Optimizing Anti-VEGF Treatment Outcomes in Neovascular AMD and DME - Episode 9

Managing Suboptimal Responders to Anti-VEGF Treatment

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Experts discuss how they define suboptimal responders to anti-vascular endothelial growth factor (Anti-VEGF) treatment and how they manage the care of those patients.


Ehsan Rahimy, MD: It’s a great point. It’s a good segue to ask this. The last thing we want is to introduce a problem. Maybe somebody’s a suboptimal responder, but we don’t want to cause problems. So what are some tips for you guys? How do you have this conversation? How do you bring it up to patients if you’re already thinking you may want to potentially introduce one of these newer medications?

Jonathan Jonisch, MD: I think the beginning part of your question kind of referred to the nonresponders, and that’s kind of a whole conversation. I think each of us may define what’s a nonresponder slightly different. I think it’s one of those [cases where] we all know it when we see it. You have patients with really high disease loads that require really frequent anti-VEGF and they’re not able to be extended. They may have good vision, [or they] may have poor vision. I think a lot of those [patients] we refer to as suboptimal responders because they can’t really be advanced.

Then we have patients that we are able to advance but they lost vision. I don’t think that’s an optimal response, but their treatment burden may be able to be controlled really well and be extended. From that point, you can make the argument that [the] drug did everything it could, [but] the disease didn’t allow the patient to gain as much vision.

We are having more options now of where to switch patients when [that happens]. We can have a conversation about switching from one anti-VEGF monotherapy to another. We’ve all seen some patients respond better to one or the other. We now have a dual mechanism anti-VEGF that targets angiopoietin 2, [which is] possibly being a driver of some of these diseases. Some patients are benefiting from switching over to that.

In the future, we’ll have some higher dose treatment. Some patients may require higher doses to either get more efficacy or possibly just some durability. And then in the future, I think between gene therapy and possibly targeting some other isoforms of VEGF we may be able to improve efficacy and treat some of these nonresponders. So it’s different, we have corticosteroids in our diabetics as well. Those remain relevant in the nonresponders.

Veeral Sheth, MD, MBA, FASRS, FACS: Yeah. I would say my definition of nonresponders or suboptimal responders has probably changed over time. I think before it was probably just patients that didn’t dry well, but now it’s patients that don’t dry well, or that I can’t extend out. So I think we’ve answered the first part of question. The second part was, how do you approach that patient? What do you talk to them about? And I think I would kind of fall back to the comments we made earlier about feedback. They can see their OCT [optical coherence tomography]. They can see [they have] some red on that scan, or we’re not able to get past a certain amount of time. And then I tell them there’s a chance [of improvement] if we switch you to a new medicine.

I think [with] every generation of new medicines that comes out we have a wave of these conversations. I think you have that conversation and it’s easy for patients to understand [because] you’ve built that trust over time with them, too. And going back to something you mentioned, Ehsan, [there is] a hope. [If a patient has] been using this for a long time, let’s switch to something else. So there’s a lot of factors that play into that conversation.

Ali Khan, MD, FACS, FASRS: Yeah. I do think there’s 2 different groups. There’s the patients who have persistent excitation regardless of the drug, and then there are those that you’re just thinking increased durability. I think the conversation is different for those 2. I’ve had patients very stable on 1 drug but can’t get past 6 weeks. I will have a discussion, “Hey, your drug’s working, but if we try this other one, there’s a chance that you could go longer,” and I think patients are on board.

It's a little easier to sell when you show them their OCT and there’s still fluid then say, “Hey, this one medication it’s working but not well enough, we’ve got to try another one.” I think people are also willing to do that switch. Again, that’s in a setting of having primarily 3 to 4 drugs total. I think that everyone’s going to have to pick and choose what they decide to switch to, that’s a separate question. But again, kind of to Veeral’s point, I think there’s 2 separate populations and you may end up switching back and forth a little bit differently between the 2 types of patients depending on how they’re progressing.

Ehsan Rahimy, MD: I really liked what Veeral said, too, in terms of how your own definition of what a suboptimal responder is changes over time. Initially, if you asked me, it was based on a lot of objective criteria like we talked about, but over time, more and more of that pie is occupied by the subjective feelings of the patient. They can be doing great at 4 weeks, 6 weeks, 8 weeks, 10 weeks, [but] that patient could be miserable, and they want anything to extend out their treatment interval. Conversely, I could have a patient with persistent excitation but well controlled disease and stable vision who otherwise that has to come every 4 weeks. I’m thinking in my head I’ve got to get this patient out longer.

Now, some of these patients are retired, live down the street, and they love coming into the clinic every 4 weeks. It’s not a problem at all for them. I’m sure we all have those type of patients too. So I’ve just been impressed to see how my definition of suboptimal response has definitely changed and it’s a lot more subjective than I originally thought. I don’t know if you guys feel the same way.

Jonathan Jonisch, MD: I think all of us would define an optimal responder kind of similar, right? Our optimal responders are like patients that dried out really rapidly, had a big gain in vision or maintained really good vision that they came in with. We were able to extend out [treatment]. They passed every test. These are like the A students. Every test we give them, every chance they have to extend, they pass with flying colors. They’re out 3 or 4 months. They’re happy. They’re seeing well. Everything beneath that, you can make an argument is a suboptimal responder.

Ehsan Rahimy, MD: Great point.

Transcript edited for clarity.