Study Design

The CyPass Micro-Stent is an investigational device that is currently undergoing United States Food and Drug Administration trials and has received the Conformité Européenne Mark, meaning it is available commercially in many European countries. DUETTE is an ongoing, multicenter, prospective, single-arm, interventional clinical trial evaluating the CyPass Micro-Stent implant. Patients with open-angle glaucoma (OAG) refractory to medical therapy and considered for conventional glaucoma surgery (trabeculectomy or shunt procedure) by the investigator were enrolled under a standardized treatment protocol ( ClinicalTrials.gov identifier NCT01166659 ). The DUETTE study protocol was approved by Freiburger Ethik-Komission International institutional review board (Freiburg, Germany), as well as by the ethics committee at each hospital, and adhered to the tenets of the Declaration of Helsinki. All subjects provided written informed consent before any study procedures were undertaken.

Study Subjects

All study subjects had a complete ophthalmic examination preoperatively, including medical history, slit-lamp examination, dilated funduscopic ophthalmoscopy, IOP measurement via Goldmann tonometry, and best-corrected distance visual acuity (BCDVA). Inclusion criteria were: presence of primary open-angle glaucoma with Shaffer Grade 3 or 4 as assessed by clinical gonioscopy, medicated IOP between 21 and 35 mm Hg, optic nerve vertical cup-to-disc ratio greater than 0.7, and visual field defect noted via the Humphrey Visual Field 24-2 Swedish Interactive Threshold Algorithm (SITA) Standard or equivalent, and failing to achieve or maintain target IOP control (per each investigator’s discretion) with use of 1–4 IOP-lowering medications, with consideration of conventional glaucoma surgery. Subjects could be either phakic or pseudophakic. Exclusion criteria included angle closure or Shaffer Grade 1 or 2 angles; diagnoses of traumatic, malignant, uveitic, or neovascular glaucoma; discernible congenital anomalies of the anterior chamber or iridocorneal angle; or known intolerance or hypersensitivity to topical anesthetics, miotics, mydriatics, or polyimide. Patients with previous incisional glaucoma surgery were also excluded, as well as patients with any clinically significant ocular pathology other than OAG.

Study Device

The CyPass Micro-Stent is a fenestrated micro-stent made of a biocompatible polyimide material ( Figure 1 ). It is 6.35 mm in length and 510 μm in external diameter. As the micro-stent is inserted, it assumes the curvature of the specialized applier guidewire to follow the scleral contour along the supraciliary space. When it is correctly inserted into the supraciliary space, the material stiffness, in conjunction with a series of retention rings at the proximal end, helps ensure the stability of the device in the angle and the supraciliary space. The micro-stent is designed to increase aqueous outflow via the uveoscleral pathway.

Illustration of the CyPass Micro-Stent threaded on the guidewire of the applier. The slight curve of the micro-stent on the guidewire facilitates insertion along the curve of the supraciliary space. Fenestrations in the micro-stent allow aqueous flow into the supraciliary and suprachoroidal spaces.

Surgical Implantation Technique

All glaucoma medications were stopped at the time of surgery except in circumstances where the principal investigator determined that it was in the subject’s best interest to continue some or all of these agents. Surgeons used their standard anesthesia regimen for anterior segment surgery. A shelved 1.5-mm corneal incision was performed at the limbus across from the target implantation site, acetylcholine was injected to achieve miosis, and then the anterior chamber was filled with a viscoelastic agent to maintain the chamber and expand the angle. The CyPass device was threaded onto the retractable guidewire of the applier, and implantation was carried out through the clear corneal incision.

The procedure was visualized using a goniolens (Ocular Instruments, Inc, Bellevue, Washington, USA), and insertion was initiated with the nonincisional tip of the guidewire, which allowed blunt dissection into the ciliary tissue to create a dissection plane between the ciliary body and the sclera. The micro-stent was inserted into the dissected area until it reached the supraciliary space and retention features were engaged. The guidewire was then retracted, leaving the micro-stent in place, and the applier withdrawn from the eye. Viscoelastic was evacuated using irrigation and aspiration. Each site used its standard course of postoperative antibiotics and steroids. Implant positioning was confirmed postoperatively with gonioscopy. In some cases, optical coherence tomography (Visante OCT; Carl Zeiss Meditec, Jena, Germany) or ultrasound biomicroscopy (Humphrey UBM 840, 50 MHz; Carl Zeiss Meditec) was used to assess the CyPass position.

Study Measures

Standard postoperative follow-up visits were at day 1, week 1, and months 3, 6, and 12. Reintroduction of IOP-lowering medications after surgery was left to the discretion of the investigator and dependent on the target IOP of each of the subjects. Ocular device–related adverse events as well as unanticipated adverse events were collected at each visit. Patient postoperative examinations included gonioscopic assessment of implant placement, slit-lamp examination, dilated fundus examination, and measurement of IOP and BCDVA. The primary outcome measure was paired IOP reduction at 12 months as compared to baseline. Paired IOP reduction is defined as the reduction in IOP for the study eye from baseline to the censored time point. Secondary endpoints included need for additional incisional glaucoma rescue surgery (trabeculectomy, tube shunt) and ocular hypotensive medication use at 12 months.

Statistical Methods

Postoperative IOP and medication use at 6 months and 12 months were compared to baseline in a paired, nonparametric analysis using the Wilcoxon signed rank test. Eyes that were reoperated were considered not evaluable and were therefore not included in the follow-up analysis, in order to reduce the confounding effect of additional glaucoma surgery.