What was the aim of this review?
The aim of this Cochrane Review was to find out whether the implantation of one or more iStent or iStent inject devices ('iStents'), compared with conventional medical, laser, or surgical treatments, can keep people who have primary open-angle glaucoma from needing to use glaucoma drops (i.e. keep them 'drop-free'). The glaucoma drops are used to control the fluid pressure within their eyes (called the intraocular pressure (IOP)). We also looked at average change from baseline in number of glaucoma drops needed to control IOP, average change from baseline (i.e. before treatment) in IOP, and health-related quality of life as defined by study investigators. We examined all outcomes at short-term (less than six months), medium-term (six to ≤ 18 months), long-term (> 18 months and ≤ 36 months) and greater than 36-month time points. We collected and analyzed all relevant randomized controlled trials (RCTs; clinical studies where people are randomly put into one of two or more treatment groups) to answer this question and found seven RCTs evaluating iStents.
There was very low-quality evidence that treatment with iStents may have resulted in higher proportions of people who were drop-free at medium-term time points or who had better control of their IOP. None of the seven RCTs examined how the iStent affected quality of life and reporting on complications was highly variable. At present, clinical practice decisions should be based on provider judgment and patient preferences, given inconsistency in results and risk of bias in relevant studies published to date.
What did we study in this review?
Glaucoma is a group of eye diseases that cause irreversible damage to the optic nerve in the eye. If untreated, glaucoma can lead to blindness. Elevated IOP is the only known modifiable risk factor for open-angle glaucoma, which is the most common form of glaucoma. Conventional first-choice treatments for open-angle glaucoma include medical (e.g. glaucoma drops) or laser interventions. Surgery, which has a higher risk profile, is offered when glaucoma progresses despite treatment with medication or laser.
Minimally invasive glaucoma surgical procedures involve implantation of devices such as the iStent. They have been proposed as a safer alternative to standard glaucoma surgeries in people with mild-to-moderate forms of open-angle glaucoma. The iStent creates a 'bypass' between the front chambers of the eye and its natural drainage pathway. This bypass increases the flow of fluids out of the eye, which may decrease IOP and the need to use glaucoma drops to control IOP.
What were the main results of this review?
We identified four RCTs that randomized participants to treatment with iStents in combination with cataract surgery (called phacoemulsification) or with phacoemulsification alone. Additionally, we identified two RCTs that randomized participants to treatment with iStents or to medical interventions. We also identified one RCT that randomized participants to treatment with one iStent, with two iStents, or with three iStents. The manufacturer of the iStent provided funding and sponsorship for all the RCTs in this review.
Based on low-quality evidence, we found that participants who received iStent in combination with cataract surgery were more likely to be drop-free and may have experienced a modest reduction in number of glaucoma drops used per day to control IOP in the medium term, compared with participants who underwent cataract surgery alone; however, there was no difference in average change from baseline in IOP between the two groups.
Due to substantial heterogeneity, we did not conduct an analysis of the two studies comparing treatment with iStent to medical therapy. Investigators of those two studies reported that no participants in the medical therapy group were drop-free at 12 months, compared to over 90% in the iStent treatment groups. Data suggested that treatment of people with two or with three iStents may have been more effective than treatment with one iStent in terms of IOP control.
None of the seven studies included in this review provided information on quality of life, and differences in complications or side effects between treatment groups were uncertain, given few reported events and varied effectiveness.
How up to date is the review?
We searched for studies published up to 17 August 2018.
There is very low-quality evidence that treatment with iStent may result in higher proportions of participants who are drop-free or achieving better IOP control, in the short, medium, or long-term. Results from the 13 studies with results not yet available may clarify the benefits of treatment of people with iStent. Additionally, future MIGS studies should consider measuring quality of life and outcomes that reflect people's ability to perform vision-dependent activities.
Glaucoma is a leading cause of irreversible blindness worldwide. In early stages, glaucoma results in progressive loss of peripheral (side) vision; in later stages, it results in loss of central vision leading to blindness. Elevated intraocular pressure (IOP) is the only known modifiable risk factor for glaucoma. Minimally invasive glaucoma surgical (MIGS) techniques, such as ab interno trabecular bypass surgery with iStent (Glaukos Corporation, Laguna Hills, CA, USA), have been introduced as a new treatment modality for glaucoma. However, the effectiveness of MIGS on keeping people 'drop-free' (i.e. not having to use eye drops to control IOP) and other outcomes is uncertain.
To assess the effectiveness and safety of ab interno trabecular bypass surgery with iStent (or iStent inject) for open-angle glaucoma in comparison to conventional medical, laser, or surgical treatment.
Cochrane Eyes and Vision's Information Specialist searched the following databases on 17 August 2018: the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register; 2018, Issue 7), MEDLINE Ovid, Embase Ovid, the ISRCTN registry, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We applied no date or language restrictions. We searched the reference lists of reports from included studies.
We included randomized controlled trials (RCTs) that had compared iStent or iStent inject to medical therapy, laser treatment, conventional glaucoma surgery (trabeculectomy), or other MIGS procedures. We included RCTs that had compared iStent or iStent inject in combination with phacoemulsification to phacoemulsification alone.
We used standard methodological procedures expected by Cochrane. Two review authors independently screened search results, assessed risk of bias, and extracted data from reports of included RCTs using an electronic data collection form.
We included seven RCTs (765 eyes of 764 participants; range per study 33 to 239 participants) that evaluated iStent in people with open-angle glaucoma. We also identified 13 studies that are ongoing or awaiting publications of results. Most participants in the included studies were women (417/764 (55%) participants) and older age (age range: 49 to 89 years). We assessed most trials at unclear or high risk of bias: four trials did not clearly report the method of generating the random sequence or concealing allocation; five were unmasked, open-label studies, which we assessed at high risk of bias for performance and detection bias. All seven trials were funded by the Glaukos Corporation. We graded the certainty of evidence as very low.
Four RCTs compared iStent in combination with phacoemulsification to phacoemulsification alone. The summary estimate which we derived from two of the four RCTs suggested that participants in the iStent in combination with phacoemulsification group were 1.38 times more likely to be drop-free between six and 18 months than those in the phacoemulsification alone group (risk ratio (RR) 1.38, 95% confidence interval (CI) 1.18 to 1.63, I2 = 67%). Data from two RCTs also suggested that iStent in combination with phacoemulsification compared to phacoemulsification alone may have offered a small reduction in number of IOP-lowering drops (mean difference (MD) –0.42 drops, 95% CI –0.60 to –0.23). It is uncertain whether there was any difference in terms of mean reduction in IOP from baseline (no meta-analysis).
Two RCTs compared treatment with iStent to medical therapy; one of the two trials used the iStent inject. We determined the two trials to be clinically and methodologically heterogeneous and did not conduct a meta-analysis; however, the investigators of both trials reported that over 90% of participants in the treatment groups were drop-free compared to no participants in the medical therapy groups at six to 18 months.
One RCT compared treatment with one versus two versus three iStents. There was no difference in terms of participants who were drop-free at 36 months or less; however, at longer follow-up (i.e. at 42 months) participants in the one iStent treatment were less likely to be drop-free than those in the two iStent (RR 0.51, 95% CI 0.34 to 0.75) or three iStent (RR 0.49, 95% CI 0.34 to 0.73) treatment groups. The study did not report the mean change in number of IOP-lowering drops.
The type and timing of complications reported varied by RCTs. Similar proportions of participants who underwent treatment with iStent in combination with phacoemulsification and who underwent phacoemulsification alone needed secondary glaucoma surgery. None of RCTs reported findings related to quality of life.