Abstract
Background
To assess the safety and efficacy of iStent inject placement in individuals with glaucoma with open angles in real world clinical settings.
Methods
A review was conducted on the medical records of individuals who received iStent inject implants starting from March 2018. The analysis focused on reductions in intraocular pressure (IOP) and glaucoma medication usage. Safety assessments encompassed intraoperative and postoperative issues, additional surgeries, and improvements in best-corrected visual acuity (BCVA).
Results
Analysis of 55 eyes of 48 patients that underwent iStent implantation revealed a mean age of 77 years (range: 51–97). The initial average intraocular pressure (IOP) in these eyes was 20.2 ± 6.4 mm Hg. Following surgery, IOP decreased by ≥ 20% compared to preoperative levels in 21 eyes (43.8%) over the 12-month follow-up period. Notably, there was a significant reduction in medication usage by the 12-month mark ( P < 0.0042). Among the evaluated eyes, 9 exhibited a response to steroids, 3 had stents that were improperly positioned, 5 had stents that were over implanted, and 1 eye experienced an episode of iris prolapse.
Conclusions
The findings from the 12-month follow-up of iStent inject implants in standard clinical settings demonstrate a notable decrease in both intraocular pressure (IOP) and medication usage in eyes with concurrent open-angle glaucoma.
1
Introduction
Glaucoma, a progressive vision-threatening condition encompassing various optic neuropathies, poses a significant global health burden. Among its forms, primary open-angle glaucoma (POAG) stands out as the most prevalent, projected to impact over eighty million individuals by 2020 and remains a leading cause of blindness in developing nations. The irreversible optic nerve damage associated with glaucoma underscores the critical need for treatments aimed at preserving optic nerve structure and visual function. Central to this goal is the reduction of intraocular pressure (IOP), the primary modifiable risk factor linked to glaucoma progression and visual field loss. Notably, studies like the Early Manifest Glaucoma Trial (EMGT) have highlighted the strong correlation between decreased IOP and reduced risk of glaucoma progression.
While POAG, along with other forms of glaucoma like normal-tension glaucoma (NTG), pseudoexfoliation glaucoma (PXG), and ocular hypertension (OHT), often presents insidiously without symptoms, elevated IOP due to impaired aqueous humor outflow remains a key feature. Current treatment modalities primarily focus on IOP reduction through medications and laser procedures, yet challenges such as compliance issues and side effects persist. Factors contributing to glaucoma’s onset are multifaceted, including age, diabetes, myopia, family history, and ethnicity. Other factors like low cerebrospinal fluid pressure, poor ocular blood perfusion and genetic predisposition also play a significant role in the disease aetiology of variants like NTG. , Traditionally, initial management involves antiglaucoma medications; however, when target IOP levels are not met or disease progression continues despite maximal therapy, surgical intervention becomes necessary. Unfortunately, the more invasive surgical techniques like trabeculectomy and tube surgeries are associated with sight-threatening complications that may result in a blebitis, haemorrhage, hyphema, hypotony, endophthalmitis, inflammation, loss of vision or repeat surgery. Micro Invasive Glaucoma Surgery (MIGS) has emerged as a less invasive alternative to traditional surgeries like trabeculectomy, offering promising outcomes in lowering IOP. Trabecular bypass micro stents represent a key advancement in MIGS, providing a novel route for aqueous humor drainage and demonstrating significant reductions in both IOP and medication burden. , Randomized, controlled studies have shown significant reductions in both IOP and medication load post-implantation of one or more micro stents in conjunction with cataract surgery, beyond the reductions achieved with cataract surgery alone. , ,
This retrospective study focuses on evaluating the outcomes of implanting 2 s-generation trabecular micro-bypass stents in diverse glaucoma cases within real-world settings. By including patients often excluded from clinical trials due to specific criteria, such as those with pseudoexfoliation glaucoma or advanced disease, this research aims to provide valuable insights into the practical application of these innovative devices.
2
Methods
2.1
Ethical approval
All procedures were conducted following approval from the Institutional Review Board of Lancashire Teaching Hospital, Preston, in accordance with the principles outlined in the 1964 Helsinki declaration and its subsequent revisions or equivalent ethical guidelines. The study was registered with the research and development department of the institution. As the data collection was retrospective, it focused on patients already treated within the surgeon’s clinical practice, obviating the need for formal clinical trial registration. Patient details were meticulously recorded to prevent duplication, ensuring anonymity and confidentiality were rigorously upheld.
Each case record was assigned a random number for study purposes, with a separate secure, password-protected system storing the key linking these numbers to patient names. Subjects’ rights and welfare were safeguarded by presenting aggregated, anonymized data derived solely from medical chart reviews. Data extraction was directly from EVOLVE without the use of paper forms, with de-identified information securely stored in a password-protected database on a restricted network drive.
2.2
Methods
This study retrospectively examined the clinical records of patients who underwent iStent inject implantation consecutively between January 2017 and December 2018. Preoperative criteria included open-angle glaucoma with visible trabecular meshwork on gonioscopy, encompassing POAG, PXG, Pigmentary glaucoma (PG), NTG, mixed mechanism glaucoma, and OHT. Patients with glaucoma progression despite maximal antiglaucoma medications and poor ocular surface were included, irrespective of disease severity.
Exclusion criteria comprised eyes with active inflammation, corneal opacities hindering gonioscopy assessment, primary angle-closure glaucoma (PACG) and suspects, neovascular glaucoma, synechial angle closure, and elevated episcleral venous pressure. Pregnant women, individuals under 18 years old, and those with congenital glaucoma were not enrolled. Patients lost to follow-up or with significant ocular comorbidities were also excluded.
The iStent inject procedure is routinely performed at the ophthalmology department of Royal Preston Hospital. To ensure statistical significance, a large sample size was maintained, aiming for approximately 120 cases annually with a 10% attrition rate considered. The sample size was estimated at 200–220 cases to account for potential losses to follow-up post-surgery. However, the sample size in our study was smaller after taking inclusion and exclusion criteria into consideration. Patients with a followup of less than six months were also excluded.
Data collection utilized a structured proforma overseen by the principal investigator, which was piloted to identify and rectify any study-related errors. File numbers of patients undergoing the iStent inject procedure were retrieved from surgical records and electronically documented using EVOLVE software. Preoperative data encompassed demographics, best corrected visual acuity (BCVA), IOP, central corneal thickness (CCT), and preoperative medication details.
Postoperative information included IOP and medication burden at various intervals up to twelve months. Safety parameters recorded comprised postoperative BCVA, surgical complications, additional interventions. Patients had a minimum follow-up of six months postoperatively to enhance result validity. All adverse events and complications were meticulously documented, with ‘Serious’ adverse events meeting specific criteria such as life-threatening nature or requiring hospitalization.
A successful outcome post Istent was defined as ≥ 20% reduction in intraocular pressure (IOP) at 12 months without additional glaucoma surgery or medications, in line with the World Glaucoma Association’s (WGA) recommendations.
2.3
iStent inject design and surgical procedure
The iStent, developed by Glaukos Inc., is a first-generation trabecular bypass device that connects the anterior chamber to Schlemm’s canal. This device, approved by CE-mark and FDA, can be used independently or in conjunction with cataract surgery in Europe. It measures 1 mm × 0.3 mm, is constructed from heparin-coated, non-magnetic titanium, and comes pre-loaded in an inserter. The iStent inject, also known as the GTS-400 iStent inject, represents a second-generation model made of heparin-coated titanium with dimensions of 360 μm length and 230 μm diameter. Significantly smaller than its predecessor, the iStent inject is the smallest approved implantable medical device designed to reduce IOP effectively and safely.
Featuring a simplified learning curve due to its updated design compared to the original iStent, which had a snorkel structure, the G2-M-IS injector system allows for simultaneous implantation of two stents during a single procedure. Surgeons use this system to insert the stents into Schlemm’s canal via a stainless-steel insertion tube by pressing a button on the injector. Each iStent inject stent is positioned in the nasal trabecular meshwork and Schlemm’s canal at specific angles to facilitate multidirectional aqueous outflow through two fenestrations. The procedure can be performed through a temporal phacoemulsification incision or a temporal clear corneal incision as a standalone operation.
During surgery, patients are positioned supine with their head turned 35° counterclockwise for optimal visualization of the nasal angle using a direct gonioscope rotated 135° at the microscope eyepiece. Postoperatively, patients follow a standard regimen involving antibiotic (chloramphenicol 0.5%) eye drops for one week and anti-inflammatory (dexamethasone 1%) eye drops four times daily for four weeks with a gradual taper over one month. Glaucoma medications are typically continued preoperatively and may be adjusted postoperatively based on achieving target IOP levels at the surgeon’s discretion.
The positioning of the iStent inject is evaluated gonioscopically both during and after surgery at each clinical visit.
2.4
Statistics
In the study, descriptive statistics were employed to analyze the data. This involved determining means, frequencies, and proportions of the variables, with results presented through appropriate graphs, tables, and charts. The comparison of preoperative and postoperative IOP at different time points was conducted independently, along with assessing the effectiveness of the procedure by comparing preoperative IOP with IOP at 12 months. Additionally, preoperative and postoperative medication usage was compared. Categorical and numerical variables were analyzed using the Chi-square test and Student’s t -test, respectively. Statistical significance was defined as a p-value below 0.05. Data analysis was performed using SPSS statistical software (IBM Corp., Armonk, NY, USA).
3
Results
A total of 55 consecutive eyes of 48 patients who underwent iStent inject with a minimum of six months of follow-up data were included in the study. The mean age at the time of surgery was 77 years (SD = 10.4; range 51–97). The patient population predominantly consisted of individuals with POAG, PXG, and PD, all exhibiting an open-angle configuration at the stent implantation site. Among the eyes, 98.2% (n = 54) underwent simultaneous phacoemulsification and iStent inject implantation, while only one phakic eye received solely iStent inject implantation. Additionally, 7.3% (n = 4) of eyes were diagnosed with PD and 3.6% (n = 2) were diagnosed with PXG. Complete preoperative parameters and demographics are detailed in Table 1 .
| N (55) | % | ||
|---|---|---|---|
| Age at surgery (years) | Mean ± SD | 77.0 ± 10.4 | |
| Range | 51–97 | ||
| Gender | Male/Female | 30/25 | 54.5/45.5 |
| Treated Eye | OD/OS | 33/22 | 60.0/40 |
| Lens Status | Phakic/Pseudophakic | 1/54 | 1.8/98.2 |
| Angle Characteristics | Open | 55 | 100.0 |
| Diagnosis | Pigment Dispersion Syndrome | 4 | 7.3 |
| Pseudoexfoliation | 2 | 3.6 | |
| BCVA 20/20 or better | 14 | 25.5 | |
| BCVA 20/40 or better | 42 | 76.4 | |
The mean IOP decreased significantly from 20.2 ± 6.4 mmHg to 16.3 ± 4.77 mmHg in iStent eyes (p < 0.0001) at the 12-month postoperative mark ( Fig. 1 ). A mean percentage reduction of IOP by 14.1% was observed at the 12-month follow-up compared to baseline. There was no statistically significant difference noted in IOP between post-iStent inject measurements at 1 month and 12 months (p = 0.0995). Notably, twenty-one eyes (43.8%) achieved a reduction of 20% or more in IOP at the 12-month follow-up period. The mean changes in IOP over various intervals – 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months – are presented in Fig. 2 .
