On Track to Profitability, Price Target Increased (MST), page-72

The introduction of minimally invasive glaucoma surgery, commonly called MIGS, has triggered a paradigm shift in the way glaucoma is treated. Traditional surgical options, while effective and powerful, have typically been a ‘one-size-fits-all’ approach. With potentially sight-threatening complications and a prolonged recovery, they were often reserved for late in the disease process.Today, MIGS procedures allow us to individualise treatment to each patient, based on their disease stage and unique characteristics. Because these procedures are less invasive and provide a high level of safety, they permit earlier surgical intervention to preserve eyesight and reduce dependence on glaucoma medications.While much of the initial focus has been on stent-based procedures, there is increasing attention on canaloplasty, a procedure where a microcatheter is used to dilate and flush out the eye’s natural drainage channels, in effect like angioplasty for the eye. This tissue-sparing and implant-free MIGS procedure targets the entire 360° of the outflow pathway to treat all points of outflow resistance and re-establish the function of the natural conventional outflow pathway. The iTrack Advance is the latest and most advanced method of canaloplasty.This article discusses the pathophysiology of glaucoma, the unique mechanism of action of canaloplasty, the advantages of iTrack Advance, and appropriate patient selection for this procedure.Aqueous Outflow and Changes in GlaucomaIn the healthy eye, aqueous humour is continually produced by the ciliary body and this rate of production is balanced by an equal rate of aqueous humour drainage. Regulation of aqueous humour outflow is important for the maintenance of a healthy intraocular pressure (IOP). Aqueous outflow occurs through two pathways – the trabecular outflow pathway (conventional outflow) and the uveoscleral outflow pathway (unconventional outflow). The conventional outflow pathway is the major pathway and accounts for 70–95% of drainage.1 In this pathway, aqueous exits the anterior chamber through the trabecular meshwork, traversing the juxtacanalicular tissue, into Schlemm canal, the collecting channels, before entering the aqueous veins which drain into the episcleral venous system.Glaucoma represents a group of optic neuropathies characterised by the progressive degeneration of retinal ganglion cells, commonly associated with elevated IOP. In glaucoma, there is increased resistance to aqueous outflow at three primary levels:Trabecular MeshworkUp to 75% of the resistance to aqueous outflow is localised within the trabecular meshwork due to a build-up of extracellular matrix.2 In particular, resistance in the juxtacanalicular area, immediately adjacent to Schlemm canal, is believed to be increased in eyes with primary open angle glaucoma and is a major cause of reduced outflow facility.3The trabecular meshwork is not a passive filter, but instead it actively regulates aqueous dynamics.4 It has been shown that endothelial cells help regulate levels of hyaluronic acid (HA), leading to changes in outflow resistance.5 Hyaluronic acid increases the activity of matrix metalloproteinases (MMPs) which have been shown to clear the deposition of extracellular matrix in the trabecular meshwork, thus reducing resistance to aqueous outflow.6 It has been found that eyes with glaucoma have lower levels of HA compared to normal eyes.7 This is important as reduced HA levels reduce the activity of MMP-2 and MMP-9, resulting in an accumulation of extracellular matrix.8 In addition, in the absence of HA, its receptor, CD44, is converted to sCD44, which is cytotoxic to trabecular meshwork cells.9Schlemm CanalIn eyes with glaucoma, Schlemm canal is shorter, more narrowed, and often collapsed, resulting in increased resistance to aqueous outflow and reduced outflow facility.10-12Collector ChannelsLastly, herniations of the trabecular meshwork are common in eyes with glaucoma and these herniations have been shown to obstruct up to 90% of collector channels in glaucomatous eyes.12Worldwide, glaucoma is the leading cause of irreversible blindness.13 The primary treatment for glaucoma is the reduction of IOP to prevent progressive optic nerve damage and slow or halt visual field loss.The iTrack Advance by Nova-Eye (above and below).The iTrack Advance ProcedureThe iTrack Advance offers a comprehensive approach to address all three points of resistance in the conventional outflow pathway, including the trabecular meshwork, Schlemm canal, and the distal collector channels to reduce IOP and medication dependence without removing tissue or leaving behind a stent or shunt. The procedure consists of two components:360° CatheterisationAt the time of cataract surgery, or as a standalone procedure, a specially designed cannula in a preloaded injector is passed across the anterior chamber through a tiny, self-sealing clear corneal incision. The tip of the cannula is used to enter Schlemm canal and a 220-micron, illuminated flexible microcatheter is passed around the entire 360° of Schlemm canal in a single intubation.Pressurised ViscodilationAs the catheter is slowly withdrawn, precise amounts of sterile HA are injected in a process called pressurised viscodilation. The device allows the surgeon to adjust the amount of HA delivered on an individual patient basis. The procedure does not hurt and is achieved without removing or damaging tissue. The microcatheter is removed from the eye at the end of the procedure and no stent, suture, or shunt is left behind.Mechanism of Action of iTrack AdvanceThe iTrack Advance procedure treats all points of outflow resistance to re-establish natural aqueous outflow through the conventional outflow pathway. There are three mechanisms of action:MechanicalThe iTrack Advance microcatheter mechanically breaks adhesions within Schlemm canal and pushes herniations of trabecular meshwork out of collector channel ostia to re-establish natural aqueous outflow.14-16HydraulicThe process of pressurised viscodilation dilates Schlemm canal by up to two to three times14-16 and stretches the trabecular meshwork, causing microperforations into the anterior chamber.14 Additionally, the injection of viscoelastic has been shown to separate the compressed trabecular plates within the trabecular meshwork and to dilate the distal outflow system to help revive the conventional outflow pathway.14-16BiochemicalThe injection of synthetic HA during pressurised viscodilation has been postulated to improve the balance of HA levels within the trabecular meshwork. Delivering HA may increase the activity of matrix metalloproteinases which have been demonstrated to clear the deposition of extracellular matrix from the trabecular meshwork. Additionally, HA may bind to the CD44 receptor, helping to minimise the cytotoxic effect on trabecular meshwork cells.Advantages of iTrack AdvanceResistance to aqueous outflow may be located anywhere along the conventional outflow pathway and currently there is no readily available diagnostic test to identify where the location of resistance is. By treating all potential points of aqueous resistance, both proximal and distal, the iTrack Advance comprehensively addresses the entire outflow system. This is in comparison to stent-based MIGS, which are focal in their approach and only address a portion of the outflow system.The iTrack Advance is a tissue-sparing procedure. It does not damage the angle and preserves the conjunctiva, leaving all future treatment options available. Removal of tissue from the angle can cause inflammation, bleeding, and post-operative scarring. Given the important role of the trabecular meshwork in regulating aqueous dynamics and levels of HA, it may be prudent to preserve angle tissue, especially in younger patients. This leaves all future options available, including repeat canaloplasty, insertion of a transtrabecular stent, and selective laser trabeculoplasty. When performed via an ab-interno approach, the iTrack Advance preserves the conjunctiva, which is important should future filtration procedures be required in a patient’s lifetime.The iTrack Advance offers excellent endothelial safety. By restoring aqueous outflow over the entire 360° of the conventional outflow pathway, the procedure avoids the creation of potentially damaging preferential flow to one or more focal points, helping to reduce the risk of endothelial cell loss. As there is no device left in the eye, there is no risk of mechanical damage to the corneal endothelium. Additionally, as a tissue-sparing procedure, there is no removal of tissue that could cause post-operative inflammation and subsequent endothelial injury.Finally, the unique design of the fibre-optic microcatheter allows for cannulation of the entire 360° in one pass, simplifying the procedure and reducing the degree of intra-operative manipulation. The illuminated tip provides the surgeon with continuous feedback and visualisation of the tip to ensure accurate treatment, and the atraumatic bulbous tip is designed to prevent inadvertent false passages or cannulation of a collector channel.What Results Can Patients Expect?iTrack canaloplasty has been shown to provide excellent clinical outcomes, lowering both IOP and medication burden when performed in conjunction with cataract surgery or as a standalone procedure.17 On average, iTrack achieves a 30% reduction in IOP and a 50% reduction in the number of anti-glaucoma medications.17,18 In a study of patients with POAG, iTrack canaloplasty significantly reduced IOP from 20.5 ± 5.1mmHg at baseline to 13.3 ± 2.1mmHg at 36 months.17 This was accompanied by a reduction in medications from 2.8 ± 0.9 pre-operatively to 1.3 ± 1.3 medications over the same time period.17 At 36 months, 95.5% of eyes had an IOP ≤ 17mmHg and 68.2% of eyes were on ≤ 1 medication.17 No serious intraoperative or postoperative complications were reported.17 Results are comparable when used as a standalone procedure or when combined with cataract surgery.17 For patients with POAG controlled on eye drops, iTrack canaloplasty, as standalone and combined with cataract surgery, has been shown to lead to a sustained reduction in medication burden.19 In a single-centre retrospective case series, 56% of eyes were medication free at 36 months.19What Are the Risks?Because the iTrack Advance procedure does not damage or remove tissue, and no implant is left behind, it provides a high level of patient safety. The procedure is very safe for the cornea and studies have shown that the rate of endothelial cell loss is comparable to cataract surgery alone. Adverse events are infrequent and generally self-resolving without sequalae. The most common adverse event is reflux of blood from Schlemm canal into the anterior chamber, causing a microhyphaema which usually resolves within a few days to a week. Other common risks include IOP spikes, which are also seen with other MIGS procedures and even cataract surgery alone. However, compared to conventional glaucoma procedures, the iTrack Advance is associated with fewer risks, both in number and severity. Should iTrack not work, it does not preclude any other form of glaucoma treatment. If the procedure is not successful, medication, selective laser trabeculoplasty, another MIGS procedure or conventional glaucoma surgery are all potential options.Which Patients May Benefit from iTrack Advance?iTrack Advance is an effective treatment option in both phakic and pseudophakic patients with mild-to-moderate primary open angle, pseudoexfoliative, or pigmentary glaucoma. For these patients, iTrack Advance has been clinically proven to lower IOP and reduce, and often eliminate, the need for glaucoma medication. It is particularly suited for patients who are intolerant to glaucoma medications, have difficulty taking them as prescribed, or in whom medications are not lowering IOP sufficiently.For patients with advanced glaucoma controlled on drops, iTrack can be performed ab-interno or ab-externo as a bleb-free alternative to trabeculectomy.