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In this article, Dr Ianchulev discusses MIGS supraciliary microstenting, a compelling new approach for outflow enhancement that results in sustained reduction of IOP and anti-hypertensive topical medication use in OAG patients.
Take-home message: In this article, Dr Ianchulev discusses MIGS supraciliary microstenting, a compelling new approach for outflow enhancement that results in sustained reduction of IOP and anti-hypertensive topical medication use in OAG patients.
By Dr Tsontcho [Sean] Ianchulev, MD MPH
Conventional glaucoma surgeries (e.g., trabeculectomy and shunts) have provided us with important treatment modalities for advanced glaucoma for many decades, but safety profiles and postoperative complications limit these approaches to the end-stage of the glaucoma disease spectrum. Even then, the trade-offs are significant.1
On the other hand, medical glaucoma treatment is life-long, expensive, and limited by patient compliance. More than 50% of glaucoma patients fail primary topical therapy and require two or more medications, which compounds adverse effects (AEs) and further diminishes compliance. New micro-invasive glaucoma surgical (MIGS) interventions aim to fill the gap and provide effective long-term IOP control while reducing medication use, without the safety concerns of filtering glaucoma surgery.2
One of the emerging MIGS modalities is supraciliary stenting, which creates a permanent conduit at the sclera - ciliary body interface to direct aqueous outflow to the suprachoroidal space. This separate drainage collateral augments the uveoscleral outflow pathway and makes use of the high resorptive capacity of the choroid and its negative colloidal pressure to provide a strong driving force for aqueous drainage.3 And while earlier surgical approaches to increase supraciliary outflow through an artificial fistula caused bleeding, inflammation, and scarring that limited success,4,5 the newer, ab-interno micro-invasive method with the CyPass microstent is able to achieve supraciliary access with minimal tissue trauma and in bleb-less, conjunctiva-sparing approach.6
The CyPass® Micro-Stent (Transcend Medical, Inc., Menlo Park, CA) is a 6-mm-long, biocompatible, polymeric, supraciliary implant that creates a new permanent aqueous outflow channel from the anterior chamber (Figure 1A). The device is a fenestrated tube (300 µm-diameter lumen) that is inserted into the supraciliary space through a small corneal incision such as that used for cataract surgery.
The CyPass is implanted under topical anesthesia similar to that used for phacoemulsion cataract surgery (phaco). A 1.5-mm clear-corneal incision is performed, acetylcholine is injected to achieve miosis, and the anterior chamber is filled with viscoelastic agent to maintain chamber integrity and expand the angle. The CyPass device is threaded onto the retractable guidewire of its applier, inserted through the corneal incision, and implanted into the supraciliary region via blunt dissection. Gonioscopy is used to guide implantation and to postoperatively confirm correct microstent positioning. Viscoelastic is then evacuated and a self-sealing incision is confirmed prior to completion of surgery.
In earlier European studies, microstent implantation in combination with phaco normalized ocular hypertension in glaucoma patients by sustainably reducing IOP by 30-35% through at least postoperative 12 months.6-8 By optical coherence tomography (OCT), an aqueous-filled internal filtration reservoir surrounds the microstent (Figure 1B-C), and early studies by Ahmet et al indicate that cleft size apprears to correlate with effective drainage.9
The Duette Trial
In a prospective, multicentre, single-arm clinical trial (DUETTE study, ClinicalTrials.gov Identifier NCT01166659),7 we evaluated the safety and effectiveness of CyPass Micro-Stent implantation for reducing IOP and medication use in POAG patients who had failed ≥1 class of topical medical therapy. Of 65 eyes all achieved successful implantation. All subjects met inclusion criteria and had the diagnosis of POAG which had failed topical medication therapy with at least one IOP lowering medication and the entry medicated IOP was over 21 mmHg. At baseline, mean medicated IOP was 24.5 +/-2.8 mmHg and mean number of topical medications was 2.2 +/- 1.1. Consistent with the MIGS profile of the CyPass device, there were no vision-threatening serious ocular adverse events, and the most frequent ones were transient intraoperative blood reflux (6%), transient IOP elevation (11%), cataract progression (7%), PAS (3%). More than 80% of subjects were controlled with the CyPass procedure and avoided filtration surgery, which was indicated for nearly all subjects at baseline. At the 12-month visit, 47 eyes were available for efficacy evaluation. In a paired analysis, IOP was reduced by a mean of 32% as compared with baseline to a mean value of 16.7 ± 5.5 mmHg (p<0.0001) and the mean number of IOP-lowering medications was 1.5 ± 1.3 (p=0.008), with an average reduction of 0.5 medications per subject.
The Warsaw Experience
A smaller single-center study in Poland followed 23 POAG patients that received a CyPass device during concurrent phaco.10 Baseline medicated IOP 16.9±5.0 mmHg was reduced at 1 and 2 years to 14.2±3.0 mmHg (n=19) and 15.1±1.8 mmHg (n=18), respectively. The number of glaucoma medications was reduced from 2.3±0.9 at baseline to 0.3±0.7 medicines at 2 years.
The Cham Experience
A similar trial in Germany tracked 24 POAG patients with uncontrolled IOP that underwent microstent implantation during phaco.11 Baseline IOP of 22.3±6.6 mmHg was reduced and maintained at 15.0±3.4 mmHg at 12 months (n=17), representing a paired 21% reduction. Subjects that had been taking a mean 1.8±1.2 IOP-lowering medications at baseline had this number reduced by more than half, to 0.7±1.0 at 12 months.
The CyCLE Trial
The aforementioned study sites are participants in a much larger, ongoing, multicentre study, the CyPass Clinical Experience Study (CyCLE; ClinicalTrials.gov Identifier NCT01097174), that has enrolled and treated 555 POAG patients with microstent implantation. One included sub-study is detailed as follows. A prospective European trial6 evaluated microstenting in combination with phaco for 2 years in a POAG patient pool that was divided into medicated subjects with either uncontrolled IOP (≥21 mmHg, Cohort 1, n=51) or controlled IOP (<21 mmHg, Cohort 2, n=85). No sight-threatening AEs occurred. The most common AEs were transient hypotony (15%) and microstent obstruction (9â%), typically due to iris tissue overgrowth. Fifteen subjects (11â%) required secondary incisional glaucoma surgery. Of 82 subjects remaining in the study at 24 months, mean IOP in Cohort 1 (n=23) was15.8 ± 3.8 mmHg, reflecting a 37â±19â% decrease from baseline (P <0.0001). Although Cohort 2 (n=59) IOP was significantly decreased at 6 and 12 months vs. baseline, the mean 24-month IOP, 16.1±3.2 mmHg, was unchanged from baseline. At 24 months, the mean ± SD number of medications was 1.0 ± 1.1 in Cohort 1 and 1.1 ± 1.1 in Cohort 2. Mean decrease from baseline medication use was statistically significant at months 6 (P <0.001), 12 (P <0.001), and 24 (P = 0.0265) in Cohort 1, and at months 6, 12, and 24 (all P <0.0001) in Cohort 2.
There are a wave of robust RCTs on the horizon that together will provide level-1 clinical evidence in the field of glaucoma.
The COMPASS Study
The COMPASS study (ClinicalTrials.gov Identifier: NCT02448875) is one of the largest MIGS trials to date - sample size 505 subjects randomized to either the cataract surgery (control group) vs cataract surgery with concurrent CyPass Micro-Stent implantation (active treatment). It is the first FDA study with 2-year efficacy and safety primary endpoints, and the first MIGS trial to control for medication confounding by using 1- and 2-year terminal washout as well as diurnal IOP measurements. The COMPASS study was just completed and the company announced that the trial met all primary and secondary endpoints at both 12 and 24 months. Data were recently submitted to the FDA and are pending publication.
In a new randomized, international trial (ClinicalTrials.gov Identifier: NCT02448875), we are currently evaluating whether a new MIGS approach to increase the size of the supraciliary peri-stent aqueous reservoir additionally reduces IOP and glaucoma medication use in microstented POAG eyes. To date, 63 eyes of 63 POAG patients (mean age 68 years, range 45â86) were randomized to receive either the supraciliary microstent alone, or microstenting with supplemental viscoexpansion using 30 or 60 µl of viscoelastic agent (Healon® 5; Abbott Medical Optics, Inc., Abbott Park, IL).
Adaptive viscoelastic spacer is injected through the device applier during microstent implantation, to enlarge the supraciliary space and increase outflow capacity. The 60 µl injected amount of viscoelastic represents a volume that is 40-fold greater than that of the microstent alone.
Although size attenuation occurred over time, viscoexpansion significantly and dose-dependently enlarged the cross-sectional area of the peri-stent aqueous reservoir (Table 1). At 6 months, the mean reservoir area was 4.7-fold larger in the Visco-60 group vs the Stent-only group. Preliminary data analysis indicates that viscoelastic expansion maintains persistent reservoir enlargement beyond 12 months and is associated with reduced IOP and glaucoma medication use.
Table 1. Viscoexpansion enlarges the peri-stent, supraciliary, aqueous drainage reservoir
Data are mean (SD); n=21 subjects/group. Cross-sectional area measured immediately posterior to the microstent by quantitative analysis of OCT images. Two-tailed Student’s t-test.
There were no serious vision-threatening AEs and we are monitoring all subjects through 12 months of follow-up. The safety profile of the CyPass Vx procedure appears similar to Cypass alone implantation and are consistent with what we see from MIGS interventions.
Growing experience and evidence with ab-interno stenting of the supraciliary space using the CyPass Micro-Stent, alone or in combination with phacoemulsification cataract surgery or viscoexpansion, demonstrates a MIGS-like safety profile with sustained treatment effect through 24 months of follow-up. With the results of the COMPASS study demonstrating positive 2-year efficacy in an FDA randomized clinical investigation, this will eliminate some of the concerns with trabecular by-pass stenting where the effect was not sustained at 2 years with statistical significance in the FDA trial. And with the advent of adapting visco-expansion to augment microstent-mediated supraciliary drainage, we may soon have a minimally invasive solution for patient care over the broad spectrum of glaucoma severity.
Dr Tsontcho [Sean] Ianchulev, MD MPH
Dr Tsontcho Ianchulev is a Clinical Associate Professor at the Department of Ophthalmology, University of California at San Francisco, and Chief Medical Officer of Transcend Medical, Inc., Menlo Park, California, USA.
Disclosure: Dr. Ianchulev has following disclosures: Financial interest and patent holder in Transcend Medical; Inventor of the technology for Intraoperative Aberrometry and financial interest / patent holder in Wavetec, Inc/Alcon; Venture Partner in PME & Tullis Health Ventures with interests in portfolio companies; previously Head of Clinical Development, Genentech;