38 Translimbal SIBS Shunt: The InnFocus MicroShunt A 12-year-old Asian-American girl with mild-to-moderate juvenile primary open-angle glaucoma (POAG) presented for a surgical consultation. Her initial baseline intraocular pressure (IOP) was 25 mm Hg OD and 30 mm Hg OS. She was started on topical latanoprost 0.005% at bedtime in both eyes, and fixed combination brinzolamide 2% and timolol 0.5% twice daily in both eyes. Her medical history is positive for nail-patella syndrome (also known as hereditary onycho-osteodysplasia [HOOD] syndrome), an autosomal dominant syndrome characterized by abnormalities of the nails, knees, elbows, and pelvis. It is also associated with elevated IOP and renal disease. Her best corrected visual acuity was 20/20 OU with myopic correction –5.25 D OD and –5.75 D OS. The IOP was 14 mm Hg OD and 11 mm Hg OS on medication. She had a mild posterior subcapsular cataract in both eyes. Her optic nerve cup-to-disk ratio was 0.75 OD with a superior notch, and 0.85 OS with superior rim thinning. The visual fields revealed a superior and inferior nasal defect in the right eye (–3.09 mean deviation) and an inferior nasal defect in the left eye (–3.61 mean deviation). The corneal thickness was 612 µm OD and 619 µm OS. Three months later, the IOP rose to 26 mm Hg OU, with some question as to patient compliance with medication. Over the next 6 months, different topical glaucoma medications were used, including bimatoprost 0.01%, the fixed combination brimonidine 0.2%–timolol 0.5%, and the fixed combination dorzolamide 2%–timolol 0.5%. Despite this, IOP the remained in the range of 21 to 26 mm Hg. The patient underwent trabeculotomy ab interno with the Trabectome in the left eye, which initially controlled the IOP in the mid-teens, but it quickly rose to preoperative levels within 2 months. Alternative glaucoma surgeries were discussed, including trabeculectomy, glaucoma aqueous tube shunt, and the newer investigational subconjunctival filtration techniques. The patient underwent transconjunctival gel implant with the XEN implant (AqueSys Inc., Aliso Viejo, CA; Allergan, Irvine, CA) in the left eye, but with conjunctival dissection and partial tenonectomy and application of mitomycin due to concerns about scarring. After initial hypotony, the IOP rose to the mid-20s after 2 months, with peripheral anterior synechiae covering the internal portion of the implant. The synechiae were lysed with neodymium:yttrium-aluminum-garnet (Nd:YAG) laser and the IOP stabilized to the low teens with dorzolamide-timolol twice a day. Because of these issues in the left eye, the right eye underwent surgery with the InnFocus MicroShunt® (InnFocus, Miami, FL), also with partial tenonectomy and application of mitomycin. After hypotony in the range of 3 to 5 mm Hg for the first 6 weeks, the IOP stabilized at 8 to 11 mm Hg on no glaucoma medications. At the 5-month postoperative visit, the topical steroid was tapered off, with an IOP of 10 mm Hg, visual acuity 20/25, and a low diffuse bleb. The InnFocus MicroShunt is one of several products that originated from a 10-year quest to develop a novel synthetic biomaterial that would resist biodegradation, inflammation, and encapsulation in the body. The key feature in the material used in this stent is a base co-polymer called polyisobutylene, shown in the central block of the tri-block polymer in Fig. 38.1. Polyisobutylene itself is a gum resembling chewing gum. The triblock polymer, poly (styrene-block-isobutylene-block-styrene) or “SIBS” is shown in Fig. 38.1 where N is an integer greater than M.1–4 The first medical use of SIBS was for Boston Scientific Corporation’s (Natick, MA) TAXUS® stent.5,6 TAXUS is a small balloon-expandable metallic stent (2 to 3 mm in diameter and 10 to 20 mm long), with a SIBS coating that slowly releases the antiproliferative drug paclitaxel into the wall of the coronary artery to prevent restenosis. Data collected from studies of TAXUS confirmed no biodegradation and minimal tissue reaction.7 Histopathology results 2 months after implantation of rabbit studies with the first generation were reported by Parel et al8 and Acosta et al.9 They found that there were no myofibroblasts or angiogenesis in the vicinity of the SIBS disks, nor were there integral capsules surrounding the disks. In contrast, the silicone rubber controls showed angiogenesis, myofibroblasts, and significant capsules attached to the disks. In summary, SIBS was found to be totally innocuous in the eye. Shortly thereafter, it was decided that a glaucoma drainage device without a plate might be achievable if the tube did not occlude. This would require that the lumen of the tube be larger than the diameter of a sloughed endothelial cell, which is about 40 to 50 µm, while at the same time sufficiently small to prevent hypotony. The lumen size was approximated from the Hagan-Poiseuille equation, and a series of rabbit eye implants by Arrieta et al10 confirmed that a lumen diameter of approximately 70 µm would satisfy these requirements.11 Another issue was the placement of the tube. It was decided that draining to a flap under the conjunctiva and Tenon’s capsule, much like the gold-standard trabeculectomy, made the most sense. The advantage of the MicroShunt would be the avoidance of cutting the sclera and suturing the scleral flap with sutures placed under the proper tension to control outflow, a process that requires significant surgical skill. In addition, the fluid dynamics of the MicroShunt could be controlled by the lumen diameter and length to minimize hypotony. And so began the development of a SIBS-based microshunt.12,13 There were three major iterations of shunt design (Fig. 38.2) with varied dimensions (Table 38.1). These three iterations were tested first in chronic rabbit eye studies at the University of Miami, Bascom Palmer Eye Institute Ophthalmic Biophysics Center (OBC) laboratory, and then in pilot feasibility studies over a period of 4 years to determine the best design as well as the best implant technique. All animal studies were authorized by the University of Miami Animal Care and Use Committee. All feasibility studies in humans were authorized by the appropriate government ethics committees. In France, approval was granted by AFSSAPS (Agence Française de Sécurité Sanitaire des Produits de Santé) and later by ANSM (Agence Nationale de Sécurité du Medicament et des Produits de Santé). In the Dominican Republic, approval was granted by CONABIOS (the Dominican Republic National Counsel of Bioethics and Health). Local hospital-based ethics committee approvals were also obtained where necessary. Table 38.2 summarizes the baseline characteristics, changes in IOP, and glaucoma medication use at 1 year. The major criterion for qualified success, adopted from the Tube Versus Trabeculectomy (TVT) study,14 is IOP ≤ 21 mmHg with a reduction from baseline of ≥ 20% with or without glaucoma medication and with no further incisional procedure. The first-generation product was a SIBS tube (Fig. 38.2a) with a 1 mm × 1 mm SIBS tab jutting out of one side. It was called the MIDI-Tube (minimally invasive drainage implant). The purpose of the tab was to prevent migration of the shunt into the anterior chamber due to movement caused by globe rotation and blinking. The reason the tab was attached to one wall of the shunt, and not symmetrical about the tube, was that the device was delivered through a slotted needle inserter, in which the tab jutted out of the slot in the needle. Professor Isabelle Riss, formerly at the Hôpital Pellegrin in Bordeaux, France, and currently at Pôle Ophtalmologique de la Clinique Mutualiste, Pessac, Cedex, France, was the first surgeon to implant the MIDI-Tube in humans in January 2006. Twenty-four advanced cases, with about half of the eyes failing previous trabeculectomy, were used in the Bordeaux I study (Table 38.2). Mitomycin C (MMC) was not used intraoperatively, and the qualified success rate was 42% at 1 year. In addition, there were two occurrences of erosion (successfully patched) of the sharp corner of the tab through the conjunctiva in two patients who were extreme myopes (eye was elongated and the conjunctiva stretched thin). It was concluded that MMC would be required in this patient population to sustain the bleb and that the tab needed to be redesigned to be less erosive. It was also found that the slotted needle inserter was unreliable, as the device, being very soft and somewhat sticky, often jammed in the inserter; it was more reliable to insert the device with a forceps through a preformed needle tract than to push it through a nonlubricated tube. A second clinical study (Bordeaux II study) of the same MIDI-Tube design was initiated in 16 patients with the application of low-dose MMC in the subconjunctival/Tenon’s flap as a means of controlling healing of the conjunctiva to the sclera and loss of the bleb. MMC was applied to the scleral side of the flap only using two or three Schirmer strips, which are sponge-like strips used to absorb and measure teardrop quantity. The dose consisted of a total of approximately 0.6 mL of a 0.2 mg/mL concentration applied for 2 to 3 minutes, and the MMC was flushed from the eye with 250 mL of sterile saline. The success rate increased to 67% at 1 year in these late-stage refractory patients. These data confirmed that MMC needs to be used in conjunction with a redesigned MIDI-Tube tab in these late-stage patients. (The Bordeaux II study was in progress when the erosions were noted from the sharp tab in the Bordeaux I study.) Nine months into the Bordeaux II study, InnFocus decided to test in parallel an alternate model called the MIDI-Ray (Fig. 38.2b), which was a SIBS tube (outer diameter 350 µm, lumen diameter 100 µm) with a 7-mm-diameter SIBS plate that was 350 µm thick. The device resembled a stingray; hence its name. The hypothesis was that the lack of encapsulation of the SIBS plate would facilitate fluid percolation through the sclera as well as reduce problems associated with motility and diplopia, often encountered with the large plate valves.15 It would also obviate the need to use MMC. A 12-subject clinical study was initiated by Juan F. Batlle Pichardo in September 2007 at Centro Laser, Santo Domingo, Dominican Republic. Unfortunately, the lack of capsule formation around the MIDI-Ray SIBS plate resulted in a thin conjunctiva, which led to cystic-type blebs and a qualified success rate of only 58%. In addition, the 100-µm lumen resulted in a high incidence of acute hypotony (all cases resolved spontaneously), in which case the investigator tied off the tube with a suture until the device healed in the eye. (Tying off tubes is often practiced with the large drainage tubes such as the Baerveldt valve.) As the data accumulated from the Bordeaux II study, showing a 67% success rate without a plate, with low-dose MMC and with no hypotony, it was decided to continue with a plateless tube, modify the tab to make it more atraumatic, and to use a broader application of MMC, which was demonstrated to be safe in the long term.16 This new design of the microshunt was initially called the MIDI-Arrow (Fig. 38.2c) as the tab was changed to an atraumatic, planar symmetrical fin-like design that resembled the feathers on an arrow. The MIDI-Arrow name was later changed to the InnFocus MicroShunt®. The lumen of the MIDI-Arrow remained at 70 µm so as to eliminate the need to tie off the tube during the healing phase. A 23-patient feasibility trial with 0.4 mg/mL MMC applied for 3 minutes was initiated in the Dominican Republic in patients of mixed race (mixture of black, white, and aborigine) with POAG and no previous conjunctival incisions, who had failed maximum tolerated glaucoma medication. These changes to the device as well as the procedure led to a qualified success rate of 100% with a 50% drop in IOP from baseline at 1 year.
Case Presentation: InnFocus Microshunt for Juvenile Open Angle Glaucoma
The Development of SIBS
The Development of the Glaucoma Device
The Four Iterations of the Glaucoma Device
Ento Key
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