Several years ago, a pair of senior engineers from Minneapolis with expertise in fluid dynamics and a product portfolio that included pioneering work in cardiology contacted me with a novel idea for a microstent for minimally invasive glaucoma surgery (MIGS). I was intrigued by their concept, since the stent utilizes the natural outflow system of Schlemm’s canal, much like a coronary stent treats diseased vessels of the heart, and does so with an intuitive, less-invasive approach. We embarked on an important series of basic science evaluations confirming its design and mechanisms, and several years later, the Hydrus Microstent (Ivantis), the first intracanalicular stent for Schlemm’s canal, was developed.

The Hydrus is an 8-mm long, flexible, biocompatible microstent manufactured from nitinol, a nickel titanium alloy that has been used widely in a broad array of implantable medical device technologies. It is delivered via a clear corneal incision and requires the use of a gonioscope. The Hydrus is the only device in the field that bypasses the trabecular meshwork while also dilating and scaffolding the entire nasal quadrant of Schlemm’s canal. The implantation procedure can be performed in conjunction with cataract surgery or as a standalone surgery.

The Hydrus has earned the CE Mark in Europe (2011) and TGA approval in Australia (2013). To date, more than 3,300 procedures have been performed worldwide, and about one-third of those have been standalone surgeries.

Favorable Safety Profile

Glaucoma drainage devices can be divided into two categories: those that aim to restore the natural aqueous outflow and those that bypass the natural flow path. Typically, devices that target Schlemm’s canal have a better safety profile than those that redirect the fluid into alternative flow paths.

About 80% of all patients with glaucoma have mild to moderate disease. For these patients, safety is critical. Therefore, I believe canal-based devices, which attempt to restore the natural ouflow first, will likely be preferred for this population as a front-line therapy.

Easy Access to Multiple Collector Channels

The Hydrus is the first dilating microstent that enables the surgeon to access multiple collector channels with a single implant and also augment 3 full clock-hours of Schlemm’s canal. Thus, the Hydrus obviates any need for aiming for or targeting collector channels, which can be difficult, if not impossible, to visualize through the trabecular meshwork. Because the device tracks the canal for 8 mm, surgeons can be confident the device is where they want it to be, and that they have successfully augmented the outflow system.

Clinical Trials Under Way

What I find most remarkable about the leadership at Ivantis is their commitment to evidence-based medicine. Their level 1 clinical trials are most impressive, and the Hydrus bibliography includes rigorous basic science, aqueous flow, and biocompatibility studies by renowned investigators.

The HORIZON pivotal trial, the largest FDA trial of a MIGS device to date, evaluated the Hydrus Microstent plus cataract surgery versus cataract surgery alone in 556 eyes with mild to moderate primary open-angle glaucoma (POAG). Results will be submitted to the FDA this fall, and the company anticipates receiving U.S. approval in 2018 for POAG patients undergoing cataract surgery.

The COMPARE trial is the first level 1 comparative effectiveness glaucoma study comparing two MIGS approaches, the Hydrus Microstent and two iStent Trabecular Microbypass devices (Glaukos) in phakic and pseudophakic eyes without cataract surgery. This study, recommended by the company’s scientific advisors, has enrolled 152 eyes at 12 experienced MIGS centers in eight countries. Two-year follow-up data are being collected and will be available in 2018.

The company has also established a real-world global registry, the SPECTRUM study. Approximately 50 doctors in nearly 20 countries outside the U.S. have treated more than 2,000 eyes and are using the Hydrus Microstent in a broad array of indications, all of which are approved internationally. SPECTRUM is providing a large data set of real-world use, and the company reports a remarkably high follow-up rate for a registry.

This spring, Ivantis received FDA clearance to begin a second investigational device exemption trial for the Hydrus Microstent. The SUMMIT trial, for which I am the medical monitor, is a 60-eye, single-arm study of refractory glaucoma without cataract surgery.

With the HORIZON trial and the SUMMIT trial, Ivantis is the only company that I am aware of with active FDA trials at both ends of the glaucoma severity spectrum.

Compelling Data From International Studies

The HYDRUS II trial, which was performed in Europe and for which I served as medical monitor, was designed to mirror new U.S. FDA guidelines that had just been developed for MIGS trials.¹ Researchers found that IOPs were clinically and statistically significantly lower at 2 years in the Hydrus plus cataract surgery group compared with the cataract surgery alone group, with no differences in safety. Because this study was specifically designed to closely mimic the FDA pivotal trial, the company anticipates these data will be predictive of the U.S. trial data.

Researchers in Parma, Italy, recently compared outcomes attained with canaloplasty versus the Hydrus Microstent in patients with uncontrolled IOP in primary or secondary open-angle glaucoma.² They found both canaloplasty and the Hydrus Microstent implant, in a stand-alone glaucoma surgery setting, provided significant IOP reductions, with comparable rates of clinical success and safety profiles.

Another group of researchers compared the reduction of IOP and glaucoma medications following selective laser trabeculoplasty (SLT) and standalone placement of the Hydrus Microstent.³ They found that both SLT and Hydrus implantation reduced IOP without serious adverse events. In addition, Hydrus implantation led to a reduction in medications at three times the rate of SLT.

Next-generation Device

The Hydrus Microstent is a next-generation canal device with the safety profile that surgeons expect from Schlemm’s canal devices. Published studies suggest that Hydrus may have a more potent efficacy profile, and the 3 clock-hour design provides built-in confidence that you have hit multiple collector channels. GP

**In the United States, the Hydrus Microstent is available for investigational use only.

References

1. Pfeiffer N, Garcia-Feijoo J, Martinez-de-la-Casa JM, et al. A randomized trial of a Schlemm’s canal microstent with phacoemulsification for reducing intraocular pressure in open-angle glaucoma. Ophthalmology. 2015;122:1283-1293.
2. Gandolfi SA, Ungaro N, Ghirardini S, Tardini MG, Mora P. Comparison of surgical outcomes between canaloplasty and Schlemm’s canal scaffold at 24 months’ follow-up. J Ophthalmol. 2016;2016:3410469.
3. Fea AM, Ahmed II, Lavia C, et al. Hydrus microstent compared to selective laser trabeculoplasty in primary open angle glaucoma: one year results. Clin Exp Ophthalmol. 2017;45:120-127.

Dr. Samuelson is a founding partner and attending surgeon at Minnesota Eye Consultants in Minneapolis and adjunct professor at the University of Minnesota.