Evolving glaucoma therapy: A new era of interventional strategies

Inder Paul Singh, MD, from The Eye Centers of Racine and Kenosha, Wisconsin, recently moderated an Ophthalmology Times Case-Based Roundtable that addressed the new playing field in glaucoma care. For Singh, the term interventional glaucoma no longer means having to choose between being aggressive with IOP reduction and doing it safely, or having to choose between addressing adherence-related issues and doing it safely.

“We can do both now, and it incorporates new technologies for earlier treatment. The earlier we treat, the better chance we have of achieving that target pressure, the better chance we have of minimally invasive procedures actually achieving our goals, ie, decreasing the IOP to the target range and reducing the medication burden,” he said.

Along with the more aggressive approach to glaucoma has come a refinement of the definition of the term glaucoma control. The definition has moved from hitting the target IOP with acceptable appearances of the visual fields and optic nerve to considering quality of life and the ability for someone to stay on the current treatment regimen long term.

Ophthalmologists know from studies like the LiGHT trial (ISRCTN32038223), which compared selective laser trabeculoplasty (SLT) as a first-line therapy with eye drops, that despite the same average IOP reduction in both groups of patients, after 6 years, those who underwent SLT had less disease progression compared with eye drops, Singh noted.

What are clues to patient adherence?

There currently is more attention to details over and above the target IOP.

“If patients are nonadherent and if IOPs are fluctuating, there is a higher risk of progression. If pressures and fields are stable, but the patient has red eyes or there are cost issues or forgetfulness, these are other barriers to adherence. These patients are uncontrolled,” he said.

When attempting to identify nonadherence, Singh advised paying attention to clues such as the patient not remembering the drug name or the color of the bottle top. In addition, asking for samples at each visit may indicate that cost is an issue and that patients may be stretching the eye drops and not instilling them daily. Complaints of fluctuating vision may indicate dry eye caused by preservatives.

Replacing eye drops

These clues indicating nonadherence may be key in suggesting an alternative treatment to help the patient stop using eye drops, thereby reducing the treatment burden through a sustained-release device or a procedural pharmaceutical. Implanting a drug delivery system might be an opportunity to eliminate the barriers to patient adherence.

Two sustained-release procedural pharmaceuticals or drug-delivery options are available in the US: the bimatoprost intracameral implant (Durysta; AbbVie) and the travoprost intracameral implant (iDose; Glaukos).

Bimatoprost intracameral implant

This is a biodegradable implant that degrades into lactic acid and glycolic acid and releases bimatoprost over a 4-month period. The device is inserted through a clear corneal incision during an in-office procedure.

“The key was recent longevity data from the ARGOS study [NCT04647214] that showed we have from 1 year to 18 months of efficacy in about 78% of patients with 1 implant. The theory is that maybe we have longevity because we’re changing the actual disease process,” Singh said.

He theorized that with a 24-hour-a-day release of bimatoprost, studies have shown overexpression of metalloproteinase (MMP) and decreased expression of the tissue inhibitor of MMP.

“With constant increased MMP expression, are we releasing these cytokines and interleukins like [with] SLT? Is this opening up the scleral, uveoscleral pathway, and trabecular meshwork, by keeping it open 24 hours a day? Are we changing the actual morphology of the disease? This longevity has been documented multiple times in multiple studies,” he said.

Travoprost intracameral implant

The roundtable participants discussed the course of treatment in patients for whom the effects of a sustained-release device decreased over time and the IOPs increased, but the patients return with a cataract and are back on eye drops.

This scenario presents an opportunity to both extract the cataract and perform a minimally invasive glaucoma surgery (MIGS) simultaneously, such as stenting, canaloplasty, or goniotomy. A drug-delivery platform, such as the iDose, which is a canister that is secured into the scleral wall nasally, also can be used at the time of cataract surgery. One characteristic of the iDose is that it needs to either go through the canal or be seated in a specific spot anywhere in the nasal angle. If it goes into the scleral wall, it is stable, Singh noted.

The iDose releases a proprietary oil over time and has shown a 2- to 3-year efficacy. Almost 80% of patients used the same or fewer medications at 3 years with 1 iDose insertion. One study also found that when the canister was removed early, a significant portion of medication, about 16%, was still present at 2 years, he added.

“This technology presents an opportunity for us to use drug delivery and MIGS procedures at the time of cataract surgery,” he said.

The iDose also can be used as a standalone in pseudophakic patients who have undergone SLT and are on 2 or 3 medications for moderate glaucoma. An option would be to perform canaloplasty, a stand-alone stent, and then an iDose at the same time. He explained that having a prostaglandin in the eye eliminates concerns about resistance to outflow or incorrect positioning of the stent and possible increase in IOPs.

Many ophthalmologists are more comfortable doing stand-alone MIGS, especially with concomitant use of a procedural pharmaceutical to get that 30% pressure reduction that the prostaglandins provide, Singh noted.

“At this time, we have a lot of opportunities. SLT as a first-line treatment makes a lot of sense because it addresses the actual pathology,” he said. “We also have procedural pharmaceuticals as a stand-alone or at the time of cataract surgery and a MIGS procedure.”

These concepts can achieve significant IOP reductions and avoid the need for some more traditional surgeries, such as trabeculectomy and subconjunctival minimally invasive bleb procedures, Singh added.

“If we can provide drug delivery and SLT early, we may be able to kick the can down the road farther or even limit the need for those other more invasive types of procedures over time,” he said. “Not waiting for disease progression and using these new technologies early can really help prevent progression for a lot of patients.”