The Missing Middle Ground in Glaucoma

What are the unmet needs in glaucoma?

Inder Paul Singh: We have so many patients handcuffed to their medications – facing a lifelong sentence of eyedrops. Studies show that compliance is poor, and gets worse as the number of eyedrops patients take increases (1). We don’t have many alternatives for those with mild-to-moderate disease. As surgeons, we know the risks of traditional glaucoma surgeries. This means we’re faced with patients who are suffering with drops: they struggle with the costs, side effects, enforced daily routines, and the worry of forgetting to take them. But we simply have to say “Too bad. You have to stick with them, because I don’t want to push you to have surgery that may cause other issues in the future.”

John Berdahl: For patients with mild-tomoderate glaucoma who don’t tolerate drops, there isn’t really a middle ground – until the advent of MIGS, we had to move to bigger surgeries. But although traditional options like trabeculectomy can do a good job of lowering IOP, we know they come with significant risks: the failure rate is high, and patients face postoperative eyedrop regimens and potential healing issues.

What are the current alternatives?

IPS: MIGS procedures offer a good alternative to more invasive surgery. These carry a more favorable adverse event profile, allowing us to treat patients who would otherwise be kept on meds. But there’s still a problem: we don’t have a great understanding of where the resistance to outflow is preoperatively. With a trabeculectomy or tube surgery, you’re bypassing the natural drainage system, so it doesn’t matter where the resistance is. With certain MIGS procedures that work on improving natural outflow, the location of the resistance – which can be at the juxtacanalicular tissue, or more in the canal of Schlemm, or even distal to that – can vary from patient to patient. So a MIGS procedure, depending on where its main mechanism of action is, could have far less of an impact than hoped.

JB: The microinvasive surgery space is rapidly expanding to fill the void, but the problem isn’t solved yet. MIGS is usually performed alongside cataract surgery, so consequently the labelled indication for most MIGS devices in the US is in combination with cataract surgery. If you’ve got a pseudophakic patient, and you want to lower their IOP, but don’t want to progress to more invasive surgery, you might have to take an off-label approach, and reimbursement may or may not follow. Also, some options offer better efficacy than others – there are some patients in which I’d like to lower IOP more than these options can offer, and I’d be willing to tolerate a little more risk, while still avoiding a more invasive procedure.

Where do the opportunities for improvement lie?

IPS: Being able to take patients off medication can have a very positive impact, especially on those who find it burdensome. Ideally, we would be able to intervene earlier. Not only will that help keep patients off drops – in a disease state like glaucoma, the earlier you take care of it, the less need there is to treat it aggressively later on. The more advanced the disease, the more nerve damage and retinal ganglion cell loss we have, the lower the target pressure we have to aim for to maintain what’s left. In other words, earlier intervention provides a better chance of halting progression and lowers the likelihood of the patient needing future treatments like invasive surgery, or even more eyedrops. Personally, I don’t ask which patients are good MIGS candidates – I ask which ones are not, since the benefits far outweigh the risks. This is a change in paradigm, and early surgical intervention is a change we could see sooner rather than later. I’d also love to see more work on preoperative assessment of outflow, to help us choose the right MIGS device or procedure for a specific patient; in other words, more “targeted MIGS.”

JB: A good procedure would be one that can be used in pseudophakic patients who don’t need cataract surgery, but won’t cause reimbursement issues, and it could provide more IOP lowering than something like a trabecular bypass stent. This may mean you have to be willing to tolerate a slightly increased risk of postoperative hyphema, but for patients who need their IOP lowered that little bit more, it would still be a reduction in risk compared with traditional surgery.