Rishi P. Singh, MD

A panel of ophthalmologists discuss strategies for managing AMD and DME patients who exhibit suboptimal responses to their current anti-VEGF therapy.

Addressing Suboptimal Anti-VEGF Response in Neovascular AMD and DME

1:00 Suboptimal Response
6:30 Treatment Strategy
11:10 Response to New Therapies
14:00 Imaging for Monitoring
18:30 Role of Ang-2

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Addressing Suboptimal Anti-VEGF Response in Neovascular AMD and Diabetic Macular Edema

To watch the video series component of this episode, click here. 

1:12 Suboptimal Response
6:42 Treatment Strategy
11:22 Response to New Therapies
14:12 Imaging for Monitoring
18:42 Role of Ang-2

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Recent advancements in the management of lung cancer brain metastases have significantly improved patient outcomes. The integration of novel therapies, including targeted treatments and immunotherapy, has shown promise in enhancing response rates and prolonging survival. Imaging techniques play a crucial role in monitoring treatment efficacy and disease progression. Angiopoietin-2 (Ang-2) has emerged as a potential biomarker for assessing treatment response and guiding therapeutic decisions. These developments underscore the importance of a multidisciplinary approach in optimizing treatment strategies and improving the quality of life for patients with brain metastases from lung cancer.

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.

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.

Rishi P. Singh, MD

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