Ab externo canaloplasty results and efficacy: a retrospective cohort study with a 12-month follow-up

Background The aim of this study is to review the outcomes of canaloplasty versus canaloplasty combined with phacoemulsification in a retrospective cohort study and to evaluate the efficacy of these methods in terms of intraocular pressure (IOP) lowering effect, postoperative complications and additional glaucoma surgery or reintroduction of medical therapy over a 12-month follow-up. Methods In a retrospective cohort study, 602 eyes with primary open angle glaucoma (POAG) were treated with canaloplasty or canaloplasty combined with phacoemulsification. The results were evaluated separately in two main groups; group A canaloplasty (262 eyes) and group B canaloplasty combined with phaco (322 eyes). Each group was then subdivided into three additional groups according to the severity of glaucoma. The criteria for successful treatment were evaluated between three IOP ranges; IOP ≤ 16 mmHg, 18 mmHg and 21 mmHg. Complete success was considered the percentage of eyes reaching target IOP with no medication and partial success with medication. Groups A and B subgroups were compared using the Kaplan Meier test. Mean IOP, reduction of antiglaucoma agents and additional IOP lowering methods were also evaluated. The follow-up time was 12 months. Statistical significance was set at p < 0.05. Results An incomplete intraoperative cannulation of Schlemm’s canal resulting in conversion to other glaucoma surgery occurred in 18 eyes (2.99%). In both of the main groups, postoperative hyphema, descemet membrane detachment and transient IOP rise were the most common postoperative complications. The mean IOP in group A and subgroups at 12 months was 13.26 ± 4.5 mmHg, 15.19 ± 3.97 mmHg and 18.09 ± 3.75 mmHg. Respectively in group B mean IOP was 14.51 ± 4.69 mmHg, 14.40 ± 4.11 mmHg and 14.25 ± 2.76 mmHg. Complete success was achieved in group A in 69.19, 74.51 and 74.31% of eyes. In group B complete success was achieved in 81.60, 77.33 and 83.33% of eyes respectively. Kaplan Meier between groups A and B was statistically significant for IOP ≤ 16 mmHg and IOP ≤ 21 mmHg (p = 0.0041 and p = 0.0312), but not for IOP ≤ 18 mmHg (p = 0.6935). Partial success for IOP ≤ 16 mmHg was 95.23 and 92.26%, for IOP ≤ 18 mmHg was 91.66 and 90.47% and for IOP ≤ 21 mmHg, 90.00 and 93.10%, in groups A and B respectively. Twenty-three eyes received additional surgery (3.93%), 10 trabeculectomies and 2 cyclophotocoagulation in group A, and 9 trabeculectomies and 2 cyclophotocoagulation in group B. Conclusion Canaloplasty and canaloplasty combined with phacoemulsification significantly lower the IOP and have a lower postoperative complication rate. Additional glaucoma surgery or medication following both procedures is necessary if target IOP is unsatisfactory. In this study, canaloplasty combined with phacoemulsification demonstrated superior success rate compared to canaloplasty alone.


Background
Glaucoma is regarded as one of the major causes leading to blindness in both the developed and developing countries. Recent studies estimate that about 66 million people worldwide are affected with glaucoma, concluding that half of these cases remain undiagnosed [1]. In all cases of people affected with this condition, early diagnosis and sufficient reduction of the intraocular pressure (IOP), either with drug therapy or with surgery, has been proven to reduce rapid progression of visual field defects [2][3][4]. Drug therapy is administered as the treatment of choice upon diagnosis and early detection of primary open angle glaucoma (POAG) is crucial. Surgery is required when IOP is not manageable with topical therapy or when the socio-economic situation favors it as a tradeoff over years of expensive drug therapies. Trabeculectomy though, is still regarded as the golden standard. It is a filtering operation with excellent results in IOP reduction and is highly cost effective. As a surgical procedure, it relieves IOP by removing part of the eye's trabecular meshwork and adjacent structures to allow drainage of aqueous humor from within the eye to underneath the conjunctiva where it is absorbed. However, its use has been highly correlated with severe, adverse sight threatening complications and difficult post-operative management [5,6]. Non penetrating techniques were developed as controlled glaucoma incisional surgery without a full thickness opening. Canaloplasty in particular has been in the spotlight in the recent years as a viable option and considered the evolution of viscocanalostomy [7,8]. It is a procedure designed to enhance and restore the eye's natural drainage system and provide sustained reduction of intraocular pressure. After gaining access to Schlemm's canal, a microcatheter is inserted inside and navigated 360°around it, dilating the main drainage channel and its smaller collector channels through the injection of viscoelastic. The catheter is then removed and a suture is placed within the canal and tightened. Aqueous outflow is restored by tensioning Schlemm's canal with a 10.0 polypropylene suture. In this retrospective cohort study, 602 eyes with POAG were treated with canaloplasty or canaloplasty combined with phacoemulsification. This retrospective study evaluates the results between two groups in three IOP ranges, drug therapy reduction, intraoperative complications and additional IOP lowering methods including surgery in a 12-month follow-up.

Methods
Between 2010 and 2013, a total of 439 patients already diagnosed with POAG were referred to our clinic for surgery due to uncontrolled IOP despite maximal local and systemic medication, progression of visual field defects or drug therapy intolerance. A total of 602 eyes were initially evaluated and were scheduled to undergo canaloplasty (Group A) or canaloplasty combined with phaco (Group B) due to lens opacity. All patients underwent a baseline standard ophthalmic examination including ophthalmic history with previous ocular surgeries or laser treatments, glaucoma medication use, Humphrey visual field 30-2 SITA Fast test, IOP measurement using Goldmann applanation tonometry, visual acuity testing in decimal Snellen, slit-lamp biomicroscopy for anterior segment evaluation, gonioscopy with angle grading and indirect ophthalmoscopy for fundus assessment. The two main groups were then divided according to the Hodapp, Parrish, Anderson (H-P-A) classification system [9], into three subgroups. Demographics are presented in Table 1. All patients were operated on St. Johannes Hospital Eye Clinic, Dortmund, Germany by MK and written consent was obtained prior to surgery. The tenets of the Declaration of Helsinki were fully respected. The operation was performed ab externo by placing the first flap at 11 o'clock regardless of left or right eye. After preparation of the second scleral flap, access to Schlemm's canal was gained and a microcatheter iTRACK™ 250 (Ellex Medical Lasers Ltd., 3-4 Second Avenue, Mawson Lakes, SA 5095 Australia) was inserted. Dilation was performed through the injection of sodium hyaluronate, Healon GV®, 0.85 ml from Abbott (Abbott laboratories, Lake Bluff, Illinois, United States). The microcatheter was then removed and tensioning of the canal with a 10.0 polypropylene suture was performed. Eighteen eyes from both groups were converted to other glaucoma surgery intraoperative due to incomplete cannulation and were excluded from the analysis (Table 1.) Patients remained in our clinic and were discharged at 1.51 ± 0.5 days for Group A and 1.48 ± 0.5 days for Group B. The post-operative regimen was antibiotics combined with corticosteroids eye drop solution 5 times daily and eye ointment 1 time daily, replaced after 2 weeks with non-corticosteroid anti-inflammatory agents 5 times daily for 2 weeks. Follow up took place at 1 day, 2 weeks, 1 month, 3 months, 6 months and 12 months. Postoperative follow up checks included IOP measurement using Goldmann applanation tonometry, visual acuity testing in decimal Snellen, slit-lamp biomicroscopy for anterior segment evaluation and assessment of complications with decision of subsequent surgical interventions. Humphrey visual field 30-2 SITA Fast test was repeated again in 12 months. When additional surgery was required, full thickness opening surgery or transscleral diode cyclophotocoagulation were performed due to inadequate IOP lowering effect, failure to comply with medical therapy or both. We did not perform YAG -Goniopuncture in any of the 584 eyes. Trabeculectomy scleral flap was created at 2 o'clock and was combined with mitomycin 0.02% and ologen® Ologen is a biodegradable and implantable porcine extracellular matrix made of atelocollagen cross-linked with glycosaminoglycan, specifically configured to support and modulate tissue repair processes in connective and epithelial ocular tissues. Transcleral diode cyclophotocoagulation was performed in danger of wipe out syndrome or when conjunctiva was limiting the success of full thickness opening surgery. Complete success was regarded as obtaining postoperative IOP ≤ 21 mmHg, ≤ 18 mmHg, and ≤ 16 mmHg without medical therapy and partial success an IOP ≤ 21 mmHg, ≤ 18 mmHg, and ≤ 16 mmHg with medical therapy. Success is reported in the percentage of eyes reaching these goals using the Kaplan Meier test. IOP percentage reduction and medical therapy percentage reduction to baseline was also evaluated. MedCalc was used for statistical purposes and significance was given at p < 0.05. Regarding distribution, Kolmogorov-Smirnov and chi-squared test were performed. Follow up duration was 12 months. The local institutional review board committee approved this retrospective study.

Results
A total of 18 eyes (2.99%) were converted intraoperatively to other procedures and were excluded from the analysis. In total, 584 eyes were analyzed (Table 1). Hyphema, descemet membrane detachment, transient IOP raise or hypotony were among the post-operative complications ( Table 2). Mean IOP baseline for group A with target IOP ≤ 16 mmHg was 19.15 ± 6.42 mmHg with 2.71 ± 0.95 antiglaucoma agents and reduced at 12 months to 13.26 ± 4.50 mmHg with 0.28 ± 0.99 agents (Figs. 1 a and 2 a). Medication reduction reached 91.43 ± 30.74% (Table 3) and IOP reduction reached 27.88 ± 29.50% at 12 months. By the end of the follow up, complete success was achieved in 69.19% and partial success in 95.23% of cases. Additional surgery was performed in 9 eyes (    (Table 2). Mean IOP and medication reduction over the 12-month follow-up for both groups with target IOP subgroups was adequate (Figs. 1 a-f and 2 a-f, Table 3). Mean distance corrected visual acuity (DCVA) in group A was stable except from the first day to the first month in most subgroups. Some fluctuations in DCVA between the follow up were due to ocular surface problems (Fig. 3 a,c,e).
In group B and subgroups DCVA compared to baseline increased significantly (Fig. 3 b,d,f). Kaplan Meier Log rank test was statistically significant between Group A and B for target IOP ≤ 16 mmHg and target IOP ≤ 21 mmHg (p = 0.0041 and p = 0.0312 respectively) ( Fig. 4)

Discussion
With the advent of canaloplasty in the last decade as a new surgical option in managing IOP in glaucoma  patients, an increasing number of surgeons have started to favor this approach for its safety, efficacy and overall good results. Canaloplasty lowers IOP by a 360-degree viscodilation and tensioning of the Schlemm canal. This procedure is still less likely to be successful in eyes with a nonreversible collapse of collector channels or other outflow pathways that cannot be mechanically enlarged [10]. Episcleral venous pressure and transtrabecular diffusion plays a significant role in the outcomes of canaloplasty procedure. Chanelography and provocative gonioscopy can be used as a tool to predict the outcomes preoperatively [11]. Overall, the efficacy and safety of canaloplasty is well documented [12][13][14][15][16][17][18][19] [14]. We demonstrate similar results in groups A and B in terms of mean IOP reduction and mean medication reduction (Table 3). We also reported transient IOP elevation in 19 eyes group A (7.25%) and group B in 33 eyes (10.24%). These eyes where either treated with medication or with additional surgery if IOP was not manageable (Table 2). Cataract formation following canaloplasty was not reported in group A. Brusini et al. [15,16]    follow up. Our partial success rate was above 90% in both groups and overall we demonstrated an adequate reduction of mean IOP and reduced post-operative need for medication. Our percentage reduction of IOP was high at 1 day post-op and gradually reduced with one group showing 8% reduction while other groups showing 16 to 17% and some groups even above 25%. This could be explained from the low baseline IOP in all our groups that were receiving at baseline up to 5 antiglaucoma agents to maintain IOP, in particular for group A (IOP ≤ 21 mmHg) whose baseline mean IOP with medication was 21.25 ± 5.67 mmHg. The results of this group in comparison to all other groups in all parameters were inferior. We believe that this interesting result was due to failure of collector channels enlargement possibly resulting from increased episcleral venous pressure and decreased transtrabecular diffusion. Nonetheless, the mean IOP of this group was below its target and the medication reduced from 2.69 ± 1.2 to 0.72 ± 1.0 at 12 months, a reduction of 65.15 ± 50.80% from baseline. Between groups A and B, the results were superior in most parameters for group B, showing that canaloplasty with phaco provides better outcomes as shown in other studies [14,[17][18][19]. Overall, we reported acceptable complete and partial success rates and managed to surgically reduce IOP with minor complications and a few additional surgical interventions.

Conclusions
Overall, canaloplasty alone and canaloplasty combined with phacoemulsification are safe surgical procedures that significantly reduce IOP in POAG. An incomplete intraoperative cannulation of Schlemm's canal can result in conversion to other glaucoma surgery. The most common post-operative complications are hyphema, DMD, hypotony and transient IOP elevation that requires additional medication and possibly surgical intervention if medication fails. Canaloplasty combined with phacoemulsification provided superior results in terms of achieving the target IOP with no additional medication in comparison to canaloplasty alone.