Ali Khan, MD, FACS, FASRS

Retina specialists discuss treatment and adherence strategies for patients with nAMD and DME. future

Promoting Treatment Adherence in nAMD and DME

 Through this discussion today, we haven’t talked about treatment adherence. This can be a significant challenge. We know from [results of] many studies [that] 50% of patients discontinue anti-VEGF therapy within the first 3 years. [Findings from] some studies have said within the first year, 30% to 40% of patients may discontinue therapy depending on the practice environment. And we know that adherence is an issue. First, I’d like to hear your strategy on keeping patients adherent to therapy. And with the change in this durability, do you think adherence would change as well and potentially improve?

[Diabetes] and neovascular AMD [age-related macular degeneration] are slightly different because the adherence for treatment with [patients with diabetes] has traditionally been worse, likely because these patients are more active, they’re working, it’s harder for them to take off work. But for both populations, AMD and DME [diabetic macular edema], having the patients understand what is happening and why they’re coming is big for me. Showing them their OCT [optical coherence tomography] [scans] and telling them, “These are what I’m looking at; these are the findings that I see improving” and explain[ing] to them why we’re changing things, whether in terms of the number of weeks or the drug, [so that] they’re being brought in and not being passive in the process has been the most successful for me.

And [to] the second part of your question about [whether] extended intervals improve adherence, in some ways, yes, [it’s] fewer visits, [it’s] easier for people to take off time and have it [be] more predictable. Once every 4 months [is something] people can plan for. Once every 6 weeks gets tough, depending on the type of job you’re in, and for caregivers, we need to bring [in] some of our older patients [with] neovascular AMD [nAMD]. So extended interval duration will help with adherence. On the flip side, I don’t want to go too long because sometimes if patients forget about “I have my eye doctor or my retina specialist appointment,” that can be a little bit of a drop-off. And when you’re at the end of an extended treatment interval, that’s when I’m worried that if they go maybe 2 or 3 weeks longer, I don’t want something terrible happening [such as] a hemorrhage. So finding a happy medium where they have an expected appointment once every 4 months, for example, [and] it might not go much longer than that, simply keep[s] them in the fold and keep[s] them in our scheduling processes.

 I agree. There are so many things we could do to improve adherence. We have to talk to them about missed appointments and getting back in right away, not wait until the next interval appointment, try to give them encouragement on the OCT [optical coherence tomography] [scans], [and] show them pictures…to say that they are getting better. I like to show them a graph of their OCT [scan]. They show them the central subfoveal thickness over time, which our software does very well, show them the benefits of their incredible adherence to therapy and what’s happening over time. Overall, we have to encourage this because we know there’s a huge dropout rate with these patients over time. Getting them to come back and keep their appointments in high fidelity is important for us to be able to do this in a good way. Let’s touch a little bit on future treatments. What excites you? What do you think is interesting? You know the space very well. Is there something that you look at and say, “That’s going to make our patients have a great durable option with [fewer] injections and potentially [fewer] complications”?

Much has been spoken about gene therapy options and how we deliver them surgically or in the office with suprachoroidal therapy. If we do have treatments that we can do in the office with every-4-months durability, that’s tough to beat. So the suprachoroidal delivery of gene therapy is interesting. That’s office based, which most people can get their head around, and doesn’t require going in the operating room, which has its own risks. If that can be delivered at scale with durability as good as our current drugs or perhaps longer, that has the potential to change my mind in terms of how I would approach treatment in these patients. So office-based [therapy] with extended durability is what could work at scale. And the suprachoroidal option is potentially promising. There are data being presented at our current meetings, and everyone will look forward to the full trial data for those delivery options. But gene therapy delivered in the office is another paradigm shift that can happen.

 I would agree with you. I would also add tyrosine kinases to the mix there. That’s been a burgeoning area of understanding of the new MOA [mechanisms of action] that tyrosine kinases can offer. And I agree with you on gene therapy; surgical delivery of this is probably impractical. And office-based delivery of gene therapy may be the best approach to suprachoroidal delivery platforms. Tyrosine kinases at least offer another ability, which is that they affect all isoforms of VEGF, not only VEGF-A but other isoforms of VEGF, including downstream effects of inhibiting ANG2. So it can have a synergistic effect alongside some of the other drugs that we’ve had in clinical practice so far.

 I agree. It’s going to be a busy few years with clinical trial results coming out but exciting nonetheless.

We have so much promise that’s happening and so many great opportunities in our field in the next few years. I want to thank you all for joining this 

Extending Treatment Intervals for Durable Therapies for Neovascular AMD and Diabetic Macular Edema

. Thank you again for watching, and thank you, Dr Khan, for participating.

Transcript is AI generated and edited for clarity and readability.

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Retina specialists discuss treatment and adherence strategies for patients with nAMD and DME. They also comment on the future of nAMD and DME management.

Selecting Therapies for Individual Patients With Neovascular AMD and DME

 When you talk about some of the therapies, and we have so many available now, we talk about off-label bevacizumab, we’ve got unlabeled drugs with anti-VEGF, we’ve got the combined bispecific, we’ve got combined, we’ve got high-dose aflibercept. How do you work your patients through these therapies and determine what the right option is based on their presenting findings or something else that you may consider?

That’s a great question, because if we’re looking at similar duration intervals, that is taken out of the equation of both drugs and achieves that 12- to 16-week interval in a large percentage of patients. That was the initial thing most patients would be interested in, [which] is how long you can go, but if you have 2 drugs that could do the same, it’s a little more of a discussion. So I bring up the fact that 1 molecule is inhibiting 2 different proteins. Some patients get into that aspect of type 2 inhibition, especially in the patients [with diabetes], because of the anatomic changes we saw in the [diabetes] faricimab trials showing some improved drying effect of the drug compared with aflibercept 2 mg. There is some anatomic consideration there that patients can understand. On the other side, if patients are already on aflibercept, many are comfortable with that drug. So the switch to the higher doses [is] conceptually very easy for them to understand while switching to a completely different drug; sometimes patients are a little hesitant or have more questions. So there’s a combination of things to consider, but particularly in patients [with diabetes] and patients with more of the anatomic findings on their OCT [optical coherence tomography] [scan] that I’m concerned with, that might push me toward including the type 2 inhibition with faricimab. However, both drugs, based on the durability, are going to be good options.

 I agree with you. The big driver for a lot of our decisions tends to be insurance first and foremost and then patient outlay of cost. And sometimes they will determine their therapies based on that. And for those who at least have that covered, then the more durable agents, and by that I mean the agents that are the newer agents, are the ones we try to migrate to over time because we know…how often we treat these patients, how much we get to give them medications, and how long we expect to treat them over time. It makes sense to pick the most durable agent possible for all these activities as well.

Dr Khan, one of the things [that] has been a controversy in our field has been loading doses. Many studies have used loading doses as part of the initial ramp-up, some as many as 5 or 6 in the diabetic macular edema [DME] studies and at least 3 or 4 in the neovascular AMD [age-related macular degeneration] trials. Talk to me a little about your approach and thoughts on loading doses.

The loading doses [for our prior agents] were easy to remember; it was always 3 monthly injections. With faricimab and the high-dose aflibercept, it’s been anywhere from 3 to 6, depending on the arm of the trial. For treatment-naive patients, I am following the loading-dose suggestions based on the trials. I’m still doing 3 to start, and if I’m seeing good effect, then I don’t necessarily continue beyond 3 loading doses and instead go immediately into the treat-and-extend [regimen]. [As] I said before, the trial’s treat-and-extend [regimen] started at 4-week intervals. I’m going [with] a little less than that initially, maybe at 2 weeks, in between the loading dose and the treat-and-extend [regimen] in a way if you consider the trial design. But for patients who are already on an agent, I have not reverted to a full loading-dose strategy. I’ve typically kept the patients at the same interval that they were on [with] the previous agent and adjusted from there, perhaps keeping them at that same interval for 2 to 3 injections, perhaps not extending immediately, but not going all the way back to a Q4 week loading-dose strategy. It’s that distinction between a treatment-naive [patient] and a patient [with] currently controlled or refractory [disease]. There’s a bit of a distinction there, at least in my practice.

I would agree with you. Most of us do loading without calling it loading; we treat till dry. And inevitably, we get anywhere from 3 to 4 to 5 injections in any way. But there’s been a lot of literature out there that show that loading doses matter in these patients because there is a disconnect between the OCT and vision. So giving the patients those 3 injections does make a difference in the final visual outcome in some of these patients over time. There is value in doing so. It simplifies the regimen, but we don’t tend to do them because we tend to follow the OCT, which is a reasonable parameter to follow and make sure we do that over time. So that’s another option to consider, [which] is treat till dry and then continue thereafter. You probably have the same effect [with] regard to loading overall.

Retina specialists discuss factors to consider when selecting a therapy for patients with neovascular AMD and DME as well as loading-dose recommendations for select patients.

Selecting Therapies for Individual Patients in nAMD and DME

Switching Patients From 2mg to 8mg Aflibercept for nAMD and DME Treatment

 Have you had experience with 8 mg of aflibercept to date? What has been your experience? Have you seen any differences as far as the 2 mg that you saw in the past?

It’s very early relative to faricimab because of the more recent approval. It’s a little different because people I’m using it [for], at least to start, are people who’ve been doing OK on our current of aflibercept dose of 2 mg and are trying to see whether we can go longer with the longer interval. So I am, similar to what you mentioned before with faricimab, starting to see some longer intervals in patients who are currently on anti-VEGF [therapy], but I haven’t had enough experience with treatment-naive patients or a significant number of patients [with] recalcitrant [disease] to see whether it’s making a difference in terms of real-world outcomes. But for patients who are already on aflibercept 2 mg, it’s an easy switch to consider simply because it’s the same molecule and the patients are comfortable with the drug that they’re on. So I’m interested to see what your and other people’s experience is [with] that switch, even with the same drugs [at] the higher dose.

 It’s early for these drugs. I don’t know whether I could make a comment about the efficacy of 8 mg thus far, but thus far we haven’t seen the safety concerns that we had in the past with other drugs, not anything in this realm but certainly with other drugs in the brolucizumab era and other drugs that were there. We don’t see that, which is very reassuring, but [in terms of] efficacy, we’re still waiting on new confidence over the next year or so for the data we’re seeing with our patients over time. For a patient who [has good control] in a regimen of 3 to 4 injections annually, what are your thoughts on transitioning them to these newer therapies?

To be perfectly honest, if somebody’s already on quarterly treatments or every 3 to 4 months, I’d probably [be] unlikely to switch those patients at this stage. [Because of] some of the things that you mentioned outside the clinical realm, including cost and considerations such as that, if they’re already on [treatment] every 12 to 16 weeks, I’m unlikely to rock the boat [for] those patients to get a little bit longer [benefit], partially because I still want to check on these patients…to make sure they’re doing OK overall, [that] there [are] no clinical examination findings that are concerning [or] changing. So those patients I’m more likely to keep [on treatment], but [for] treatment-naive [patients] and patients who have never achieved that 10-week interval, [I’m] more interested in seeing how that switch works out.

 I agree with you there. Those patients who’ve had quarterly injections, they’re on a good clip there. They may see an incremental benefit of just a few weeks. You’re having this other side of it, which [is that] you don’t want to extend [treatment] too far because you want to watch them. And these patients have fellow eye disease too; sometimes you have to watch their fellow eyes to see whether they [experience progression]. And that would be a good reason to bring them in earlier. But I agree with you. I’m transitioning those patients who are in the Q4 [or] Q6 category for aflibercept now to other drugs with a greater durability regimen because that would be helpful to understand better what the benefits may be of those drugs and those high-treatment populations.

Retina specialists comment on switching patients from 2 mg to 8 mg of aflibercept for the management of neovascular age-related macular degeneration and diabetic macular edema and transitioning a patient who has good control with aflibercept to a newer therapy.

Retina specialists highlight the safety data of both faricimab and high-dose aflibercept for use in treating nAMD and DME.

Safety of New Therapies in nAMD and DME

 Apart from extended durability, what else do you think that we need to achieve from these therapies to really be meaningful in regard to your practice and your patients?

I think safety is a big one. I think we’ve had experience with several recent drugs where safety concerns were brought up, perhaps after the clinical trials, and that I think is a big pause for most physicians, because the existing treatments we have are very safe in our hands. And I don’t think anyone wants the uncertainty or potential harmful effects of an unforeseen, perhaps inflammatory event that could cost a patient [their] vision. So I think safety after durability, of course, which is the primary end points in terms of these trials, there’s vision at a durable extended interval. But I think the safety concerns in the broader retina community are now paramount. That needs to be proven before I think people will truly adopt these drugs.

 Obviously, with any of these efficacy analyses, one of the other areas is potentially closure of the CNV [choroidal neovascularization] finally, or reduction of subretinal hyperreflective material, which we all think is the neovascular complex, which may benefit us to see that happen over time for sure from these drugs. And we talked about the safety profile of these drugs. Are there any new safety signals that were seen, any of these new drugs that have come out so far?

 Luckily, there wasn’t. So at least in the public trial data, there were similar rates of inflammation, which I think is the big one that most retina specialists are looking for nowadays between the comparator arms, which are aflibercept 2 mg every 8 weeks that had similar inflammatory events to the active arms of the trials, meaning the faricimab or the high-dose aflibercept. So hovering around 1% to 2% rates of inflammation and thromboembolic events, heart attack, stroke, no new safety signals in all of the trials. 

 I would agree with you that we’re so cautious right now [about] safety because we have what we’ve seen with brolucizumab in the past. Obviously, we’ve seen some events recently with the drugs and geographic atrophy, which has been concerning to us. Our heightened awareness is definitely there for these drugs. And so we’re really making sure that there are no safety signals. Thankfully, both of these drugs, both faricimab and high-dose aflibercept, have not shown any concern as far and they’ve been used in clinical practice.

Transcript is AI-generated and edited for clarity and readability.

Ali Khan, MD, FACS, FASRS

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