Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. A Novel Schlemm’s Canal Scaffold: Histologic Observations Ian Grierson, PhD,* Hady Saheb, MD,w Malik Y. Kahook, MD,z Murray A. Johnstone, MD,y Iqbal I. K. Ahmed, MD,8 Andrew T. Schieber, MSME,z and Carol B. Toris, PhD# Purpose: To assess the biocompatibility of a novel implant made of Nitinol (nickel-titanium alloy), designed to improve aqueous humor outflow. Materials and Methods: In the first arm of biocompatibility testing, microstents were surgically inserted into Schlemm’s canal (SC) of 2 non-human primates (NHPs), and a third NHP served as a surgical sham control. After 13 weeks the animals were killed, and the eyes were examined by light and scanning electron microscopy. Two masked investigators evaluated the histology sections. The second arm utilized 8 New Zealand white rabbits; each rabbit received a microstent inserted into the sclera and subconjunctival space by means of passage across the anterior chamber thus providing contact with several representative ocular tissues. The fellow eye of each rabbit underwent a sham procedure without microstent insertion. The rabbits were killed after 26 weeks, and a trained ocular pathologist examined the specimens using light microscopy. Results: Histologic and scanning electron microscopy analysis of the NHPs demonstrated that the microstents were located in SC. There was no evidence of an acute or chronic inflammatory response, granulation response, or fibrosis in the outflow system or in adjacent tissues. Rabbit eyes showed minimal mononuclear cell infiltration and minimal fibrotic responses at the site of the implants when compared with sham-treated control eyes. Conclusions: The Hydrus Microstent was associated with minimal inflammation in both NHP and rabbit eyes with extended follow- up. These preclinical studies demonstrate that the Hydrus Micro- stent appears to have excellent long-term biocompatibility. Key Words: glaucoma, IOP, human, Schlemm’s canal, MIGS, trabecular meshwork, drainage device (J Glaucoma 2013;00:000–000) BACKGROUND Surgical lowering of intraocular pressure (IOP) is a critical component in the treatment of glaucoma. 1–3 Tra- beculectomy and glaucoma drainage device implantation remain the most commonly performed surgical procedures for the treatment of open-angle glaucoma. These proce- dures bypass the physiological outflow system of the eye by creating an alternate nonphysiological outflow pathway. Numerous studies have demonstrated good efficacy for these surgical procedures. 1,4,5 However, a high rate of complications has prompted a continuous search for alternative surgeries to treat open-angle glaucoma. 6 There is increasing interest in minimally invasive glaucoma sur- geries. Recent publications 7,8 have reviewed the available microinvasive glaucoma surgical (MIGS) options. “MIGS” has been defined as a group of surgical procedures with an ab interno approach that reduce IOP without creating an alternate nonphysiological outflow pathway. Surgical procedures such as trabeculotomy or the Trabectome procedure attempt to open communication between Schlemm’s canal (SC) and the anterior chamber without device implantation. 9–16,12 The removal of the trabecular meshwork (TM), considered to be the site of greatest outflow resistance, provides aqueous humor a direct flow path into SC. The downstream resistance pro- vided by episcleral venous pressure is maintained following SC surgeries thus there is low risk of hypotony and related complications seen with more invasive glaucoma sur- geries. 17–22 However, wound healing can affect the patency of unsupported TM openings. More recently, several glaucoma implants have been designed to maintain a fluid pathway into SC without physical removal of the TM. 23–27 However, devices designed for implantation into SC have been limited by the lack of available materials with suitable properties and the inability to manufacture those materials to the proper dimensions. Current glaucoma drainage devices are constructed from materials with a long-standing history of use in tissue implantation. Materials for ophthalmic implantation have included stainless steel, titanium, silicone, and poly- propylene. 28–30 However, both common metal and polymer materials have limitations, each lacking optimal dimensional and material properties for SC placement and long-term function. Traditional materials such as silicone demonstrate flexibility, whereas materials such as stainless steel exhibit rigidity for support; however, materials rarely combine both properties. Because of the unique and tiny circum- ferential anatomy of SC within the anterior chamber wall, a material that is superelastic yet maintains its structure is desirable. Nitinol use in medical devices began in the 1970s. 31 Advantages of Nitinol, an alloy of 55% nickel and 45% titanium, include superelasticity, thermal shape memory behavior, high corrosive resistance, and biocompatibility. 32–37 These properties make Nitinol particularly suitable for use in applications requiring complex geometries, shape character- istics, and a circuitous delivery pathway; all conditions needed of a SC microstent. Because of its lack of cytotoxicity or mutagenic behavior, Nitinol recently has become a well- accepted alternative to traditional metallic and polymeric Received for publication January 3, 2013; accepted August 27, 2013. From the *Department of Eye and Vision Sciences, University of Liverpool, Liverpool, UK; wDepartment of Ophthalmology, McGill University, Montreal, QC; 8Department of Ophthalmology and Visual Sciences, University of Toronto, Mississauga, ON, Canada; zDepartment of Ophthalmology, University of Colorado School of Medicine, Aurora, CO; yDepartment of Ophthalmology, University of Washington, Seattle, WA; #Department of Oph- thalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE; and zIvantis Inc., Irvine, CA. Supported by Ivantis Inc., and an unrestricted grant from Research to Prevent Blindness. Disclosure: Andrew Schieber is employed by Ivantis. Malik Kahook consults for Glaukos. Murray Johnstone, Ike Ahmad and Ian Grierson consult for Ivantis. Reprints: Carol B. Toris, PhD, Department of Ophthalmology and Visual Sciences, 985840 University of Nebraska Medical Center, Omaha, NE 68198-5840 (e-mail: ctoris@unmc.edu). Copyright r 2013 by Lippincott Williams & Wilkins DOI: 10.1097/IJG.0000000000000012 ORIGINAL STUDY J Glaucoma  Volume 00, Number 00, ’’ 2013 www.glaucomajournal.com | 1