Efficacy and adverse event profile of the iStent and iStent inject trabecular micro-bypass for open angle glaucoma: a meta-analysis

Methodological quality of the review: Low Confidence

Authors:  Popovic M, Campos-Möller X, Saheb H, Ahmed IIK

Region: Europe, North America, Japan

Sector: Glaucoma

Sub-sector: Treatment

Equity focus:  None specified

Review type: Other review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:

Given the irreversible retinal ganglion cell damage resulting from open-angle glaucoma (OAG), current treatment modalities are focused on preserving the structural integrity of the optic nerve and visual function. Reduction of intraocular pressure (IOP) leads to significant sparing of vision. IOP elevation is often a result of reduced aqueous humor flow through the trabecular meshwork. In early stages, ocular hypotensive medications and laser trabeculoplasty have been shown to attenuate glaucoma progression; however, there are well known issues with compliance, tolerability, persistence, and difficulty of proper instillation. In the situations where these treatments are insufficient in reducing IOP to target pressures according to disease severity, ab-externo filtering procedures are utilized to provide a more significant IOP reduction. Unfortunately, these techniques are higher risk options.

Recently, there has been increasing interest in the ability of microinvasive glaucoma surgery (MIGS) devices to provide a significant level of IOP reduction with less severe postoperative adverse events. One such device, the iStent, is the first ab-interno glaucoma implant that has been approved for the management of mild-to-moderate OAG. The following meta-analysis aims to investigate the efficacy and adverse event profile of iStent implantation for the management of OAG.

Objectives:

This meta-analysis explores the efficacy and adverse event profile of the iStent, an ab-interno implant for the treatment of open-angle glaucoma.

Main findings:

A total of 28 studies were included in this review. Within the cohort of 1,773 eyes for which there was relevant demographic information, the mean age was 71.4 ± 5.4 years (n = 1606; cohort range: 54.4–78.8 years), and 747 out of 1,662 eyes were male (44.9%). Most eyes came from Caucasian patients (870 out of 1,089 eyes, 79.9%). Generally, studies were moderate to high quality.

The meta-analysis has shown that there may be differences in treatment response for the iStent due to varying parameters, including the number of iStents and phaco-iStent compared to either iStent alone or phacoemulsification alone. In the authors’ analysis, two stents delivered a greater response in terms of IOP reduction relative to one, and iStent alone had a significantly greater IOP reduction compared to phaco-iStent. Combined phaco-iStent was statistically superior relative to phacoemulsification alone in the reduction of IOP and medication classes pre to post-operatively.

A limitation was that the lack of available studies prevented the authors from performing a robust meta-analysis for some endpoints, such as IOP reduction following three stents, (where there were only 63 included patients). Limited reporting of adverse event severity across studies prevented the authors from analyzing severity in the adverse event analysis. Studies were variable in how they handled medication washout before stent implantation, which made it impossible to analyze the effect of preoperative medications on baseline IOP. Given that data was extracted from study cohorts, conclusions should be limited to the level of the cohort.

Future research should determine whether similar conclusions are reached following meta analysis in a more controlled environment.

Methodology:

A systematic literature search was performed on Ovid MEDLINE (2006–Week 1 2018) and Ovid EMBASE (2006– 2018 Week 3). Further, Google, Google Scholar and the reference lists of past reviews were manually searched to elicit further relevant literature. Any original prospective or retrospective clinical study that provided relevant efficacy data (that is, IOP and number of medication classes) on the implantation of the iStent for at least five eyes was included. Only peer-reviewed journal articles were included. The most common adverse events were intraocular pressure elevation, stent blockage or obstruction, stent malposition and hyphema. Non-English studies, letters to the editor, correspondences, editorials, reviews, opinions, case reports, articles reporting on other surgical procedures and studies that contained repeat data or less than 4-week follow-up were excluded. Studies were screened first by consulting titles and abstracts and afterwards by examining full-text versions.

The authors used the Cochrane criteria to assess quality of randomized controlled trials, while the National Institute for Health and Care Excellence tool was used to evaluate case series. In both cases, the authors note excluding studies which were high risk of bias in at least half of the assessment categories.

Statistical analysis used weighted mean differences and corresponding 95% confidence intervals for primary and secondary outcomes.

Applicability/external validity:

The authors make clear that the meta-analysis had several limitations and as such its effects should be limited to the cohort described. Future research is needed to determine its general applicability.

Geographic focus

The authors did not report applicability of findings to low- and middle-income countries.

Summary of quality assessment:

The authors did not state whether the data was independently extracted by two independent reviewers, nor did they specify the methods they used to determine heterogeneity. In addition, they excluded studies on both language and publication status and declared a conflict of interest. For these reasons this review has been attributed Low Confidence.