In this episode of Interventional Mindset, Preeya K. Gupta, MD, sits down with I. Paul Singh, MD, to discuss the benefits of treating refractory glaucoma patients with the iStent infinite.
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What is refractory glaucoma?
With the broader adoption of microinvasive glaucoma surgery (MIGS), many glaucoma specialists are gradually redefining refractory glaucoma. Refractory glaucoma traditionally was thought to be classified as advanced nerve fiber layer loss (i.e., an optic nerve head with a 0.9 cup/disc ratio) along with significantly reduced visual field (both hemifields and/or loss within 5° of fixation) since glaucoma disease severity is often graded based on visual field loss.
However, the modern definition has shifted to include any patient who is truly not at target intraocular pressure (IOP) despite medical therapy or perhaps even because they cannot tolerate medical therapy. These patients may have mild visual field loss, or they may be advanced, but they are refractory in their response to conventional treatment.
Managing refractory glaucoma patients
As such, in Dr. Singh’s professional medical opinion, refractory glaucoma refers to patients who are recalcitrant, meaning they are unable to stay on their current regimen long-term to manage their symptoms sufficiently.
Consequently, it is critical for glaucoma specialists to keep target IOP in mind when evaluating patients. Mild to moderate glaucoma patients tend to have higher target pressures, allowing surgeons to utilize conventional outflow MIGS procedures to bring down their IOP in this refractory patient population.
What’s shifted in the past 5 to 10 years is that there are now improved surgical options available to manage glaucoma patients outside of eye drops, especially considering how patient non-compliance is a consistent issue, added Dr. Gupta.
How does ocular surface disease factor into refractory glaucoma?
Dr. Singh mentioned a study from Christophe Baudouin that showed a 30% reduction in patient compliance if there is concomitant ocular surface disease (OSD).1 Patients often get dry eye symptoms from these medications due to benzalkonium chloride (BAK) exposure in addition to tear film disruption from the medicated compounds themselves.
This can lead to issues with compliance and secondary loss of good IOP control. Additionally, over time, the more IOP fluctuation that patients experience, the higher the chances of disease progression, he added.
Similar results were seen in the LiGHT trial, which compared the efficacy of selective laser trabeculoplasty (SLT) versus IOP-lowering eye drops for patients with early glaucoma or ocular hypertension (OHT).2 Over time, patients in the SLT arm tended to have less progression than patients in the eye drop cohort despite having similar IOP levels between groups.2
Dr. Singh remarked that his treatment goal is to get patients on as few topical medications as possible while simultaneously reducing non-compliance, IOP, and OSD symptoms through interventional therapies. He aims to address compliance before the disease progresses to a moderate or severe stage, wherein aggressive treatment is required.
Additionally, multiple studies have shown that inflammation on the ocular surface can cause trabeculitis, which is potentially why the outflow worsens in some patients, as there is an unmanaged inflammatory cascade at the level of the trabecular meshwork (TM). When discussing how to define a successful glaucoma treatment, Dr. Singh maintained the value of partly defining the success based on the reduction in medication burden for patients.
Redefining "aggressive treatment" in glaucoma
Dr. Gupta added that generally, clinicians tend to consider glaucoma surgery (such as MIGS and laser procedures) as aggressive treatment; however, this is not necessarily in line with current consensus on these surgical techniques. She now considers MIGS and laser procedures as being less aggressive due to their minimally invasive natures and excellent patient tolerance.
While surgery still requires extra precautions and careful consideration, she highlighted that the gap is quickly closing in the risk-benefit analysis between glaucoma surgery and chronic medication. Dr. Gupta now considers them to be in similar risk categories since it is not as favorable to keep a patient on eye drops long-term.
Treating moderate glaucoma patients with conventional outflow MIGS procedures
Dr. Singh was involved in a clinical trial for the iStent infinite, which received approval from the Food and Drug Administration (FDA) in late 2022 as a combined treatment with cataract surgery and standalone glaucoma procedure for refractory glaucoma patients.
A brief overview of the iStent infinite
The iStent infinite was designed to provide 24/7 continuous control over IOP to prevent issues with patient non-compliance and adherence. The device features three multidirectional stents designed to restore natural outflow to up to 240° of collector channels. Of note, these stents occupy less than 3% of the TM, leaving the remaining 97% untouched.
Some key features of the iStent infinite that distinguish it from the iStent inject W include the loader, which has a self-retracting sleeve, and the method of implantation. The sleeve also acts as a tamponade for the viscoelastic to prevent flattening of the chamber, which aids in visualization during the implantation.
While the iStent inject W implants the stent with a “jack hammer-like” technique that occasionally causes the stent to come back out of the canal and require rethreading, the iStent infinite is implanted by maintaining constant contact with the TM, preventing any potential problems with rebound.
Pivotal trial for the iStent infinite
In the prospective, multicenter, 12-month pivotal trial for the iStent infinite, 72 patients with primary open-angle glaucoma (POAG) who had failed prior surgical and medical interventions underwent standalone iStent infinite implantation.3
In comparison to previous trabecular bypass MIGS pivotal trials, this patient cohort had a significantly higher pre-operative treatment burden with more severe POAG. For the patients enrolled in the study, the mean medication burden was 3.0, and the mean baseline IOP was 23.5mmHg.3
Results from the iStent infinite clinical trial
In a subgroup analysis of 11 patients who were previously on a maximum tolerated medical therapy (MTMT), 81.8% of patients had a >30% reduction in mean diurnal IOP, and 27.3% had a >40% IOP reduction.3 Investigators found that patients in this group with no previously failed glaucoma surgeries and MTMT experienced the most significant mean IOP reduction out of all of the cohorts.
Additionally, the trial demonstrated that 76.1% of patients with previously failed invasive glaucoma surgeries (i.e., trabeculectomy, tubes, etc.) and MTMT had a 20% or greater reduction in mean diurnal IOP from baseline on same or lower hypotensive medication burden.3 Further, 93.0% of patients had a reduced or maintained drop burden compared to baseline, and 53.0% of study participants had a 30% or greater reduction in mean diurnal IOP on the same or fewer medications from baseline.
Also, 74.2% of study participants achieved <18mmHg IOP on the same or fewer medications.3 As mentioned above, in the MTMT subgroup, 100% of subjects had an average IOP of <21mmHg, 81.8% had a mean IOP of <18mmHg, and 63.6% had a mean IOP of <15mmHg while on the same number or less medications.3
Dr. Singh emphasized that the results of this trial show that the earlier that surgeons can intervene with conventional outflow MIGS procedures, the better chance they have to bring the IOP levels down to the low teens and reduce the chance of or delay, the need for future glaucoma surgeries. Lastly, the iStent infinite demonstrated a favorable safety profile with no explants, infections, or device-related interventions or hypotony.
Dr. Singh’s surgical pearl for preventing hyphemas
A concern surgeons may have with implanting stents is the risk of hyphema following the procedure; however, Dr. Singh offered a surgical pearl to prevent this. He recommended not letting the anterior chamber collapse after implanting the iStent infinite. Instead, it’s better to slowly decompress the chamber over the span of 30 seconds to give time for the anterior chamber and episcleral venous system to equilibrate.
Conclusion
The data shows that conventional outflow MIGS procedures can greatly benefit refractory glaucoma patients before they progress to moderate or severe disease.
Adopting these techniques allows surgeons to reduce the medication burden on patients, improve compliance, and reduce IOP levels with one procedure.
