The Long Haul
Three glaucoma specialists assess the potential of the FDA-approved bimatoprost implant
Felipe Medeiros, E. Randy Craven, I. Paul Singh | | Longer Read
The sustained-release bimatoprost implant – marketed by the trade name of Durysta – is indicated for open angle glaucoma and ocular hypertension patients who require intraocular pressure reduction. Following the FDA approval of this new drug delivery system in March 2020, we talk to three glaucoma surgery gurus: Felipe Medeiros, who was the lead investigator in the bimatoprost implant’s clinical trials, as well as E. Randy Craven and I. Paul Singh, who view the technology as a practice-changing innovation. The big question: will glaucoma treatment be transformed?
Let us know what your experience with the sustained-release implant has been like.
Felipe Medeiros, Distinguished Professor of Ophthalmology and Vice-Chair for Technology, Director Clinical Research Unit, Department of Ophthalmology, Duke University, Durham, North Carolina, USA
It is universally acknowledged that daily glaucoma eye drops constitute a treatment burden for many patients, causing issues with compliance and adherence to prescribed therapies – studies show that over 50 percent of patients don’t follow their prescribed topical medication regimes over 75 percent of the time (1). Eye drops can also contribute to ocular surface disease, with side effects such as itching or stinging. One of the innovations attempting to provide long-term lowering of glaucoma patients’ intraocular pressure – without the worry of poor adherence – is the slow-release implant.
Durysta is the first FDA-approved sustained-release intracameral implant tackling intraocular pressure in glaucoma. It is indicated for any patient suffering from open angle glaucoma or ocular hypertension who requires an IOP reduction, as long as they don’t have any contraindications (such as a history of angle closure or corneal diseases that decrease the number of endothelial cells).
I can see the implant having broad applications, and working very well for patients who have trouble with compliance to topical medications, and where the glaucoma specialist believes there is a possibility of lowering the IOP before reaching for more invasive interventions, such as a surgery (MIGS or trabeculectomy). The idea is that, by using a slow-release mechanism, the medication will achieve more sustained pressure control, avoiding peaks and fluctuations that can potentially lead to more optic nerve damage and vision loss.
Many of my patients don’t tolerate topical medications well and their ocular surface suffers. There are also those with limited mobility, including elderly patients suffering from rheumatoid arthritis, who have to rely on others to apply eye drops – the slow-release implant works well for them.
I was the lead investigator in the ARTEMIS clinical trials for Durysta, in which we evaluated 1,122 patients from 108 centers in 14 countries, comparing the implant’s safety and efficacy with that of twice daily timolol-containing eye drops. We found that Durysta lowered the patients’ IOP by around 30 percent, and the effect lasted through the chosen 12-week period (2). We designed the trials as non-inferiority studies and aimed to show that the implant did not perform any worse than timolol eye drops. However, what the trials actually showed is that the pressure lowering by the implant is greater than that of timolol, and comparable to what can be seen with a topical application of a prostaglandin analog like bimatoprost. In other words – its effect is similar to that of the eye drops, without the significant treatment burden, and with a longer-term pressure reduction.
The implantation procedure is quite simple and only takes a few minutes. The implant is inserted with the use of an applicator, with a 28-gauge needle, which is inserted into the anterior chamber. The implant is released and settles in the angle of the eye.
For now, the implant is FDA-approved for a single application, which will last for a limited time. There are additional trials taking place, and in the planning stages, to support an extension of the FDA approval for multiple applications, which I hope will greatly improve patient outcomes.
The Phase 3 clinical trials that I led included three applications of the implant, each lasting four months. We observed that after the final application approximately 80 percent of patients did not need any additional treatment for up to a year – a crucial finding that shows the potential long-term response.
We also observed that the rate of visual field loss for the implant group was slower than for the group using timolol topical medication. This news is huge; preserving visual function is the ultimate goal of glaucoma therapy – lowering or maintaining pressure is just a surrogate result. I consider these to be very powerful results and they give me hope for the future of glaucoma management.
E. Randy Craven, Associate Professor of Ophthalmology at Johns Hopkins University, and Chief of Wilmer Eye Institute in Bethesda, Maryland, USA
I have a long track record with Durysta. When it was first being developed, I was one of the first consultants who took part in running test models, and in conducting the first in-human trials. I have been part of Phase 1, 2, and 3 trials – and I’ve watched the implant develop over that time.
We found that many patients had an extended pressure-lowering effect after just one implantation – for 28 percent of patients, this lasted up to 24 months, and for 68 percent of patients, it lasted for six months (2). The FDA approved it for a single injection based partly on that, and partly on the need to further evaluate long-term corneal safety with multiple injections, when multiple implants touch the endothelium.
My colleagues and I have been identifying patients with open angle glaucoma and healthy corneas, who suffer from corneal irritation caused by preservatives in topical medications, or who have issues with adherence. Some of them have a tremor, which makes instilling eye drops difficult; some suffer from early dementia and forget to use their medication. Those patients are usually on one or two medications, and they are excited to hear that there is now another option available in the form of an implant.
Many of my colleagues perform the procedure at the slit lamp, with topical anesthetic, using the same protocols as for intravitreal injections. The patient looks straight ahead and the physician comes in from the side, with the applicator needle gently entering the anterior chamber, before pushing the button to release the implant.
I use the minor procedure room for the implantation, but it is purely down to my personal preference. The patient lies back and I insert the implant – for the right eye, I sit above their head, and for the left eye, I sit temporal to them – then sit them back up and check the implant. I look for any leakages and ensure the implant is in the right position. I follow up with patients after a week and after a month, and then check their IOP every three months.
From what I have seen in the last few months, the COVID-19 pandemic has had a huge impact on the severity of glaucoma in patients reporting to ophthalmic practices. Patients classed as glaucoma suspects have not been coming in for check-ups, as the risk was deemed too great. Now, we are back in the clinic, and I’m seeing many more of these patients. It gives me a little more comfort knowing that with the slow-release implant, patients are not required to visit the ophthalmic practice as often, and the medication is still being delivered to the eye, for months at a time. However, I can see an issue with not knowing how long the pressure will be kept in check if patients are not seen regularly. Right now, it is difficult to see patients implanted with Durysta every three months, as my schedule is very full, and we are not back to full capacity due to COVID-19 safety protocols.
Glaucoma specialists who haven’t tried the implant yet, should be encouraged to use it in their practice. My advice is to allocate time at the end of the day or half a day in the week when they can perform a few of these implantations, as it can be difficult to find the time to start implementing a new strategy in the middle of a busy clinic. I have a “Durysta day” when the room is ready, the patients scheduled, and I can focus on implantations, without worrying that I’m going to lose time meant for my other patients.
The logistics of adding the implant to the particular practice’s portfolio might seem overwhelming at first: there are prior authorization issues, working out insurance billing, buying the implant and keeping it in stock, but it is worth the initial hassle. For the procedure itself, practice protocols already used for injections will generally be applicable and very safe.
I’m really looking forward to future, larger studies. We have noticed during the clinical trials that visual field sensitivity decreased for control patients using timolol eye drops – a fairly typical outcome for people with mild glaucoma. For the patients implanted with Durysta, visual field sensitivity remained stable. The around-the-clock action seems to have a better mechanism for pressure control. This is very encouraging, and I’m looking forward to seeing further evidence of this from upcoming trials.
I. Paul Singh, President of The Eye Centers of Racine & Kenosha, Wisconsin, USA
The most difficult issue I face in the management of glaucoma is trying to maintain stable IOP. We are seeing a huge emphasis on improving compliance – problematic due to medication costs, side effects, or simply patients forgetting to instill eye drops – often with a surgical intervention mindset. And I think that’s why MIGS and SLT are generating such a buzz of excitement. Early intervention is now seen as crucial.
Durysta is a new addition to the glaucoma specialist’s toolbox, helping us intervene earlier and maintain a stable IOP, while overcoming compliance issues. It is a very flexible solution that can be used in a variety of different settings, from a hospital to a community-based practice or office (differentiating it favorably from MIGS). Provided there is good head stabilization, good magnification, and good aseptic conditions, the procedure is safe to be performed anywhere.
Expectations for a standalone procedure, as opposed to a MIGS procedure combined with cataract surgery, are high – and the implant delivers on its promise of lowering the IOP. It is applicable to any type of disease state, from mild to advanced glaucoma.
Durysta helps surgeons hedge their bets and attempt to achieve freedom from eye drops for patients before or after reaching for MIGS. It can also be an intermediary step to give patients’ ocular surface a rest from topical medications containing preservatives. I use Durysta for my cataract surgery candidates with an unhealthy ocular surface to give it a chance to restore, so that I can obtain better biometrics and get better results after the surgery.
For some glaucoma specialists, not keen on using MIGS or glaucoma surgery in general, trying the implant might be the first step towards the interventional mindset. Implanting Durysta is a very straightforward process that any ophthalmologist can learn very quickly.
Additionally, Durysta does not cause the adverse effects typically associated with topical prostaglandin analogs, such as periorbital changes in pigmentation, meibomian gland dysfunction, and other issues.
I have been surprised by the uptake and the wide adoption of the implant, but it makes sense when I consider compliance issues and the fact that it is fully covered by insurance (it can be cheaper for the patient than using generic glaucoma medications). As many specialists now perform the implantation at the slit lamp, from the patient’s perspective it is a very straightforward procedure, and it brings down their defense mechanisms – it is seen more like a regular check-up than a surgical procedure.
As with all glaucoma interventions that do not rely on patient compliance – such as MIGS or SLT – with the implant, the patients’ visual field mean deviation is better (2). Even if the effect is not obvious straight away, over months and years it is improved, compared with the cohort using topical medication. For some patients there might not even be a big change in the IOP, but there is clearly more stability in the visual function.
I feel comfortable implanting Durysta in phakic patients – in fact, 75 percent of patients in the Phase 3 trial were phakic. The procedure is great for younger patients, where we want to avoid using topical drops altogether for as long as possible, and keep the ocular surface healthy.
Many of my patients are now afraid to apply their eye drops, or even to go to the pharmacy to pick up a prescription. Many of the more vulnerable patients relied on others to instill medication, and those relatives or friends might not be able to see them in person at the moment. The slow-release implant removes many of these pandemic-related worries out of the equation. Patients don’t have to worry whether they’ve washed their hands well enough before applying eye drops, or whether their relatives might not be able to visit because they work in high-risk settings or they’re having to self-isolate.
As a care provider, I don’t have to worry about compliance, whether my patients can get a refill or if they decide to buy a generic drug rather than a specific brand. All these variables can result in intraocular pressure fluctuating. And that’s why I have appreciated being able to offer Durysta to my patients during the COVID-19 pandemic.
I’m excited to see how Durysta works before or after SLT. Only 5 percent of patients in the trials had previously had SLT, so there are many unanswered questions on how this might affect the disease state itself.
Getting the implant approved by the FDA for multiple applications will be a great next step. It will give us a new understanding of how long the implant can last for. If there is constant, slow release of medicine intracamerally 24 hours a day, as opposed to once or twice a day topically, could this be changing the pathology itself? We might be able to answer that question soon, which is very exciting. From the clinical trial results, it seems that the more implants we use, the more longevity the therapy has, and only a smaller percentage of patients might require rescue therapy.
I’m already implanting a variety of my patients – from mild to advanced glaucoma – and monitoring the duration of the implant’s effect very closely. For some patients, pressure might be lowered for four months; for others, the effect lasts for two years. Once multiple implantations are approved, the experience of using the implant in many different scenarios will give me a better plan of action for each individual patient – making it easier to work out how much time I should leave between check-ups, and between implantations.
Having Durysta as a new tool in our armamentarium is another step in the direction of wider adoption of the idea of early intervention, taking the issue of compliance out of the equation. This change of glaucoma specialists’ mindsets will result in better IOP stability for our patients, and – ultimately – greatly improved outcomes.
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- A Robin, DS Grover, “Compliance and adherence in glaucoma management,” Indian J Ophthalmol, 59, S93 (2011). PMID: 21150041.
- FA Medeiros et al., “Phase 3, randomized, 20-month study of bimatoprost implant in open-angle glaucoma and ocular hypertension (ARTEMIS 1),” Ophthalmology, [Online ahead of print] (2020). PMID: 32544560.