New Paradigm, New Product

Continuing our series on interventional glaucoma, the panel of experts turn their attention to the new possibilities offered by the interventional approach. Standard glaucoma management relies on topical medication to control IOP – until visual field losses demand riskier approaches. But eye-drops have some depressingly familiar disadvantages – including ocular surface damage and reduced quality of life – resulting in irregular compliance and therefore suboptimal efficacy. Even with efficacious drops, as Davinder Grover points out, long term usage of drops could also damage the eye and its outflow pathway. Indeed, even perfectly compliant patients may not benefit from eye-drops as much as first thought. As Ike Ahmed says, “Measuring IOP over 24 hours reveals significant fluctuation – a risk factor for progression.” He asserts that relying on medication in early disease carries risk in itself: “The longer we delay intervention, the more the damage to the outflow system – irreversible pathology which itself interferes with therapy.”

Paul Singh agrees, saying, “Delayed intervention just gives you more aggressive disease and more challenging IOP targets.” The answer, surely, as Deborah Ristvedt suggests, is early procedural intervention to optimize natural outflow pathways before they become irreparable.

But an earlier procedural approach demands interventions that are both safe and effective without the unwanted side effects of traditional, invasive surgery. Does the iStent infinite meet these criteria? Data from the infinite pivotal clinical trial (1) are very promising. In brief, the trial reported over 20 percent IOP reduction in over 70 percent of patients; a remarkable efficacy rate in this complex population, says Tom Samuelson. Mark Gallardo notes that even subjects with refractive glaucoma (maximum tolerated medical therapy and/or tube or trabeculectomy history) achieved reduced medication and lower IOP. Nate Radcliffe points out that many iStent infinite recipients dispensed with eye-drops altogether, and suggests this may be because device implantation does not give rise to the IOP fluctuations associated with intermittent medication.

John Berdahl sums up the infinite trial like this: “I was surprised – not that the results were good, but by just how good they were!” He also notes that the study refutes the idea that the natural outflow pathway cannot be resurrected after traditional, invasive surgeries were performed in the past. “The trial challenges old dogma,” he says, “and gives patients a better option.”

Singh emphasizes the flexibility of the iStent approach, in that responder rates and IOP reduction can be improved by implanting additional iStents – up to three per eye.

Regarding safety, Ahmed points out that the iStent has been in use for a decade. “With over one million implantations, I think we’d know if there were any concerns – it’s probably the safest glaucoma procedure that surgeons undertake,” he says. “Even in the difficult cohort recruited for the infinite trial, there were no implant failures or serious adverse events.”

Gallardo concurs: “I’m very comfortable implanting iStent Infinite in phakic or pseudophakic patients, even when they are on just one medication. I also recommend it to patients who have had or are undergoing filtration surgery.” Radcliffe points out that the large, statistically robust trial gives doctors and patients a high level of confidence in the product. Samuelson agrees, and points out that canal-based surgery is never associated with hypotony and is therefore safer than many other glaucoma procedures. Similarly, Berdahl notes that early intervention with iStent should reduce the need for secondary surgical interventions, and thus avoid their associated risks. Radcliffe reminds us that discussions of iStent safety should take account of the fact that glaucoma itself is not safe, in that it jeopardizes patient vision, and that medication also has risks. “Poor compliance – which occurs weekly with most patients – can trigger extraordinarily high IOP within hours,” he says.

Bedrood notes that the iStent infinite safety profile makes it a good option for a very broad range of patients, not limited to mild-to-moderate cases.

In conclusion, says Ahmed, early glaucoma presents a one-time opportunity for changing the course of disease. “If you miss that chance, the patient’s needs and risk–benefit profile change adversely,” he says. “Ideal early intervention methods would be better than eye-drops in terms of preventing progression and reducing the need for major surgery, such as trabeculectomy.”

Fortunately, as Gallardo points out, intervention options have improved: “New products now allow us to safely intervene very early – we’re seeing a paradigm shift in patient care.” Radcliffe expects iStent infinite to significantly contribute to this step-change: “It will drive things forward, not least because of all the effort behind it.” The infinite also brings helpful practical benefits; Singh notes that reducing a patient’s medication burden by one drop may save the practice four minutes per patient visit: “This would significantly improve practice efficiency.”

That said, not all practices are aware of the potential benefits of MIGS – or that iStent is safe and effective enough to be potentially used as a first-line, standalone intervention. As Ahmed says, “This new era raises a new challenge, which is to make new interventional approaches available to all glaucoma patients, not just those undergoing cataract surgery. And this will require us to reconsider optimal patient profiles and management. In short, it will need a different way of thinking!”