The ABCs of canaloplasty

Canaloplasty is a minimally invasive glaucoma surgery that essentially involves 360° catheterization as well as viscodilation of the Schlemm canal. Not only is canaloplasty designed to treat the entire conventional outflow pathway, facilitating flow through the trabecular meshwork, Schlemm canal, and collector channels, but it does so without a stent and without removing tissue.

Birth of canaloplasty and the concept behind it

As our understanding of glaucoma has evolved, we have come to appreciate that it involves a pathophysiology of the entire outflow pathway. Canaloplasty began as part of the movement to microinvasive glaucoma surgery and was introduced by Robert Stegmann, MD, whose procedure involved ab externo insertion of a rigid metal cannula, followed by injection of high-molecular-weight sodium hyaluronate into the Schlemm canal.¹

This concept was revolutionary because it built on the concept that the resistance to outflow in glaucomatous eyes occurs not only at the trabecular meshwork (TM), but also at the Schlemm canal and the collector channels. Cha et al showed that up to 90% of collector channels are blocked with herniated TM tissue in glaucomatous eyes.²

During the past several years, a plethora of procedures have been proposed and occasionally grouped under the designation of “viscoelastic delivery procedures,” but canaloplasty is more than that. Canaloplasty involves the combination of microcatheterization and viscodilation. The process of 360° catheterization of the Schlemm canal results in mechanical relief of microadhesions within the canal. It further works by pushing out the trabecular meshwork herniations, removing or reducing the outflow resistance in these areas.

The second step is the pressurized injection of a high-molecular-weight ophthalmic viscosurgical device (OVD), which further stretches the trabecular plates of the TM while simultaneously dilating the Schlemm canal and the collector channels.^3-5 This viscoelastic material remains for a period of time after the procedure, further facilitating the newly enhanced outflow.

Thus, an important point to remember is that canaloplasty is not simply focal injection of viscoelastic. Catheterization and viscodilation optimally address the entire canal. An early study by Smit et al suggests that dilation of the Schlemm canal can only extend circumferentially 6 mm to 14 mm beyond the point of OVD delivery.⁵ Therefore, to effectively treat the entire outflow pathway, delivery of the OVD would be required along the full 360 degrees of the Schlemm canal.

OVDs: What, how, and why?

Depletion of hyaluronic acid in the TM has been linked to primary open-angle glaucoma (POAG).² Reduced hyaluronic acid levels can lead to downregulation of matrix metalloproteinases and disruption of the extracellular matrix, leading to pathologic changes that increase outflow resistance.^6,7 During canaloplasty, the delivery of synthetic hyaluronic acid via injection of the OVD helps restore the levels of hyaluronic acid within the TM, reversing these pathological changes and removing outflow resistance.

Moreover, the pressurized delivery of the high-molecular-weight OVD not only breaks the adhesions in the canal, but also results in an amount of OVD entering the collector channels, also stretching and relieving blockage throughout the distal outflow system.

Extending the same concept, it is safe to assume that the more volume of OVD injected, the more stretching of the outflow system that will occur, resulting in a greater improvement in outflow facility.

Currently 2 devices are on the market to perform canaloplasty: the iTrack microcatheter (Nova Eye Medical), which delivers +100 μl of OVD over 360 degrees of the canal; and the Omni Surgical System (Sight Sciences), which delivers 5.5 μl of OVD across 180 degrees of the canal (twice for a total of 360 degrees and 11 μl) and is coupled with trabeculotomy as per the 510(k) clearance. Another device, the Streamline Surgical System (New World Medical), delivers 7 μl of OVD per application8 for several applications nasally but cannot be included under the canaloplasty definition because it does not deliver OVD over the entire 360 degrees of the canal and it does not perform microcatheterization.

Canaloplasty and its effect on the TM

The impact of canaloplasty in dilating the canal and the collector channels is well understood, but its impact on the TM is often a point of conjecture. Pressurized delivery of high-molecular-weight OVD into the Schlemm canal during viscodilation stretches the TM, possibly causing microperforations extending into the anterior chamber, improving outflow.³

The accumulation of extracellular matrix proteins and banded fibrillar elements is known to compromise the function of the TM cells.^6,7 TM endothelial cells counteract these imbalances by regulating hyaluronic acid levels within the outflow pathway.⁹ Hence, the replenishment of depleted hyaluronic acid during viscodilation may help to restore this regulatory function of TM cells. Thus, with a deeper understanding of the functioning of TM cells, it is apparent that canaloplasty has a clinically meaningful impact on the TM.

Building on the understanding of TM endothelial cell function, we can now also understand that in procedures involving excision of TM tissue, the removal of these important TM cells in patients with POAG can further hinder the regulation of hyaluronic acid levels in eyes, not only adding to the trauma of postoperative inflammation with angle scarring, but also working against improving the natural outflow mechanism.⁴

Canaloplasty: safe and effective

Several recent studies have added to the growing body of clinical evidence in support of the effectiveness of canaloplasty. Gallardo published a study highlighting 36-month effectiveness of canaloplasty as a stand-alone procedure and combined with cataract surgery performed with the iTrack canaloplasty microcatheter.

A significant reduction was noted in IOP and in the number of medications postoperatively in both groups, highlighting the clinical usefulness of the procedure.¹⁰ Khaimi published similar results with canaloplasty (iTrack) in patients with controlled POAG¹¹ and Koerber confirmed the findings of Gallardo and Khaimi, highlighting a comparable reduction in IOP and medications 48 months postoperatively with canaloplasty performed as a stand-alone procedure or with cataract surgery.¹² In the GEMINI study, which examined 12-month outcomes of 360° canaloplasty and 180° trabeculotomy using the Omni Surgical System with phacoemulsification, 84.2% of eyes achieved IOP reductions greater than 20% from baseline and 80% of eyes were medication free, further highlighting the usefulness of canaloplasty as a treatment modality for POAG.¹³

There is renewed interest in canaloplasty because it treats the entire outflow pathway and allows surgeons to target underlying patient physiology—not work around it. It does so without a stent and without removing or tearing precious ocular tissue.

However, to be “real” canaloplasty, the procedure must combine the mechanical breakdown of adhesions via microcatherization with the restorative and hydrostatic effect of viscodilation. When done correctly, canaloplasty offers prolonged IOP lowering in POAG with an excellent safety profile.

Robert J. Noecker, MD, MBA

E: noeckerrj@gmail.com

Noecker is a professor and a tertiary glaucoma expert specializing in the medical, laser, and surgical management of glaucoma and cataracts. He performs advanced procedures for complex glaucoma as well as laser-assisted cataract surgery combined with microinvasive glaucoma surgery for patients with cataracts and glaucoma. Noecker has no financial or proprietary interests or public or private support to disclose about the products mentioned in this article. He is a consultant to Nova Eye Medical.

References

1. Stegmann R, Pienaar A, Miller D. Viscocanalostomy for open-angle glaucoma in Black African patients. J Cataract Refract Surg. 1999;25(3):316-322. doi:10.1016/s0886-3350(99)80078-9

2. Cha EDK, Xu J, Gong H. Variations in active areas of aqueous humor outflow through the trabecular outflow pathway. Invest Ophthalmol Vis Sci. 2015;56(7):4850. Accessed November 17. 2022. https://iovs.arvojournals.org/article.aspx?articleid=2334833

3. Grieshaber MC, Pienaar A, Olivier J, Stegmann R. Clinical evaluation of the aqueous outflow system in primary open-angle glaucoma for canaloplasty. Invest Ophthalmol Vis Sci. 2010;51(3):1498-1504. doi:10.1167/iovs.09-4327

4. Fellman RL, Grover DS. Episcleral venous fluid wave in the living human eye adjacent to microinvasive glaucoma surgery (MIGS) supports laboratory research: outflow is limited circumferentially, conserved distally, and favored inferonasally. J Glaucoma. 2019;28(2):139-145. doi:10.1097/IJG.0000000000001126

5. Smit BA, Johnstone MA. Effects of viscoelastic injection into Schlemm’s canal in primate and human eyes: potential relevance to viscocanalostomy. Ophthalmology. 2002;109(4):786-792. doi:10.1016/s0161-6420(01)01006-5

6. Acott TS, Kelley MJ. Extracellular matrix in the trabecular meshwork. Exp Eye Res. 2008;86(4):543-561. doi:10.1016/j.exer.2008.01.013

7. Acott TS, Kelley MJ, Keller KE, et al. Intraocular pressure homeostasis: maintaining balance in a high-pressure environment. J Ocul Pharmacol Ther. 2014;30(2-3):94-101. doi:10.1089/jop.2013.0185

8. Lazcano-Gomez G, Garg SJ, Yeu E, Kahook MY. Interim analysis of STREAMLINE surgical system clinical outcomes in eyes with glaucoma. Clin Ophthalmol. 2022;16:1313-1320. doi:10.2147/OPTH.S358871

9. Knepper PA, Goossens W, Hvizd M, Palmberg PF. Glycosaminoglycans of the human trabecular meshwork in primary open-angle glaucoma. Invest Opthalmol Vis Sci. 1996;37(7):1360-1367.

10. Gallardo MJ. 36-month effectiveness of ab-interno canaloplasty standalone versus combined with cataract surgery for the treatment of open-angle glaucoma. Ophthalmol Glaucoma. 2022;5(5):476-482. doi:10.1016/j.ogla.2022.02.007

11. Khaimi MA. Long-term medication reduction in controlled glaucoma with iTrack ab-interno canaloplasty as a standalone procedure and combined with cataract surgery. Ther Adv Ophthalmol.2021;13:251584142110457. doi:10.1177/25158414211045751

12. Koerber NJ, Ondrejka S. Four-year efficacy and safety of iTrack ab-interno canaloplasty as a standalone procedure and combined with cataract surgery in open-angle glaucoma. Klin Monbl Augenheilkd. Published online April 14, 2022. doi:10.1055/a-1737-4149

13. Gallardo MJ, Pyfer MF, Vold SD, et al; GEMINI study group. Canaloplasty and trabeculotomy combined with phacoemulsification for glaucoma: 12-month results of the GEMINI study. Clin Ophthal.2022;16:1225-1234. doi:10.2147/OPTH.S362932