic eye). Other follow-up surgeries included 3 series of intravitreal injections for myopia and choroidal neovascularization and 3 pars plana vitrectomies for membrane peeling.

DISCUSSION
MIGS procedures with an ab interno approach have become increasingly common in recent years because it is recognized as a safe and effective strategy for achieving long-term IOP control. This option allows for earlier surgery to address mild to moderate glaucoma that achieves a target IOP with fewer medications. 15,16 As noted in other studies, the OMNI and VISCO360 viscosurgical systems help support surgeons because they perform procedures such as ab interno or ab externo canaloplasty, recognizing that both require a substantial amount of training. These devices are designed to achieve easier cannulation of the SC and more consistent viscodilation of outflow pathways. 15 Canaloplasty with VISCO360 or OMNI systems achieved statistically significant, persistent, and clinically meaningful reductions in IOP and the use of medications in adult patients with OAG, confirming previous findings from a 12month analysis. 4 In this small set of eyes treated with the VISCO360 or OMNI, the IOP-lowering effect lasted up to 42 months. Consistent with the initial 12-month analysis, IOP and medication reduction was maintained across all postoperative visits at 36 months. Visual field measurements were found to be stable at the last follow-up available, and visual acuity improved significantly as a result of cataract surgery at this reported follow-up of at least 36 months.
These real-world clinical outcomes of ab interno, tissuesparing, less invasive canaloplasty continue to reflect equivalent to those reported with a more invasive, ab externo canaloplasty procedure. In an international, multicenter prospective study, an ab externo canaloplasty procedure was found to be safe and effective at reducing IOP and medication use up to 3 years after the procedure. 17 A retrospective, singlecenter, paired-eye study directly compared ab interno and ab externo canaloplasty with tensioning suture, reporting comparable effects of ab interno canaloplasty on IOP and medication reduction at 12 months in patients with POAG. 18 Multiple analyses of ab interno canaloplasty with or without cataract surgery using the VISCO360 or OMNI have been reported. One retrospective, single-center, consecutive case series of ab interno canaloplasty, with or without cataract surgery, evaluated changes in mean IOP and the mean number of medications in 89 eyes of 64 patients with OAG. Eyes with previous incisional glaucoma surgery and those with less than 90 degrees of viscodilation were excluded from the study. At 18-month follow-up, mean IOP decreased from a baseline of 24.5 ± 8.3 mm Hg to a postoperative IOP of 15.8 ± 2.5 mm Hg (P < .001), representing a 36% reduction from baseline. Medications were reduced from 2.5 ± 1.3 to 1.7 ± 1.5 (P < .05), representing a 32% reduction. Reductions in mean IOP and medication use were similar between those receiving the ab interno canaloplasty alone or in conjunction with cataract surgery. 19  The ROMEO study was another retrospective study that evaluated the safety and effectiveness of sequential canaloplasty and trabeculotomy with the OMNI surgical system combined with cataract surgery in patients with OAG. Eyes were stratified by baseline IOP, with Group 1 >18 mm Hg and Group 2 ≤18 mm Hg. Treatment success at the 12month analysis was defined as: (1) having ≥20% reduction in IOP or IOP between 6 and 18 mm Hg (inclusive) and (2) on the same number or fewer medications from baseline without secondary surgical intervention. The primary success end point was met by 79% and 81% in Groups 1 and 2, respectively. Mean IOP was reduced in Group 1 (21.9 to 15.1 mm Hg, P < .0001) and remained controlled in Group 2 (14.1 to 13.4 mm Hg, P = .3177). Medications were reduced 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 consistent with cataract or angle surgery and included mild inflammation (11%), IOP spikes (5%), and hyphema (4%). A total of 4 patients (5%) required a secondary surgical procedure. 11 Another analysis from the ROMEO study reported outcomes with sequential canaloplasty and trabeculotomy with the OMNI system in pseudophakic patients with mild-to-moderate OAG. This analysis included 48 patients and similarly stratified groups by baseline IOP. The primary success end point was met by 73% of patients, with a mean IOP reduction in Group 1 (21.8 to 15.6 mm Hg, P < .0001) and a maintenance of IOP control in Group 2 (15.4 to 13.9 mm Hg, P = .24). Medications decreased from 1.7 ± 1.3 to 1.2 ± 1.3 in Group 1 (P = .024) and from 2.0 ± 1.3 to 1.3 ± 1.3 in Group 2 (P = .003). As in the other ROMEO cohort, AEs were typical for the patient population undergoing angle surgery and included mild inflammation (13%), IOP spikes (6%), hyphema, corneal edema, and CDVA loss (all 4%). A total of 5 patients (10%) required a secondary surgical procedure. 12 More recently, a prospective multicenter study of 360-degree canaloplasty and 180-degree trabeculotomy using the OMNI surgical system with concomitant phacoemulsification in patients with mild-to-moderate OAG was conducted. The study included 15 ophthalmology practices in 14 U.S. states and included changes in mean IOP and medications as effectiveness outcomes. In an initial 6-month interim analysis of outcomes from 137 patients, mean IOP was reduced by 38%, declining from 23.8 to 14.2 mm Hg. A total of 78% of patients were medication free at 6 months, and 100% had a ≥20% reduction in IOP. In addition, 86% of patients had an IOP of between 6 and 18 mm Hg at 6 months. AEs included transient hyphema (4.6%) and IOP spike ≥10 mm Hg (2%). 8 Consistent with these are other studies of MIGS that observed AEs in the initial 12-month follow-up were infrequent and were comparable with or lower than AEs found in a meta-analysis of MIGS studies. [11][12][13][14]19,20 In this analysis of patient follow-up of at least 36 months, there were no reports of AEs or decrease in CDVA in patients undergoing canaloplasty, which is consistent with other MIGS studies.
Our findings are based on a single-center retrospective case series. As both eyes from 1 patient may have been included in our analysis when both met the eligibility criteria, our statistical analysis may be limited in the ability to consistently maintain independent data points. The majority of eyes (89.8%) included in this analysis received canaloplasty in conjunction with cataract surgery. As cataract is the most common comorbidity in patients with glaucoma, simultaneous cataract and glaucoma surgery are routine in practice. In such cases, IOP reduction can be attributed to both the procedures. 21 It is noteworthy that, in small subgroup (n = 22) included in this study eyes that underwent a stand-alone canaloplasty, the percentage reduction in IOP was 40% (from 25.9 to 15.5 mm Hg with a maintained medication burden), which was greater than that seen in the overall cases included in the analysis, the majority of which received OMNI in conjunction with cataract surgery (28% reduction in IOP with a 62% reduction in medication burden). The readers should also take into consideration the number of medications used in each group at 36 months. Cataract surgery in patients with glaucoma has been previously observed to achieve an IOP reduction ranging between 0.6 mm Hg and 2.5 mm Hg at 1 year. 22 Patient inclusion criteria were purposefully broad to reflect real-world practice. The study also lacked a control group to compare outcomes more reliably over time with other interventions. Nevertheless, the durable efficacy and favorable safety profile demonstrated after 36 months of follow-up suggest that ab interno canal viscodilation with the VISCO360 or OMNI surgical systems is an attractive and minimally invasive strategy for the treatment of patients with OAG.
Canaloplasty performed using the VISCO360 or OMNI surgical system is a safe, tissue-preserving, and effective MIGS option that allows surgeons to perform multiple procedures (canaloplasty and CE) using a clear corneal incision or perform a stand-alone procedure in phakic or pseudophakic eyes. Both devices successfully and consistently performed canaloplasty and achieved statistically significant and clinically meaningful reductions in IOP and the use of medications in adult patients with OAG. Ongoing data collection is expected to better describe the persistence of these real-world outcomes, and further studies are warranted to confirm the persistence of benefit of this intervention in patients with OAG.

WHAT WAS KNOWN
Minimally invasive glaucoma surgery (MIGS) procedures are increasingly used as a safe and effective alternative to medical management or traditional glaucoma filtration surgery in patients with glaucoma. Canaloplasty is a nonfiltering MIGS to restore the natural aqueous outflow system in the eyes of patients with glaucoma without requiring an implant to be left behind in the eye. Although traditional canaloplasty procedures involved an invasive ab externo approach that required full-thickness scleral incisions, recent device innovations allow for addressing all points of resistance in the outflow pathway through a clear corneal ab interno approach that preserves the sclera and conjunctiva.

WHAT THIS PAPER ADDS
Confirming findings from similar studies and an initial analysis of 12-month outcomes in the same clinic and patient cohort, an MIGS ab interno canaloplasty procedure with or without cataract extraction was safe, tissue-sparing, and effective, allowing surgeons to perform both procedures using a single clear corneal incision with or without cataract extraction. To the authors' knowledge, this is the first publication that shows consistent reductions in IOP and use of medications in adult patients with open-angle glaucoma up to 42 months postoperatively.