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Santen Vision 2030

MicroShunt pending FDA approval exemplifies new focus on unmet patient need

Howard Larkin

Posted: Thursday, October 1, 2020


Omar Sadruddin MD

Perhaps one of the most conspicuous unmet needs in ophthalmology is the gap in primary open-angle glaucoma (POAG) surgical options between minimally invasive glaucoma surgery (MIGS) for mild-to-moderate cases, and filtration surgery – with all its risks – for advanced and severe cases. There’s virtually no procedure in the middle for patients needing low-teens intraocular pressures (IOP) long-term to slow possibly decades of visual field loss.

Santen is directly targeting this gap with its PreserFlo MicroShunt, said Omar Sadruddin MD, Global Senior Medical Director of Santen Inc. First CE marked in 2012 and commercially available in Europe since late 2018, the device is now under review for approval by the US FDA. The goal is to offer a device with greater efficacy than current MIGS with a safety profile that will encourage implantation earlier than trabeculectomy.

“MicroShunt fits well with our new long-term vision through 2030 for the company,” Dr Sadruddin said. “As an organisation, our contribution to society starts by being ‘in service of patients’, and in targeting a significant unmet need MicroShunt provides great value for the patient.”

Implanted through a conjunctival/Tenon’s flap, MicroShunt is an 8.5mm tube that shunts aqueous from the anterior chamber through a 70-micron lumen into a filtration bleb. Fins on the tube help keep the shunt in place and prevent excess drainage around the device.

Early multi-centre studies show mean IOP reduction of 30-to-55%, with success rates, defined as IOP >6mmHg and <21mmHg or ≥20% IOP reduction from baseline with/without medication and no reoperation, varying from 81-to-86% at two years. (García-Feijoó J et al. Poster presented at WGC 2019.)

Indeed, one early study achieved overall success (IOP ≤14 mmHg and >20% reduction in IOP from baseline with or without meds and no reoperation) in approximately 80% of the patients at three years. Five-year results demonstrated similar IOPs, a mean of 11.4mmHg, to those reported in the three-year follow-up paper, suggesting the MicroShunt may provide long-term mid-teens IOP control. (Batlle JF et al. J Glaucoma. 2016;25:e58–65. Batlle JF et al. APAO, Bangkok, Thailand, 2019.) Six- and seven-year data are being prepared for future presentation, Dr Sadruddin said.

ANATOMY OF AN INNOVATION
Every aspect of MicroShunt reflects a spirit of innovation, right down to the material of which it is constructed. Poly(styrene-block-isobutylene-blockstyrene) (SIBS) is a novel polymer with unique elastic attributes designed specifically for long-term implantation in the body – Santen expects its inert chemical properties should allow it to last the lifetime of the patient. It was first implanted in humans as a coating on a drug-eluting cardiac stent in 1999, and has established a strong track record for long-term biocompatibility in cardiac applications (Pinchuk L et al. Biomaterials. 2008;29:448–60).

However, its long-term suitability in the eye as a glaucoma shunt has not yet been established by large-scale trials, which are ongoing, Dr Sadruddin said. “We are taking a very careful approach to generate this data and not make any claims in the meantime. The US [phase III pivotal] trial will provide good long-term data and will be mandated by the FDA. We will probably be asked to follow all patients up for five years.”

Another important feature of SIBS is it provokes minimal inflammation and encapsulation when compared with commonly used implant materials such as silicone rubber and polypropylene. The material is also thermoformable. This allows it to assume the shape of the globe without a tendency to return to its original shape. By contrast, thermoset materials such as silicone rubber tubes slowly straighten over time, requiring they be covered with a patch graft to prevent erosion. SIBS has no tendency to straighten, which should eliminate the need for a patch graft.

The MicroShunt went through three major design iterations over the course of its 20 years in development. The current device’s 70-micron lumen diameter is sufficiently large to allow passage of sloughed endothelial cells, which are approximately 40-to-50 microns in diameter, yet small enough to prevent clinically significant postoperative hypotony.

The device’s 1.1mm wingspan fin is located halfway down the tube, fixes the device in a 1mm wide scleral pocket, thereby preventing migration into the eye. The fin also prevents leakage around the tube and helps orient the device bevel-up in the anterior chamber (AC), preventing the lumen from being blocked by debris or iris tissue.

When correctly placed, the distal end of the MicroShunt is located 6.0mm posterior to the limbus. This placement directs aqueous humour more posteriorly than trabeculectomy, which may eliminate the thinner-walled anterior blebs that can occur with trabeculectomy.

Research is ongoing into how the MicroShunt’s unique posterior bleb, which tends to vascularise while remaining functional and usually remains flat out to three years or more, responds over the long term, Dr Sadruddin said. “As one of our investigators stated, this is not your grandfather’s bleb”, alluding to unique characteristics of a MicroShunt bleb, which is very different than trabeculectomy blebs and understanding this better should provide surgeons with a visual cue on functionality. Studies of how the device might affect corneal endothelial cells in the long term are also under way.

IMPLANTATION
The MicroShunt’s length was designed to allow it to be positioned through a 3mm-long scleral needle tunnel with the outflow end above the scleral surface behind the excursion of the upper eyelid, which minimises potential erosion. Positioning the device to the temporal or nasal side also minimises the risk of damaging the superior rectus muscle while preserving the other side for possible future filtration procedures, if needed.

Implantation is less invasive compared with trabeculectomy, Dr Sadruddin pointed out. An approximately 5-6mm-wide fornix-based conjunctival/ Tenon’s flap is created, followed by formation of a deep sub-Tenon’s pocket of 6.0-to-8.0mm. Wet field cautery is applied to prevent bleeding. Several corneal LASIK shields soaked in mitomycin C are placed within the flap for two-to-three minutes, after which they are removed and the ocular tissue rinsed with balanced saline solution (BSS).

After marking the sclera 3mm from the limbus, a 1mm-deep scleral pocket is made using a triangular knife. A 25-gauge needle is introduced into the pocket and a scleral needle track is created into the AC. The MicroShunt is inserted through the pocket and track, bevel-up, into the AC. When correctly placed, the MicroShunt should bisect the angle without touching the endothelium or the iris. The fin is tucked in the scleral pocket. After flow is established, Tenon’s and conjunctiva are pulled up, avoiding tucking the distal end of the tube into Tenon’s capsule, and sutured watertight.

MicroShunt is designed for POAG patients whose IOP is not well controlled on maximum tolerated meds, Dr Sadruddin said. But if the ease of earlier intervention and long-term efficacy pan out, the definition of maximum meds may change from three or more to two – particularly given there is ample research suggesting that adding more meds don’t necessarily lower pressures significant for a long duration.

While implantable with or without cataract surgery, Dr Sadruddin sees glaucoma specialists as the primary target clinicians due to the need to manage the bleb. He sees MicroShunt as another tool in the armamentarium for customising treatment. “If you want an IOP <15mmHg for your patient, and the only remaining options are trab or tubes, MicroShunt may be a reasonable alternative.”

Santen offers a structured course for implanting the device that includes didactic material, virtual simulator and wet labs, as well as supervised procedures. Dr Sadruddin credits having a standardised technique to the users of the product and their willingness to share nuances and pearls of the procedure with new users. “By having created a community of MicroShunt users, we continuously focus on ways to optimise the technique and bring that education to current and future users of the MicroShunt.”

He acknowledged, however, that more long-term studies need to be done to validate the device performance and clinical results. These may include remote sensor studies to monitor IOP 24 hours a day.

“We have made strategic investments in companies looking at sensors. It’s a way to provide more feedback to surgeons to create better management plans, which allows to preserve as much of the patient’s vision as possible,” Dr Sadruddin said. It’s another way Santen is innovating in service of patients.