Clinical trial • Drug-eluting stent • Food and Drug Administration • Investigational device exemption • Medicine

Fabric and design of the MicroShunt

The MicroShunt is made from SIBS (Fig.2) [7], which is synthesized by a living cationic polymerization technique [8, sixteen]. The inert, soft, and flexible thermoformable elastomeric backdrop of SIBS enable the MicroShunt to adapt to the curvature of the eye [17].

In preclinical studies, SIBS demonstrated biostability in the eye, with a lack of biodegradation byproducts, resulting in reduced chronic inflammation and minimal scar formation [17]. In 2003, Dr. Jean-Marie Parel and his team at the Bascom Palmer Middle Institute OBC laboratory conducted a written report comparing the furnishings of silicone tubes versus SIBS implants in the corneal stroma and sub-Tenon’south space of New Zealand White rabbit eyes [8, 17]. SIBS implants were constitute to be biocompatible in the rabbit model and maintained 100% catamenia patency at half-dozen months [17]. Results showed reduced collagen deposition in the SIBS group compared with the silicone group; furthermore, myofibroblasts were not observed in tissue surrounding the SIBS implants, whereas silicone implants were shown to induce expression of cellular components responsible for scarring [17].

These positive preclinical findings demonstrating SIBS biocompatibility in ophthalmology are in line with real-earth experience with SIBS in cardiology. The SIBS-coated TAXUS® (Boston Scientific Corporation, Natick, MA, USA) is a cardiac stent that releases the antiproliferative drug paclitaxel in the coronary artery every bit a means of minimizing restenosis [xviii]. TAXUS® has been implanted in more than a million patients worldwide, with a well-established safe profile [8, 18]. In vitro and in vivo studies of the TAXUS® cardiac stent have confirmed no biodegradation and minimal inflammation, highlighting the versatility of SIBS as a biocompatible polymer [nineteen].

The MicroShunt is an 8.5 mm-long (350 μm outer diameter; 70 μm lumen) surgical device that has been designed for implantation in glaucomatous optics to reach the desired pressure range by draining the aqueous humor from the inductive chamber through the sclera to under the conjunctiva and Tenon’s capsule to form a bleb (Fig.iii) [seven]. The length of the device was designed to let it to be positioned through a 3 mm-long scleral needle tunnel with the outflow end above the scleral surface behind the circuit of the upper eyelid [ix]. The lumen size was approximated using the Hagen-Poiseuille equation for laminar menstruation (Fig.iv) [vii] and was optimized in a rabbit eye implant study [twenty]. The rabbit heart implant study conducted past Arrieta et al. investigated SIBS implants with differing internal lumen diameters (70, 100, and 150 μm) in New Zealand White rabbit eyes and ended that 70 μm and 100 μm SIBS implants resulted in fewer mail service-operative complications compared with the 150 μm implant [20]. The study also ended that a lumen diameter of lxx μm was found to exist adequate to prevent chronic hypotony [20], while also being sufficiently large to prevent bottleneck (the lxx μm diameter of the lumen is larger than the 40–50 μm diameter of a sloughed endothelial prison cell) [seven].

Dimensions of the MicroShunt and placement in the eye. (Adjusted from Pinchuk 50, et al. Regen Biomater. 2016;3:137–42 [7].)

Located halfway downward the MicroShunt is a 1.1 mm wingspan fin (Fig.
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three) that sits within a shallow pocket in the sclera [seven, 9]. The fin prevents migration of the device into the eye [7], holds the device in the pocket, preventing any peri-annular leakage [9], and orients the device into the correct position, with the bevel facing the cornea, to enable clearance of debris if the lumen entrance becomes blocked [7].

Surgical implantation of the MicroShunt

The MicroShunt drains aqueous humor from the anterior bedroom to a bleb formed under the conjunctiva and Tenon’south capsule [vii]. The subconjunctival fluid collected within the bleb is resorbed either directly into the episcleral venous system [vii], into the tear film via microcysts (naturally occurring channels in the conjunctiva) [7, 21], or via orbital lymphatics [22, 23]. Drainage of aqueous sense of humor through this route by the MicroShunt bypasses high resistance in the trabecular meshwork, as well as Schlemm’s canal, the collector channels, and the scleral venous plexus [7, 8].

The surgical procedure for the MicroShunt (illustrated in Fig.5) is minimally invasive (relative to trabeculectomy), and the device is implanted via an ab externo approach [7, 9, 24].

Surgical procedure for MicroShunt implantation. (Adapted from Pinchuk L, et al. Regen Biomater. 2016;3:137–42 [7].) ane. Anesthetic is administered beneath the conjunctiva (anesthetic tin can be injected locally or every bit a peribulbar block, or practical topically); 2. An incision is made parallel to the limbus and under Tenon’south capsule; 3. Blunt scissors are used to dissect the Tenon’s from the sclera over one to 2 quadrants and deep to the equator; four. Following hemostasis using bipolar diathermy (non shown), MMC-soaked sponges are placed in the pocket, which is then rinsed with sterile saline solution; v. A 1 mm-wide, ane–ii mm-long shallow scleral pocket is made iii mm posterior to the limbus; 6. A needle is passed through the scleral pocket into the anterior chamber, approximately bisecting the cornea and iris at the level of the trabecular meshwork;^a
7. The MicroShunt is threaded through the pocket and needle tunnel with forceps, and the fins of the device are wedged into the scleral pocket; 8. The flow of aqueous sense of humor from the anterior chamber to the flap is confirmed past drop observation; 9. The distal end of the device is tucked beneath the conjunctiva and Tenon’southward capsule which are then pulled over the MicroShunt and sutured back to the limbus with 10–0 nylon sutures
^aThis stride is consistent with the European union labeling; in the USA, a double-footstep pocketknife is used instead of a needle to create the tunnel into the anterior chamber [13].
MMC = Mitomycin C.

A fornix-based subconjunctival and sub-Tenon’s flap is dissected at the nasal or temporal quadrant over a circumference of 90 to 120 degrees, to at least 8 to 10 mm posterior to the limbus. Post-obit placement of MMC-soaked sponges in the flap for 2 to iii min of exposure, a 3 mm marker is used to mark a signal 3 mm from the middle border of the surgical limbus in the blue-grey zone. At the distally-marked signal on the sclera, a 1 mm width knife is used to incise a shallow triangular pocket in the sclera (big enough to seat the fins of the MicroShunt). A needle is then used to create a transscleral tunnel from the apex of the scleral pocket into the anterior chamber. Using forceps, the MicroShunt is threaded, bevel up and fins flat, into the transscleral tunnel. The fins are then wedged into the scleral pocket. It is important that flow through the MicroShunt is checked prior to closure of Tenon’s sheathing and the conjunctiva. Menses is confirmed visually by beginning observing a percolation of air and aqueous humour from the distal terminate of the device. One time air is purged from the tube, a drop of aqueous sense of humour volition slowly grow on the distal finish of the device. Equally the volume of the driblet increases, period could be erroneously perceived as decreasing; even so, book increases to the third power of flow and and so flow is difficult to judge when the drop is too large. It is prudent to wipe the drop abroad at times with a sponge and visualize a pocket-size drib to confirm flow. The IOP should and then exist estimated at equilibrium flow to be about half-dozen mmHg or less, which can be effectuated by depressing the central cornea with a 30-One thousand cannula. If flow through the lumen is not observed, then the following troubleshooting procedures can exist performed: 1) ensure that the entrance to the MicroShunt is complimentary of debris and not lodged in the iris or cornea; 2) increase IOP by injecting BSS through a paracentesis in the clear cornea; 3) use a 30-G cannula and inject BSS through the lumen of the MicroShunt to discharge air and prime the device; four) bank check for fluid menstruation around the device as, if the fins are not seated correctly, the path of least fluid resistance tin exist effectually the MicroShunt instead of through the lumen of the device; 5) withdraw the MicroShunt slightly in the event that the fins are wedged too tightly in the pocket thereby constricting the lumen and preventing menstruum; 6) remove the MicroShunt and place in a new needle tunnel; 7) if none of these procedures initiate flow, remove the device and supercede with a new MicroShunt. Post-obit confirmation of flow, the distal end of the MicroShunt is tucked underneath Tenon’southward capsule and the conjunctiva, ensuring that it is straight and free of tissue; sutures are then used to reposition Tenon’due south capsule and the conjunctiva over the device and to the limbus [7, 9, 13].

It is of note that implantation of the MicroShunt can be performed in combination with cataract surgery, or as a standalone procedure [9]; furthermore, the implantation procedure does not crave intraoperative gonioscopy, sclerostomy, or iridectomy [8, 25].

Traditional glaucoma-filtering surgeries routinely apply MMC, and a Cochrane review confirmed that MMC is able to reduce the adventure of failure in trabeculectomy [26]. This agent inhibits the proliferation of cells that form scar tissue [26, 27]; adjunctive application of MMC afterward filtering surgery, with or without needling, is performed to attenuate mail-operative subconjunctival fibroblast proliferation and suppress excessive bleb scarring [27]. Intraoperative use of MMC has also been shown to reduce the risk of surgical failure and increase the surgical success rate in minimally invasive devices, including the MicroShunt [8]. Various MMC concentrations and application times have been used in glaucoma filtration surgery; a dose-response relationship, although observed in some studies, has not always been reported [28]. Concentration and application time of MMC during implantation of the MicroShunt vary in the literature; concentrations of 0.ii–0.4 mg/mL and application times of 2–3 min have been reported [7–9].

Clinical evaluation of the MicroShunt

Iii clinical studies have been completed, and a farther study is ongoing, assessing the long-term rubber and efficacy of the MicroShunt (Table1) [ten–thirteen].

Key data from a MicroShunt clinical study

In a prospective, single-arm study conducted in the Dominican Republic ({"blazon":"clinical-trial","attrs":{"text":"NCT00772330","term_id":"NCT00772330"}}NCT00772330), the MicroShunt was implanted with MMC (0.iv mg/mL for three min) in 23 patients with principal open-angle glaucoma [nine]. Of these patients, 14 received the MicroShunt alone, and ix received the MicroShunt in combination with cataract surgery [9]. Three-year outcomes of the study are summarized in Table2.

A similar IOP reduction was observed in patients who received the MicroShunt solitary and in patients who received the MicroShunt in combination with cataract surgery (Fig.6) [nine]. At the Year ii visit, at that place were ii optics that did not demonstrate an IOP of ≤14 mmHg and ≥ 20% reduction in IOP from baseline (having an IOP of xviii and xix mmHg, respectively); at Yr 3, only 1 eye did not come across the criteria for qualified success (with an IOP of 16 mmHg) [ix]. I eye required reoperation [9]. At Twelvemonth iii, the overall hateful reduction in glaucoma medications was 71%, with 64% of patients no longer taking IOP-lowering medication [ix].

Mean medicated IOP levels from baseline up to Year 3. (Adapted from Pinchuk L, et al. Regen Biomater. 2016;3:137–42 [7].)
n = 9 from baseline to Years 1, 2, and 3 for MicroShunt process with cataract surgery;
northward = 14, 13, and 13 from baseline to Years 1, two, and 3, respectively for MicroShunt process without cataract surgery.
IOP = intraocular pressure.

Twenty-one post-operative AEs were noted in seven patients. Two of the vii patients experienced multiple AEs, including transient hypotony, shallow anterior sleeping room, iris touch, and choroidal detachment [9]. The most common complications were transient hypotony (IOP < 5 mmHg after Day ane, which resolved past 24-hour interval 90; xiii%); shallow anterior chambers (xiii%), which occurred during the starting time 3 weeks after surgery; device touching the iris (13%); hyphema (9%); exposed Tenon’s sheathing (9%); and transient choroidal detachment (ix%) [ix]. All complications were transient, occurring inside the first 3 months afterwards surgery, and resolved spontaneously [9]. No cases of erosion, device migration, leaks, infections, or persistent corneal edema were observed up to 3 years after implantation [9].

The MicroShunt implantation process was refined to provide less problematic blebs that are diffuse and posterior as a result of a wide and deep fornix-based subconjunctival/Tenon’southward pocket and wide placement of MMC [9]. In Batlle et al. 2016, the typical bleb appearance tended toward shrinkage in volume and increased vascularity with time [9]. One case of an encysted bleb was observed, only controlled IOP was achieved subsequently bleb revision [9]. 1 patient underwent reoperation with a second MicroShunt at 27 months due to an encapsulated bleb; the outset device remained in place [9]. This patient’s treatment was considered a failure; however, the data were not excluded from the study [9].