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Expert Views: Using Surgical Approaches for Neovascular Age-Related Macular Degeneration in Practice

Authors: Clare Bailey, MD, FRCOphth; David Brown, MD; Roxane Hillier, MBChB, FRCOphth; Nancy Holekamp, MD; Laura Sararols Ramsay, MDFaculty and Disclosures


Activity Transcript

<< SEGMENT 1 >>

Clare Bailey, MD, FRCOphth: Hello, I'm Claire Bailey, a consultant ophthalmologist and lead of clinical research at Bristol Eye Hospital in the UK. Welcome to this activity, “Expert Views: Using Surgical Approaches for Neovascular AMD in Practice.” Today, we are planning to cover emerging surgical techniques for the management of neovascular age-related macular degeneration (AMD), which will include the evidence base, surgical tips and aspects related to patient education.

Although the current anti-vascular endothelial growth factor (VEGF) treatment regimes have transformed the clinical outcomes for patients with neovascular AMD, they do require regular assessment and re-treatment. This is very burdensome for this elderly group of patients to have frequent visits and injections, and also creates a large capacity-demand for the delivery of care. There's been considerable research into finding longer acting solutions and there are a number under development.

This activity will discuss the port delivery system (PDS), which has FDA approval and has been in use in the USA, is also under regulatory review with the EMA. This is surgically implanted into the eye and slowly releases the anti-VEGF medication ranibizumab over many months. Refilling of the device is required periodically. At the time of this recording, this has been temporarily withdrawn from use by the manufacturer to further investigate aspects related to septum dislodgement during the refill procedure.

The forthcoming talks will describe the evidence base, the techniques for surgical placement and the refilling procedure, as well as aspects related to patient education so that they are very well informed about their treatment choices. The talks will also cover the current research evidence and surgical approaches for gene therapy for neovascular AMD. This can lead to local production of anti-VEGF within the eye, either ranibizumab or aflibercept depending on the particular study, and techniques may involve subretinal or suprachoroidal delivery.

So, our first talk will be from Laura Sararols Ramsey, who will give an update on the current evidence. Then we'll hear from Roxanne Hillier, who will give some experience from the United Kingdom. David Brown and Nancy Holekamp will then give their experience from the USA, and follow that with a discussion about patient monitoring.

Thank you for your attention. Please watch the next segment with Dr Laura Sararols Ramsey.

<< SEGMENT 2 >>

Laura Sararols Ramsay, MD: Hello, I'm Laura Sararols Ramsay. I'm a retina specialist. I'm also a Vitreo-Retina surgeon. I am based in Barcelona, in Spain, actually at the north of Barcelona. And I want to welcome you to this segment. It is, "Data Update in Surgical Approaches to Neovascular AMD."

Okay. The technological approaches to neovascular AMD: we all look for a better durability. So now, we have the FDA-approved PDS implant with ranibizumab. But there's also other surgical approaches that are investigational that are still in the pipeline and that we hope to be able to use in the future: these are via gene therapy and also other technology that's being studied that's the tyrosine kinase inhibitors (TKIs) and the biopolymers. We'll talk mostly about the PDS with ranibizumab.

We have the phase 3 trial, Archway, which is completed, and we have 2-year data. And also, we have the extension portal study that's still ongoing and that we do have some data available that we will review now.

So, the PDS as most of you know, it's the port delivery system. It's a surgically implanted device in which we have to take the patient to the operating room (OR) that we have to implant this small device with a retrobulbar anesthesia for example. And this device 'lets go' a sustained release of anti-VEGF (exactly, it's ranibizumab) into the vitreous cavity. It was approved by FDA in 2021. So, we do have a big amount of patients that already have this implant and the refill is quite comfortable, because this refill/exchange is plan to do in the clinic every 6 months. So, that allows a very good control of the neovascular AMD without the spikes that we do with the injections and without the weeks where the patient doesn't have any anti-VEGF in the eye. So, it allows us a much better control and much chronic control of this chronic disease.

In the study Archway, that was the phase 3 trial on neovascular AMD for the PDS, we have the 2-year data and that was the end of the study. 415 patients were implanted. They were in 2 arms: 1 arm was with PDS, it had ranibizumab and was refilled every 24 weeks, and the other arm was with injections of ranibizumab every 4 weeks. This was the treatment period and then there's an extension and a final visit at the end of the week, 96 was 2-years of study.

We have a very good results because in 90% of the PDS arm, they completed the treatment versus 92% with ranibizumab. So, we don't have to look for explanations of patients that were dropouts. There was the same number of dropouts in 2 arms.

If we can talk about what the sensation of the patients were when we ask in that study, when they asked the patients what did they prefer, what did they, they were patients that had injections before, what did they prefer? Well, 93% of the PDS patients they preferred the PDS, although that is a surgical implant and they knew the risk of that, but they preferred that over the injections.

And the adverse events (AEs) were not... Very significant. They're also, there evidently is a surgical implant, so there can be some complications, but there was just 1.6% with of endophthalmitis in the PDS group versus 0.6 in the ranibizumab injections. And vitreous hemorrhage is 6% in the PDS (is a more percentage evidently) versus 3.6% in the ranibizumab injections group.

The results, the anatomic results are really good. We can see a very constant control anatomically, with the central subfield thickness (CST), as you can see here in both groups. Actually in both groups, we have a very stable and chronic control of the disease that is really, really good and that we can see the anatomic results are good.

So, evidently the visual acuity, as there's no important <indecipherable>, the visual acuity is also very well stable and controlled in the 2 years of the study.

Having the portal extension 3-year data, it's important that we talk about the ocular AE because, as I said before, it is a surgical approach and we are all worried about the safety of any implant in the eye. And we do have some patients that did have some AEs. And these AEs that really worry us as surgeons would be, for example, endophthalmitis or an implant dislocation, rhegmatogenous retinal detachment. The proportion of patients that have these worrying AEs have been in the portal extension data were 6 patients (that is 2.4% of patients) had an implant dislocation. For endophthalmitis, for example, it was a total of 5 patients (that's a 2% percentage of cases). And the rhegmatogenous retinal detachment was only in 2 patients, for example, so that would be a 0.8%. So the AEs can appear, but the proportion of patients that have worrying or sight-threatening threatening ocular AEs, the proportion is low. So we do have to take it into account, but it's not something that should preclude us of being safe or explaining to our patients when to use PDS.

As I said before, when we ask the patients if they prefer the PDS or they prefer the injections (as the patients had experience) they 88% prefer the PDS.

Okay. We've talked about PDS and now we're going to talk more about the future. So, PDS is FDA approved. We already have a lot of patients with that therapy and we will continue using it in the future, but we also have to know what is in the pipeline and what will be in the future.

In the future. We have these investigational therapies that work through gene therapy, so we call them kind of a biofactory. So, what we are trying to do is getting the eye to produce their own anti-VEGF. So, that would be just fantastic to find, no, we haven't eye with the disease. So, if that same eye can, the cells in the eye can produce their own therapy. So, that would be just fantastic. So, here we have 2 main lines.

So, we have the RGX 314 that is an adenovirus that encodes for an anti-VEGF, similar to ranibizumab. So, we're trying to get an eye to produce ranibizumab. And we've had different trials that do show us that that is possible and that allows us to get control of the disease also. So, the RGX 314 has been tried in a subretinal approach and also in a suprachoroidal approach.

And actually the phase 2 AAVIATE is ongoing. The results seem to be quite good and there's also a phase 3 already ongoing. And in the future we'll hope to have very good results. So, in the AAVIATE trial, we are using the suprachoroidal space to inject or to get this adenovirus, to get the gene therapy to this retinal cells and to express this anti-VEGF similar to ranibizumab. So, the results of the AAVIATE study, although it's not very a big amount of patients is only 30 patients where we see that treatment is very well tolerated, that safety is very important for these initial studies. They were 4 serious AEs (SAEs) but they were not drug related. And that allows us to get a stable vision and really the treatment burden for these patients and for doctors is less.

The ADVM-022, that is something similar also with the adenovirus, it's the approach is intravitreal and here the target is the retinal cells: they will express aflibercept. So, this is the Optic, it's a phase 1/2 trial and it is ongoing.

The RGX 314 is approached, as I told you, as a suprachoroidal approach. So actually, I'd like to comment that the suprachoroidal approach, the suprachoroidal space is something that's in the future will probably will be hearing about it. And I hope we'll be hearing good results about it because it's a space, it's a virtual space that we can use to implant different medications for different diseases. So, it's a very good approach. It's an approach that can be done in the office. We don't need to do go to the OR and if in future trials if we can get good results, well that would allow us a very good future for our patients with neovascular AMD.

Also in the future, I think what we also have to improve not only gene therapy and surgical approaches, we also have to improve in the early diagnosis and early intervention for neovascular AMD because as we all know, if we detect the neovascular AMD really early and we have a good control of the disease, the patient can have good vision for a long time. But if we have a lot have surgical approaches and we have new therapies, but we are not capable of detecting and diagnosing this neovascular AMD at the beginning, the patient will not be able to maintain good vision. And that is also very important, and I hope that will also improve in the future.

Thank you for your attention. I hope you enjoyed it. And if you go on to the next talk, you'll hear Dr Hillier, she's going to talk about the surgical approaches and there'll be other more practical talks about the implant of the PDS. Thank you.

<< SEGMENT 3 >>

Roxane Hillier, FRCOphth: Hello, I'm Roxanne Hillier, a consultant ophthalmologist and vitreoretinal surgeon, and Research Lead for Ophthalmology in Newcastle upon Tyne, the UK.

So welcome to this segment, Experiences From the UK. I'm going to talk about my early experience of implanting the port delivery system, and my thoughts about its potential place within the UK AMD population. So by way of perspective, I have implanted 4 devices so far, and I've had the opportunity to follow up my patients over a 6- to 8-month period, as part of the VELODROME trial. So I can therefore share with you my initial impressions and early learning curve, in terms of surgical implantation.

In terms of the patient's perspective, I find that the port delivery system has been received with really great enthusiasm, and recruitment into the study has been very brisk. My patients seem satisfied, with comments such as, "Can you implant one in the other eye please?"

From the surgeon's perspective, I was very keen to be an early adopter of the device, because of the potential to reduce the treatment burden for patients with AMD. I also thought that potentially, the stable dose administration from a sustained delivery device was compelling, in terms of disease control.

I naturally have concerns, had and have concerns, about the potential harms of the device, and I'm very keen to mitigate these. And in terms of the surgical implantation, it's interesting and novel for a retinal surgeon in some ways; but the procedure is systematic, standardized, and supervised and supported quite closely by the sponsor. So the learning curve has been quite swift, and not too challenging.

So in terms of patient selection, the VELODROME trial mandated a demonstrated response to the loading dose of anti-VEGF agent before considering implantation. When considering whether or not a patient is suitable for implantation, we need to do a very careful and conscious ocular examination of the lids and periocular skin. For example, evidence of blepharitis, trichiasis, lagophthalmos, habitual eye rubbing, scarred conjunctiva (for example, previous strabismus surgery, or chronic use of multiple glaucoma medications). All of these factors may increase the likelihood of conjunctival complications, such as retraction or erosion, which would predispose to sight threatening problems, such as endophthalmitis. Very important to identify before implantation. Things such as scleral thinning would make secure implantation of the device potentially tricky. And it's also important to have a good view of an intact healthy peripheral retina. So you do need a grossly clear ocular media, so you can monitor the retina and the device postoperatively.

In terms of systemic complications, these are geared towards reducing the risk of intraocular hemorrhage. So if a patient is on anticoagulants, we might, in conjunction with their physicians, temporarily stop these, or reduce the dose of these. Or certainly be mindful that, if they are on anticoagulants, the risk of vitreous hemorrhage after implantation is higher. And also, an uncontrolled hypertension would certainly be undesirable.

So I'd like to talk through some tips and tricks about the surgical implantation, with a series of videos that I'd like to share with you. This is a video demonstrating the surgical setup for implantation. As you can see, there is a traction suture, to help exposure of the supratemporal quadrant (that's often where the implant will be sited). I'm creating a 6 by 6 mm conjunctival, and crucially, Tenon's flap, with very generous undermining. The idea here, is to reduce any traction on the ultimate closure of the conjunctiva and Tenon's, to reduce the risk of subsequent retraction. Very careful hemostasis. And just note, that there is a 25 gauge infusion sited there. This has been sited and turned off, ready in case the eye becomes hypotonous in the moments after implantation.

So this next video clip demonstrates the scleral dissection. This is a 3.5 mm incision. Very important that this is precisely 3.5 mm, because this is likely to reduce the likelihood of implant dislocation at the time of refill. This is carried out using a microvitreoretinal (MVR) blade, to achieve the square edges all the way down to the choroid. Very careful hemostasis throughout, because the next stage does involve an incision into the vitreous cavity. And if there's any oozing of blood, oozing hemorrhage in the corners of the incision, this is likely to enter the vitreous cavity. And vitreous cavity hemorrhages were a complication in some of the earlier trial patients. And this is me just checking that I've not gone beyond 3.5 mm.

A further step to reduce the likelihood of vitreous cavity bleeds during implantation is this application of laser on the bared choroid before the incision is made.

Now we move onto insertion of the device. So I've used a 3.2 mm keratome there, being very careful not to inadvertently extend the wound. You can see, there was a little bit of hemorrhage at the end of the wound there, which I quickly cauterized, so that none of it went into the vitreous. You can see a knuckle of vitreous presenting here, which I'm tidying up using the 25-gauge cutter. And then, the device is implanted. It's okay to twist as you go in. Sometimes it's helpful to pop the infusion on as the eye becomes soft, just to help the device be sited. And there, I release the implantation device, and that's the device in situ.

Next is a seemingly simple but absolutely crucial step of conjunctival and Tenon's closure. So as I mentioned, conjunctival retraction and erosion were important, and very undesirable complications that have been reported in some of the earlier trials. And so, it's very important to close the conjunctiva and Tenon's in such a way that there is no traction on the wound. And you can see here, that the conjunctiva and Tenon's flap really hugs the limbus with some redundancy there; hopefully, to counter any subsequent retraction as the wound heals.

So moving on to tissue healing after implantation. This is the same patient 4 weeks after implantation. You can see that the device is visible through the conjunctival flap. And you can see with the fluorescein staining that there is no erosion, and quite a smooth conjunctival contour over the implant, which is desirable.

So if we now look at the implant site, quite established at 6 months post-implantation, you can see that the area is now quiet. There's really minimal or no residual hyperemia. And again, no conjunctival retraction, favorable position of the conjunctival flap, and again, no staining on fluorescein, indicating that the area is healthy and no sign of erosion.

And just an alternative view. This is looking in through the pupil with the indirect ophthalmoscope. You can see the implant sited in the vitreous cavity. And with transillumination, you can see the red glow coming back through the center of the implant.

So just some practical aspects that I'd like to expand on, in terms of monitoring. Although monthly reviews have been mandated by the VELODROME trial, these could potentially be extended, in terms of disease activity monitoring, to some degree. But as I see it, regular clinic checks will be necessary to monitor for conjunctival integrity as the months go forward, because early signs of erosion or retraction can sometimes be identifiable at the slit lamp, but asymptomatic for the patient. And of course, should these complications occur, it would be very important to identify and treat these, perhaps with topical lubricants, or topical steroids, to reduce the risk of endophthalmitis going forward. And after every implant refill, it's very important to its inspect internally for any signs of septum dislocation with the indirect ophthalmoscope.

In terms of patient satisfaction, this was reportedly very high in the Archway trial. And I've already mentioned, that in my small patient group, my patients seem to be very, very happy with every aspect of the device. The efficacy, the comfort, even the surgical technique. It was all tolerated very, very well. And they appreciate the hugely useful potential reduction in treatment burden that this may offer, for both the patients and the carers.

So in terms of my thoughts on the role of the device for the UK AMD population, the Ladder and Archway studies demonstrated with the 100 mg/ml dose, the dose that is now in commercial use in the United States and used in the VELODROME trial; the vast majority of patients did not require a refill until 6, 9 or even 12 months, and maintained sustained vision, good vision, up to 96 weeks. And this echoes my experience with my small group of patients: in my 4 patients, their disease has remained absolutely inactive, through to the 6 to 8-month time point. So I personally, am optimistic that we do have a new and useful treatment modality for this group of patients.

As I've mentioned, in terms of tolerability, the surgery and the refills have been well tolerated by my patients so far. In terms of safety, I still have concerns about the conjunctival issues that have been raised, and they remain at the forefront of my mind. And it's for this reason that my surgical approach is fastidious at the time of implantation. And also, very careful monitoring of the implant site at each visit, so that I can mitigate or manage any complications. The standards of surgical implantation, as I have mentioned, are really crucial for the safe delivery of this device.

So thank you for your attention. Please now watch the next segment with Doctors Holekamp and Brown.

<< SEGMENT 4 >>

David Brown, MD: Thank you. This is David Brown, Retina Consultants of Houston. We're going to show "Experiences from the USA." I'm pleased to have my co-faculty with me, Nancy Holekamp from St. Louis, Missouri. Nancy's going to show us a case with the port delivery system. Nancy?

Nancy Holekamp, MD: Thanks, Dave. Yes. I would like to start things off by sharing with you the very first case of the PDS or port delivery system that I ever had. This is a patient I enrolled in the Archway clinical trial. In January 2019, her right eye developed wet AMD, and at that time, she was already getting injections, anti-VEGF injections in the left eye. I entered the right eye into the Archway clinical trial and I continued anti-VEGF injections in the left eye with ranibizumab.

And what I'm going to show you right now is a clip of a surgery like this patient had for implantation of the PDS. What we see here is a cut down in the sclera with a sharp microvitreoretinal (MVR) blade and then laser ablation of the pars plana to minimize the risk of vitreous hemorrhage. Then we see a super sharp blade going straight in and out, and then implantation of the port delivery system. It's designed so it is self retaining at the sclera without any sutures. The final step would be to cover that implant with conjunctiva and Tenon's; it's a double layer closure.

And after the surgery, after complete healing, which can take anywhere from 4 to 12 weeks, the implant resides at the pars plana, through the sclera, under conjunctiva and Tenon's and looks pretty good. It's hidden under the upper lid of a patient. They don't see it. They don't feel it. When the patient looks superotemporally, you can see the implant. You see the tip of it, which is the release control element that allows for the drug delivery, and in primary gaze, you don't see the implant at all.

This was the very first patient that I put into the Archway clinical trial and 3 years later, vision is 20/25 in both eyes. You can see that we got to the same clinical endpoint in 2 different ways. In the right eye, she had the surgery with the port delivery system with 5 in-office refill exchange procedures, and the left eye had a total of 55 anti-VEGF injections, but both eyes are doing well. What you'll see is that the PDS is a choice that patients can make for how to manage their wet macular degeneration. But just one more follow-up slide. The right eye, you can see the one with the PDS is completely dry and the left eye, getting the monthly Ranibizumab injections, still has persistent subretinal and intraretinal fluid.

And so we hypothesize that there may be some benefits to continuous drug delivery as opposed to the pulsatile delivery that we get with injections. But I think this case is a good example of the choice that we're now able to offer our patients. This choice actually does come with a higher risk profile, and one of the biggest learning points in the PDS is incision size. And I was going to pass the discussion over to Dave here because I think he has a case that illustrates this. Dave?

Dr Brown: Yes, Nancy, Thank you very much. I can say that these patients are subjects -- and most of them are in the trials, some of them are outside that have been done commercially -- are some of the happiest patients I have. They really like them. The ones that don't have problems really like it. However, as in any surgical procedure, you can have problems. When we started the initial phase 2 studies, the initial recommendation was an incision between 3.5 mm and 3.7 mm. Because one of the complications early was vitreous hemorrhage, before we did the meticulous laser that Nancy showed, I and others were concerned that maybe it was because the incision size was too small, so I really pushed all my incisions to that 3.7 millimeter. This is a surgical case where you can see I've gone to 3.7 millimeters.

I'm enlarging right at 3.7, case goes well, but then as you'll see on refilling 6 months later, my partner has to use quite a bit of force and the implant dislodges into the vitreous. This case turned out okay. Another one of my partners, Charlie Wykoff, removed it surgically and the patient's gone on about his way. But now, my teaching point is we've changed the incision size to less than 3.5 mm and I try to make it as small as possible so that the implant fits in. My implants now are very, very snug after this and we haven't had another dislodgement. Nancy, what do you look at on your incision size?

Dr Holekamp: I agree a hundred percent, Dave. I try to make it up to 3.5 millimeters long, but certainly not any longer than that, and I think a snug fit is a better fit because it's a self-retaining device based on the design of this drug delivery implant.

Dave, I think a really key part of this is the refill-exchange procedure, to do it with the least amount of trauma or pressure, and it really takes some practice to identify that central septum, which is only about a millimeter in diameter, and to cannulate it in a perpendicular fashion with the refill exchange needle because we know we're exchanging the full volume of this drug delivery implant with new drug at every refill exchange procedure. What are your tips for an atraumatic refill-exchange?

Dr Brown: Like any surgical procedure, I think the first step is knowing the anatomy. Here you really need to know the anatomy of the device and what you're looking at. Here's a beautiful diagram of the parts of the port delivery system. There's a silicone cover and then a septum, and that septum has actually got some thickness to it, but the very center part of that septum is where you need to go through perpendicularly. You want to make sure that you're sterile, but I think the biggest thing is visualization. I wear loupes, task lighting's great. I think the best would probably be the headlamps like the vascular surgeons will use so your light is exactly where your loupe is. Again, the septum is incredibly important. Currently, the device is on a temporary hold because of dislodgement of the septum. I wanted to show you what that looks like. Unfortunately, we've seen that here in Houston.

The next slide I'm showing you is just what it looks like in an uncomplicated refill. The septum is that little white circle you see that I have pointed out in the middle of the darker area. You can see the flange around that, and in a normal implant or uncomplicated refill, when you look in the eye tangentially, you can see the clear PDS. This is what it looks like if there's septum dislodgement. There's darkness, there's no center, white septum can be seen, and then when you look at the implant itself, you can actually see that septum dislodged into the bottom.

It's obvious once you've seen it or know what to look for. We found that the easiest way to visualize the septum is to put your slit lamp beam right to the side of it, so indirect illumination. This is also the best way to take a slit lamp photo of it.

Dr Holekamp: So Dave, I'd like to just chime in here that I describe septum dislodgement to my patients as having a bottle of wine and the cork goes all the way in the bottle, and at that point, you can't perform any additional refill exchange procedures and the device really isn't working anymore. An option for these patients is either to have another PDS or to go back to having injections, but I think it's important to mention that at the timing of this recording, the PDS is on a temporary voluntary recall. So I think everyone should stay tuned.

Dr Brown: We're talking about surgical retinal procedures: we've got some other cool surgeries we're doing, both Nancy and some other of our colleagues around the country. I'm going to show you 1 video of intra-transvitreal subretinal delivery but here you see just that 34 gauge cannula going subretinal with a very controlled bleb. We've used this for both cell delivery and transgene delivery. Nancy, why don't you show another cool procedure that was done in some of our gene therapy trials?

Dr Holekamp: There's a gene therapy technique where a catheter is put into the suprachoroidal space and it delivers subretinal gene therapy. This is a video showing this catheter being looped into the suprachoroidal space. It stretches back into the posterior fundus, then a needle comes out, perforates the retinal pigment epithelium (RPE)-Bruch's membrane and creates a bleb in this subretinal space, and you can see that there's a cartoon on the left displaying this, but an actual surgery on the right, which is courtesy of Jeff Heier at Ophthalmic Consultants of Boston. This is another surgical approach that is being explored for gene delivery into the subretinal space. More to come on that. I think it's been tested in early phase one clinical trials so far.

Dr Brown: Thanks, Nancy. Great case and it's been a great discussion.

Dr Holekamp: Well thank you for your attention and please watch the next segment where we will talk about patient monitoring with surgical approaches.

<< SEGMENT 5 >>

Dr Brown: Thanks again. I'm David Brown, a retina specialist from Houston, Texas, with Nancy Holekamp, my colleague from St. Louis, Missouri. In this segment, we're going to discuss patient monitoring when using the surgical procedures to treat neovascular AMD. Nancy, why don't you tell us how you talk to the patients who are considering a port delivery system.

Dr Holekamp: Well, Dave, I have a lot of patients who are very interested in the PDS, and mostly it's patients who have a high treatment burden and really have a lot of anxiety and fear surrounding these injections. So number 1 is patient selection, people who you think might really be attracted by the PDS because they won't need injections anymore. So what I tell them is that it's a surgical procedure and therefore it has a risk profile that's similar to any surgical procedure. So the risks are, of course, bleeding or infection. And we know from the Archway clinical trial that the rate of vitreous hemorrhage was less than 5% once laser to the pars plana was introduced as a very important and key step in the surgical procedure.

We also know that the rate of endophthalmitis was 2 to 3 times higher than we have for intravitreal injections. Now, that rate of endophthalmitis was related to steps in the surgical procedure and there have been updates to the instruction for use. So now it's very important to cover this implant with both conjunctiva and the Tenon's layer. But nevertheless, you have to have a very frank conversation that there's a value proposition here where you may accept a slightly higher risk because it's a surgical procedure, but you would have the benefits of fewer injections. And that's true for the majority of patients with the PDS. So very, very important to discuss the risks, benefits, and alternatives just as we would for any surgical procedure.

So that's kind of what I discuss with patients beforehand. And they self select. This is an attractive option, as I said, for some patients. But after the implant, it's very important to set the expectation that because it's a surgical procedure, there will be an expected temporary decline in vision. As they heal, their eye is red, there are stitches on the surface of the eye that need time to dissolve. They will be taking drops for about a month to a month and a half. It's just important to lay the groundwork so that you're managing the expectations with this device.

Dave, I think it's also very important to talk to patients about what that refill exchange procedure is like, particularly that it's done in the office and not the operating room. Maybe you can tell us what you tell them about a refill exchange procedure.

Dr Brown: Yeah, most of these patients have had injections before, and so I tell them a couple things. One, they don't feel it as much. You don't have any sensation of going through the choroid. And so they like that. The one thing they do need to know is there is often pressure on the eye. And while some of my uncomplicated refill techniques are 15 to 30 seconds, some of the tougher ones are 5 minutes or more. So you need to tell them it can be longer, hang in there with me. But they're getting it way less frequently and really haven't had patients have trouble themselves with the refill technique. It's really been the surgeons figuring out the technique and difficulty going through those septums with more fibrosis over the top.

Speaking of refill technique, how do you know when to do it? Nancy, do you recommend every 6 months, like was in the trial? Or do you watch them closely? How do you monitor them? Give us what your current thoughts are.

Dr Holekamp: Well, Dave, in the US we've had the PDS FDA approved for about a year. I started putting them in my clinic patients in early 2022, and so most of them have reached the point where a refill is recommended. So right now, I am doing the refill exchange procedure every 6 months, as recommended by the Archway clinical trial, because I know that 95% of patients won't need supplemental injections if they get the refills. And so patients are very happy to come in, get the refill, and then go on their merry way. But the real question is, what about monitoring these patients? Archway doesn't tell us much about monitoring because in a clinical trial, everyone has to come back monthly. So what I'm really struggling with is how often do I have to see them between these 6-month refill exchange procedures? I think it depends on their fellow eye and what the risk for exudative disease is in the fellow eye. We now know that there can be complications with conjunctival retraction or erosion that expose the implant. So right now, Dave, I'm figuring out the monitoring. What's your approach?

Dr Brown: Typically, they have a fellow eye, so I'm seeing those eyes every 3 months anyway. I think as you push past 6 months, it's very reasonable to either bring them in for an optical coherence tomography (OCT), have their local eyecare provider, ophthalmologist, optometrist, if they're close, doing that OCT, or consideration of home monitoring. I know you've got a lot of experience in this. What are your thoughts?

Dr Holekamp: Well, I think home monitoring with something like the home OCT is going to be very valuable for these PDS patients where they can just monitor themselves at home. But of course, that's not ready for primetime yet. It's only been studied in clinical trials. But I think the future looks bright for home monitoring for our patients who have these extended more durable treatments.

Dr Brown: Well, thanks for your attention. I think we've got a lot to learn as we continue on. And please watch the final segment with our colleague, Dr Claire Bailey.

<< SEGMENT 6 >>

Dr Bailey: Hello, I'm Clare Bailey, a consultant ophthalmologist and lead of clinical research at Bristol Eye Hospital in the UK. Welcome to the concluding segment for this activity.

We've just heard from 4 really great speakers and experienced retinal surgeons. Some take-home messages are: the management of neovascular AMD is a very active area of clinical research, and there is a strong desire from both patients and clinicians to find longer-acting solutions; there is good evidence for the use of a PDS with a long duration of action before refill and high patient satisfaction, with over 88% of patients in the study stating that they preferred the PDS to their previous intravitreal injections; the PDS requires a careful surgical approach with correct management of the incision site, including cautery to the choroid, which has reduced the risk of vitreous hemorrhage occurring during the procedure; the importance of securely covering the implant with both Tenon's and conjunctiva has been emphasized to try and avoid conjunctival retraction, which, if present, may increase the risk of endophthalmitis; careful attention to technique is also required for the refilling of the PDS; and finally, patient education is very important so that they fully understand the different options available to them, including research possibilities.

It just remains for me to thank our excellent faculty, Laura Sararols Ramsay, Ramsey, Roxane Hillier, Nancy Holekamp, and David Brown for their excellent talks. And thank you for your attention. Please continue to answer the questions and complete the evaluation.

This transcript has been edited for style and clarity.

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