Evaluating New Glaucoma Devices
Elevated IOP in clinical practice is usually seen in glaucoma or ocular hypertension. Glaucoma affects over 60 million people worldwide with approximately 8.4 million that are bilaterally blind from this chronic disease.1 Options for reducing IOP mainly rely on pharmacological agents, laser treatments, traditional interventions, and the introduction of microinvasive glaucoma surgery (MIGS). The last 20 years have seen significant changes in all of these strategies with the introduction of new glaucoma surgical devices. When evaluating any new glaucoma device, it is critical to examine three main aspects before incorporating it into a clinical and surgical care strategy. These are efficacy, safety, and cost-effectiveness.
Three Critical Items
Efficacy is essential for any new successful surgical device or technology. It is important to look at various IOP metrics such as absolute reduction, percentage reduction, and reduction to various goal ranges and then to indirectly look at the reduction of pharmacological agents used to lower IOP.
The safety profile of the device is also important. In the case of the iStent and iStent inject (Glaukos), we are discussing safety compared to phacoemulsification alone, as well as its safety as a glaucoma intervention when trying to delay the need for a trabeculectomy or tube stunt surgery. We are constantly on a quest for new devices because of the complications and safety challenges with traditional surgery both intraoperatively, as well as in the short- and long-term postoperative periods.
Although cost may not have a direct bearing to treatment, one should look at cost-efficiency from various perspectives: costs to the patient, costs to the health care system, and cost reductions to medications. One should also consider the management of perioperative and long-term sequelae of the surgical intervention. We are all familiar with the possible costs associated with burden of care and complications that might occur with traditional surgery and we need to learn more about those with MIGS.
iStent & iStent inject—The Best-Studied MIGS Device Today
The iStent and iStent inject remain the best-studied MIGS devices that we currently have available today. It was first to market, which gives us the longest experience of use and the most available data. It is also the most studied in terms of peer-reviewed literature among MIGS devices with more than 100 published data sets on the iStent and iStent inject. The challenge with glaucoma meta-analyses is that it is often hard to compare studies that are inherently heterogenous.
The data tell us that Glaukos trabecular microbypass technologies are an effective intervention that significantly lowers IOP more than phacoemulsification alone for an extended period of time (although many MIGS devices have 12-month data, iStent and iStent inject data often span longer periods of time, and 5-year data have been published in several reports).2 We also learned from the literature that Glaukos trabecular microbypass implants lead to a meaningful reduction of required medications needed by patients postoperatively for their long-term management of glaucoma.
In a meta-analysis study comparing the overall IOP-lowering effect of iStent as an isolated procedure, or in combination with cataract extraction, it was found that iStent effectively decreased IOP in both combination and isolated procedures.3 The study further demonstrated that multiple stent implantations showed incrementally greater results, which are now offered in the iStent inject system.
Another study examining the efficacy of the iStent trabecular microbypass stent (TBS) as standalone or in combination with phacoemulsification procedures showed similar results.4 The study demonstrated that patients with mild to moderate glaucoma controlled by one or two medications experienced IOP lowering superior to cataract surgery alone with reduction of medication burden. The safety profile of the TBS procedures—as in the iStent inject—was very favorable and well suited for an early MIGS interventions.
With MIGS, the one area in the literature that we look for additional evidence relates to the cost-effectiveness and quality-of-life measures of MIGS versus conventional glaucoma surgeries. In a Canadian-based study that examined the cost of treating patients with two iStent devices compared with long-term topical glaucoma medication therapy, the report indicated that the cost savings of the two iStent procedures was nearly half over a 6-year period compared with a three-drug therapy treatment plan.5 The study further implied that the iStent inject therapy would be cost-effective over time given the substantial reduction of medication burden associated with the iStent inject procedure.
A meta-analysis of another Canadian-based study examined the cost-utility of two TBS implants versus standard of care in patients with mild to moderate open-angle glaucoma.6 The study demonstrated an additional reduction of 1.13 medications per patient and a significant decrease in IOP in favor of TBS versus medication alone. This concluded that TBS implants such as the iStent inject lowered IOP, reduced the amount of medications, and led to fewer blind eyes, which decreased health care costs and improved quality-of-life factors.
Using Studies to Draw Comparative Claims
As program director of a residency training program I often discuss the methodology of examining evidence form peer-reviewed papers during journal clubs with residents. Glaucoma is known to be very tricky when it comes to research and comparing head-to-head results from clinical trials. The studies are typically heterogenous, which is simply the nature of glaucoma, making it hard to compare trials without dissecting the evidence and looking at several factors to determine whether you are looking at comparable measures.
Patient characteristics are often variable and reflect the severity of the disease. One has to examine baseline IOP, number of glaucoma medications required, and other measures of severity that will affect the outcomes of individual studies. The other aspect I look at carefully is the study protocol and how clearly has the protocol been described and applied during the study. It is always a red flag for me to see a predefined protocol that has been modified or to see endpoints redefined while the study is ongoing. When that is done it becomes very hard to draw any conclusions from such a clinical trial.
With the iStent inject and other MIGS clinical trials, we should not simply only look at efficacy in terms of IOP reduction but should also examine the burden of therapy. So, one has to qualify the IOP reduction in relation to a number of other parameters. It is also important to examine how decisions were made to advance medical therapy during the course of the study, to examine the protocol used, and to know if the investigators were masked to the device that was used. All these elements can introduce bias into the data and can affect the results of the study especially since we are looking at reduction of medication burden as an outcome. Additionally, another aspect to look at in clinical trials is how randomization was achieved to ensure the disease severity was randomly assigned to both arms of the study. All of these factors can affect outcomes and need to be considered when comparing data.
Company-Sponsored Comparative Studies: How Should Surgeons View These data sets?
Company-sponsored studies are often well-designed registration trials. Less commonly, some are aimed to compare one device to another, usually by selecting one or two metrics such as absolute or mean IOP reductions and numbers of medications. As stated earlier, when considering trial results, one should examine the design of the trial, baseline patient characteristics, randomization process, and the reported metrics of IOP reduction among others. A modification in study protocol during the course of a study is a red flag.
To elaborate more, when studies report on IOP reduction, it is important to detail whether this was washed out or medicated IOP. Also consider how many IOP measurements were performed (diurnal or single) and whether the investigators were masked. Does the study report absolute reduction or percentage reduction, which is reliant on how low or high the baseline pressure was?
One metric often reported with MIGS is the reduction of medication burden or whether patients remain “drop free” after the intervention. In many studies the decision to add medications can be under the discretion of the investigators who may or may not have similar thresholds to advance therapy and may also not be masked to the intervention. Based on all these varying factors, it may be difficult to compare clinical trials and come up with meaningful conclusions unless these factors are standardized.
The iStent and iStent inject remain two of the best-studied surgical MIGS devices currently available. From a safety and efficacy standpoint, there are abundant data for physicians and surgeons to review as they adopt a MIGS treatment strategy. For patients who are treated for mild to moderate glaucoma and undergoing phacoemulsification, the iStent inject is a safe and effective option to lower and maintain a safe IOP while reducing the need for topical medications.
1. Quigley HA. Glaucoma. Lancet. 2011;377:1367-1377.
2. Neuhann TH. Trabecular micro-bypass stent implantation during small-incision cataract surgery for open-angle glaucoma or ocular hypertension: long-term results. J Cataract Refract Surg. 2015;41(12):2664-2671.
3. Mahdavi Fard A, Patel SP, Pourafkari L, et al. Comparing iStent versus CyPass with or without phacoemulsification in patients with glaucoma: a meta-analysis. Ther Adv Chronic Dis. 2019; 10:2040622318820850.
4. Wellik SR, Dale EA. A review of the iStent trabecular micro-bypass stent: safety and efficacy. Clin Ophthalmol. 2015;9:677-684.
5. Iordanous Y, Kent JS, Hutnik CM, et al. Projected cost comparison of Trabectome, iStent, and endoscopic cyclophotocoagulation versus glaucoma medication in the Ontario Health Insurance Plan. J Glaucoma. 2014;23(2): e112-e118.
6. Patel V, Ahmed I, Podbielski D, et al. Cost-effectiveness of analysis of standalone trabecular micro-bypass stents in patients with mild-to-moderate open-angle glaucoma in Canada. J Med Econ. 2019;22(4):390-401.