Three-Year Efficacy and Safety Outcomes of the Second-Generation Trabecular Micro-Bypass Stents in Conjunction with Cataract Surgery in Ocular Hypertension and Open-Angle Glaucoma

Research Article

J Ophthalmol & Vis Sci. 2023; 8(4): 1087.

Three-Year Efficacy and Safety Outcomes of the Second-Generation Trabecular Micro-Bypass Stents in Conjunction with Cataract Surgery in Ocular Hypertension and Open-Angle Glaucoma

Jiaru Liu, MD¹; Soumaya Bouhout, MD¹; Erika Massicotte, MD, FRCSC¹; Anik Desgroseilliers², MD, FRCSC¹; Frederic Lord, MD, FRCSC¹; Harmanjit Singh, MD, FRCSC1,3

1Department of Ophthalmology, Centre Hospitalier de l’Université de Montréal, Canada

2Department of Ophthalmology, Université de Montréal, Canada

3Department of Ophthalmology, Queen’s University, Canada

*Corresponding author: Harmanjit Singh (HS) 27 Place d’Armes, Kingston, ON, Canada. Tel: (613) 507-4800 ; Fax: (613) 507-4801 Email: hmansingh25@gmail.com

Received: October 25, 2023 Accepted: November 30, 2023 Published: December 07, 2023

Abstract

Purpose: To evaluate the efficacy and safety of the iStent Inject in conjunction with phacoemulsification in patients with open-angle glaucoma.

Design: Prospective, non-randomized, single-center, consecutive case series

Participants: Patients with primary and secondary open angle glaucoma undergoing cataract surgery and iStent Inject

Main outcomes: The primary outcome of efficacy is postoperative reduction in mean Intraocular Pressure (IOP) and number of anti-glaucomatous drop classes. A primary endpoint is the achievement of =20% IOP reduction from baseline. Secondary outcome measures include visual acuity, visual field parameters, cup-to-disk ratio, and average retinal nerve fiber layer thickness.

Results: 150 eyes were included with a mean follow-up of 2.28 years (standard deviation 1.18). IOP significantly decreased at nearly all timepoints and remains significantly reduced from baseline at 36 months. IOP reduction is modest and ranges between 5.6 to 11.7 %, with IOP being stably maintained lower than baseline throughout the observation period. IOP reduction is greatest in the mild glaucoma group. The primary endpoint of an over 20% IOP reduction being achieved in overall 32% of eyes. The burden of glaucoma drops was significantly reduced by 13% at 12 months post-op (p<0.005). There was no statistically significant change in visual field parameters, although they improved after cataract surgery. The rate of additional glaucoma interventions needed were very low at <1%.

Conclusion: The combined cataract surgery and iStent Inject procedure is safe and effective at long-term with a low rate of serious complications. It offers good visual outcomes and reasonable glaucoma control long-term.

Keywords: Istent inject; Efficacy; Safety; MIGS; Cataract surgery

Introduction

Glaucoma, a progressive optic neuropathy, is the second cause of blindness in the world, affecting 76 million people in 2020 and predicted to affect 111.8 million by 2040 [1]. The disease is caused by the death of Retinal Ganglion Cells (RGCs) and the degeneration of their axons that convey visual stimulus to the brain, leading to irreversible loss of the visual field [2].

The only modifiable risk factor for the progression of glaucoma that we know to this day is the Intraocular Pressure (IOP) [3].

The Minimally Invasive Glaucoma Surgery (MIGS) using ab interno trabecular microbypass stents have been developed to optimize the conventional outflow of aqueous humour through the trabecular meshwork. The smaller, second generation iStent Inject (Glaukos) consists of two deployable, heparin-coated titanium stents that are released at two to three clock hours apart in the trabecular meshwork [4].

The increased circumferential spread from this new mechanism of action may allow for better IOP control than its first-generation counterpart at short term [5-7]. It was approved by Health Canada in 2015 as a standalone procedure or in combination with cataract surgery for patients diagnosed with primary open-angle glaucoma, pseudoexfoliative glaucoma or pigmentary glaucoma [5-11]. They are an advantageous option to treat glaucoma as they potentially lessen the burden of anti-glaucomatous medication instillation and avoid surgical complications from more invasive filtering or tube procedures [12,13].

Several studies have already proven the efficacy of the iStent Inject in lowering IOP and the number of drops in patients with mild to moderate glaucoma in a variety of glaucoma subtypes [10,11,14-17]. Although few studies have examined the long-term outcomes of the first generation iStent past 5 years [18-20], there is currently no long-term studies of the outcomes of second generation iStent implanted in patients with different subtypes of glaucoma. This present study offers a 3-year assessment of the efficacy and safety of the iStent Inject in conjunction with phacoemulsification in a large cohort of glaucoma patients.

Methods

Study Design

This study is a prospective, non-randomized, single-center consecutive case series. The objective is to assess the long-term outcomes of efficacy and safety in glaucoma patients receiving the iStent Inject with simultaneous phacoemulsification. This study obtained ethics approvals from Institutional Review Board of Centre Hospitalier de l’Université de Montréal (CHUM).

The main outcome measure is the efficacy of the iStent Inject, which will be based on the short-term and long-term IOP reduction and number of anti-glaucomatous drops used postoperatively. A primary endpoint we will monitor is the achievement of =20% IOP reduction from baseline at each follow-up. The secondary outcome is the safety of the iStent Inject, which comprises preoperative and postoperative visual acuity change, visual field parameters, average retinal nerve fiber layer thickness, and cup-to-disc ratio.

Inclusion and Exclusion Criteria

We aimed to recruit a total of a hundred patients, followed to at least 36 months post-operatively. Patients were recruited at the ophthalmology department of the Centre Hospitalier de l’Université de Montréal by three glaucoma specialists (H.S., A.D., F.L.).

We included all adult patients over 18 years of age with ocular hypertension and open-angle glaucoma (including primary, pseudoexfoliative or pigmentary) who underwent combined cataract surgery with iStent Inject from January 2016 to January 2019. Patients were either intolerant to topical medications, had inadequate IOP on topical medication only or post Selective Laser Trabeculoplasty (SLT) and had IOP less or equal to 25 mmHg.

We excluded patients with angle closure, as well as those diagnosed with other types of secondary glaucoma (uveitic, neovascular, pupillary block, congenital, post-traumatic angle-recession), those with uncontrolled IOP defined as over 25 mmHg and those with previous glaucoma surgeries within the past 3 years. Patients with corneal opacification with difficult view of the iridocorneal angle and acute or chronic intraocular inflammation were also excluded for this study.

Baseline and Follow-up Examinationss

Written informed consent for the combined procedure as well as for the study were obtained for all patients.

A complete ophthalmologic evaluation was done preoperatively and included Corrected Distance Visual Acuity (CDVA), complete slit-lamp biomicroscopy examination with gonioscopy, IOP measurement using the Goldmann applanation tonometer, central corneal thickness, and dilated fundus examination with assessment of the Cup-to-Disk Ratio (CDR) of the optic nerve are obtained. Visual field imaging is performed using the 24-2 Swedish interactive threshold algorithm (SITA 24-2. Humphrey, Carl Zeiss Meditec, Jena, Germany), and a bilateral optical coherence tomography with retinal nerve fiber layer thickness measurement (Cirrus HD-OCT, Carl Zeiss Meditec, Jena, Germany). There will be no washout period, as to avoid progression in patients with especially an advanced disease [9,21]. Glaucoma severity was graded based on the Canadian Ophthalmology Society clinical practice guidelines on the management of glaucoma in adults [22].

iStent Inject Device and Surgical Procedure

The surgery took place within ninety days following the screening appointment. The surgery was done under local anesthesia. A clear corneal incision was done temporally to easily access the nasal iridocorneal angle. The trabecular micro-bypass stents were implanted before phacoemulsification.

The injector G2-M-IS is preloaded with two iStent Inject® [4]. After proper patient positioning and microscope adjustment, the 23-gauge stainless steel tube connected to the injector was inserted through the temporal clear corneal incision. Under direct visualization with a direct gonioprism, the first stent is released through the nasal trabecular meshwork into the Schlemm’s canal when the surgeon pushes on the release button for the first time.

The surgeon repeats the same steps to deploy the second stent, which will be positioned two or three clock hours away from the first one [4]. The iStent Inject® GTS400 is a surgical-grade non-ferromagnetic gamma-sterilized titanium stent coated with heparin.

This one-piece stent measuring 0.3x0.4 mm features four small lateral lumens that will let the aqueous humor flows from the anterior chamber to the Schlemm’s canal to increase the natural aqueous outflow [4].

Post-Operative Follow-Up

The patients are given an antibiotic drop (moxifloxacin or equivalent) for seven days postoperatively, a corticosteroid drop and a non-steroidal anti-inflammatory drop for at least one month after the surgery (prednisolone acetate 1% or equivalent). There was no washout period to measure the IOP without anti-glaucomatous drops after the surgical procedure. The topical medication is maintained until the target IOP is achieved and then the drops are progressively reduced.

The patients are seen by their attending ophthalmologist one day, one week, one month, three months, six months, nine months and one year after the surgery. They are seen more often if any complication occurs. Thereafter, patients are seen again every 6 months to a year as per the usual glaucoma follow-up regimen. Every visit following the combined procedure, the patients underwent a complete ophthalmic evaluation including: CDVA, IOP measurement, gonioscopy, anterior segment and optic nerve assessment of the cup-to-disk ratio on non-dilated slit-lamp examination. At one-year postoperative, two additional tests are performed: standard automated perimetry using the 24-2 Swedish Interactive Threshold Algorithm (SITA 24-2) and Optical Coherence Tomography (OCT) with Retinal Nerve Fiber Layer (RNFL) thickness measurement. Imaging parameters are analyzed at 12 months, 18 months, 24 months, and 36 months post-op as the changes seen are expected to be more gradual. CDR is assessed at 6 months, 12 months, 18 months, 24 months, and 36 months post-op as the changes are also expected to be of slower onset.

Data Analysis

Statistical analysis was performed using the SPSS software (IBM Corp. Released 2020. IBM SPSS Statistics for macOS, Version 27.0. Armonk, NY: IBM Corp). Paired 2-tailed Student T-tests was used to compare changes in IOP, number of medications and CDVA between each time point. Because the paired T-tests were done in individual pairs, there was no need for a Bonferroni correction for the multiplicity of comparisons. Snellen visual acuities will be converted to logarithm of the minimum angle of resolution (logMAR) values for statistical analysis. A level of p=0.05 will be considered statistically significant.

Results

Baseline Characteristics

In total, 97 patients (150 eyes) were included in the study. Detailed demographic characteristics of the cohort are exhibited in table 1. Patients were on average 72 years old, (range 54-90). Most patients were diagnosed with Primary Open-Angle Glaucoma (POAG) with 68 patients (70%), followed by Pigment Dispersion Glaucoma (PDG) with 10 patients (10%) and Ocular Hypertension (OHT) with 10 patients (10.3%). Over half of the patients had mild disease severity, while 25% had moderate and 23% had advanced. On average, patients were on 2.6 classes of drops pre-operatively (standard deviation of 0.67 drops). The mean pre-op IOP was 17 mmHg (standard deviation of 3.8mmHg). Approximately 20% of patients received prior laser therapy (selective laser trabeculoplasty or argon laser trabeculoplasty). Two eyes (1.3%) had received micropulse cyclophotocoagulation prior to the intervention. Two eyes (1.3%) had prior vitrectomies prior to the iStent Inject implantation. One eye had received a Penetrating Radial Keratoplasty (PRK) before the combined cataract and five had prior refractive surgery.