Pressure Point

Patient compliance is essential to ensuring that prescriptions can actually have an effect. Compliance is a common problem across all fields of medicine, but is notorious in eye care, especially when looking at eye drops (1). In my practice, compliance is the biggest issue I face in the medical management of glaucoma. Poor compliance can lead to the potential for fluctuating intraocular pressure (IOP) and or an inability to reach target IOP. Fluctuation can be a risk factor for progression over time, as demonstrated in the AGIS study (2).

I’d like to share my experience of patient care following implantation of Durysta to reduce IOP, which I had previously used during its phase II and III trials. Last June, I finally got the chance to use the product in a real-world setting on a 68-year-old Medicare fee-for-service patient with mild peripheral open angle glaucoma (POAG). He was suffering with significant ocular surface issues, couldn’t remember to take his topical medications, and would also skip drops to save money. His medical history included two sessions of selective laser trabeculoplasty (SLT) and he was back on a daily generic prostaglandin analog (PGA) and beta blocker for both eyes. A regular complaint was that his vision would fluctuate throughout the day and eye drops caused red and watery eyes; additionally, he admitted to mostly using his drops in the few days leading up to an appointment. Not all the news was bad, though! His Humphrey visual field tests were full and stable and he had a fairly healthy retinal nerve fiber layer (RNFL), minimal ganglion cell complex (GGC) loss, only slightly low corneal hysteresis, and central corneal thickness (CCT) in the 530s.

In-office IOP measurements were at target in the teens, but did fluctuate by around 4 mmHg between visits. His BCVA was 20/20 with a very early nuclear sclerosis lens change that was hard to detect due to poor tear film breakup time and meibomian gland dysfunction with significant corneal staining. We had initially prescribed topical cyclosporine and artificial tears – but, with the patient already struggling to use eye drops for glaucoma, adding extra drops to the list was fruitless.

This led me to ask, “Is this patient controlled? Should I continue with the course of treatment when compliance issues are so pervasive?”

One way to define patient control for glaucoma is to look at the patient’s IOP, visual field, and disc stability alone – in which case, my patient could be considered controlled. But, in my opinion, if a patient has a low likelihood of continuing a therapeutic regime due to compliance issues – whether that be cost (which studies have shown can prevent initial prescriptions from being refilled), side effects, ocular surface disease (OSD), forgetfulness, or other reasons – that patient is not controlled.

Taking compliance into account for my definition of controlled glaucoma has been a big philosophical change and it is a core tenet when I think of the term “interventional glaucoma.” We have to remember that glaucoma is a progressive disease and it is often difficult to see changes early on. For instance, in the OHTS study, the delta between the two groups did not diverge significantly until after five years, at which time untreated patients’ rates of progression rose significantly faster than those who were treated (3). Intervention to maintain a high quality of life and substantial compliance to help preserve nerve structure and function are my goals.

Dry eye is common in glaucoma patient populations, but so is poor compliance with drops (4). This can lead to fluctuations in IOP – a risk factor for progression over time – and it is clear that untreated patients have much higher rates of disease progression.

Due to the lack of compliance and the previous SLT treatments, I offered my patient MIGS – but the prospect of surgery made the patient apprehensive and he chose to wait. A short time later, Durysta was approved. I explained that the medication he was taking is now available as a dissolvable slow-release material that can be placed in the eye in-office using the same lamp that I use to check eye pressure. Because the drug is released inside the eye bypassing the barriers to absorption, and is released nearer to the biological target, a much lower dose is needed for therapeutic effect. Durysta is also approved for a single administration, releasing medicine over four months, but the duration of effect can last much longer. Based on the Phase 1/2 trials, with a single administration, the IOP-lowering effect has a 33 percent chance of lasting for a year and a 25 percent chance of lasting two years (5). A possible explanation for this duration of effect is a potential to modify the resistance of the disease by increasing the expression of MMP and decreasing the expression of TIMS.

The patient decided to go ahead with Durysta – which is inserted in an office or ambulatory surgical center either with the patient in supine position or at the slit lamp. We decided to insert at the slit lamp in both eyes. For a procedure like this, aseptic conditions are crucial to avoid infection; we used betadine to clean the eye, sterile gloves, a technician to keep the patient’s head stable, and had the patient fixate on one of the slit lamp knobs. I entered the eye anterior to the limbus just below three o’clock of the left eye and nine o’clock of the right eye, staying over the iris, and then depressed the button on the loader to release the implant. The patient couldn’t believe that both eyes were implanted in the exam room without any discomfort. I’m routinely told, “Doc, that was easier than getting my eye pressure checked.”

One pearl of wisdom I can offer to others is to press the injector button halfway until you see the implant partially exposed, then fully depress. This allows the fluid to absorb any air bubbles and ensures that the implant will be released completely free of the needle (double-press technique).

Patients don’t tend to be bothered by IOP reduction lasting only four to six months – and a second injection has not been approved by the FDA at this time. The reason for patients’ relaxed attitudes is that I present the therapy as a “drug holiday” – patients can take a break from the daily treatment regimen that is part and parcel of glaucoma management, thereby solving compliance issues for the duration of drug activity. Due to the high safety and benign nature of the insertion, the bar to acceptance and success is much lower than that of a surgical option. In fact, for this patient, there were no out-of-pocket costs because he had Medicare fee-for-service with a supplement. Even if he has to go back on drops, we at least saved him a significant amount of money for a period of time.

The patient is now 10 months post-implant and his IOP is still in the 16–17 mmHg range – allowing him to stay off both PGA and beta blockers. I have been pleasantly surprised to see many patients maintain significant efficacy beyond six months and, likely due to compliance, able to remove more drugs than just the PGA. In fact, looking at our own data, over 90 percent of our patients have demonstrated efficacy beyond six months. A few have now seen a slight rise in IOP compared to topical medication, but most are still within the target range. I still feel comfortable observing those with IOPs 1–2 mmHg higher because I know there are no compliance issues to deal with and thus possibly less potential for fluctuation. The studies also demonstrate that IOP doesn’t rise back to baseline immediately; there is a slow rise that provides time to see the patient again depending on the severity of their case.

On my patient’s last visit, I told him that if his IOP is higher at his next visit, he may have to start taking the eye drops again. Surprisingly, he said, “Doc, now that I have had this time off from my glaucoma drops, my eyes feel so much better. I think I’m ready to have that glaucoma surgery you mentioned before.” This kind of response is increasingly common from patients who initially refused MIGS-type procedures. After having a “drop-free holiday,” patients express more openness to pursuing surgical interventions. It’s almost as though Durysta has served as a mental bridge between drops and surgery – providing them with perspective on reducing the drop burden and appreciating the potential longer-term benefits of surgery.

Now, over a year of implanting Durysta, we have found that patient acceptance is often based on their level of compliance issues. We have also had a wide range of patient types across mild, moderate, and advanced disease; we have implanted in patients with OSD, ocular hypertension, those on the way to a subconjunctival or tube procedure, and post-SLT or MIGS. Even with this diverse range of patients, we have not seen any adverse events to date in my practice.

We now have more options than ever before for surgeons and patients alike – and these safe and efficient interventions have forced me to reevaluate my processes. Can we now truly customize our therapy? Can we now combine technologies and mechanisms to help to maintain or improve quality of life while adequately controlling IOP? I have realized that, the earlier we intervene, and the higher the target IOP, the better the chance that less invasive options will succeed and keep patients functioning at a high level.

The author reports that he is a consultant for Ellex.