Optimizing Anti-VEGF Treatment Outcomes in Neovascular AMD and DME - Episode 5

Treat and Extend Strategy for Anti-VEGF Injections

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Experts offer their clinical experience and advice for applying a treat and extend strategy with anti-vascular endothelial growth factor (Anti-VEGF) injections.


Ehsan Rahimy, MD: Monthly anti-VEGF injections can have significant treatment burden. We’ve touched on that here already. How do you employ treatment addiction strategy in your practice with your patients?

Jonathan Jonisch, MD: Taking it from the beginning, when we started using these drugs, we were giving patients monthly injections. That was on label; that’s how the clinical trials were designed. Then we quickly realized that very few [patients] need injections with the original medications that frequently. The community started developing other algorithms to try to reduce treatment burden and visit burden.

There was PRN [as-needed treatment]. The patients were still coming in monthly and not getting treatment every time. It was a zigzag, and the patients had anxiety about coming to the office not knowing whether they were going to get the [injections]. Our staff was burdened with getting authorizations for drugs and patients not receiving the drug. The majority, probably over 90% of us in the United States, are treating and extending, meaning the patients are getting the [injection] each time they come and we’re trying to extend the interval. So we’re trying to get to that magic moment where they’re coming in to see us as [few times] as possible, getting the least amount of injections as possible, while still maintaining the maximal vision gains and maximal efficacy.

The bottom line is there [are] no level 1 data to tell us what is the best treat-and-extend algorithm. And the detriment of that is the manufacturers of the drugs in their clinical trials have different mechanisms of trying to recreate a treat-and-extend program. That has led us to have a difficult time comparing newer drugs that come to the market and trying to predict their efficacy. So I think most of us employ a similar treat-and-extend strategy. Obviously, it’s almost all based on OCT [optical coherence tomography]. Most of us tolerate some fluid in certain cases in AMD [age-related macular degeneration] with subretinal fluid, but for the most part, we’re all trying to treat to a dry retina in most of these diseases. We all know our own algorithm, but it’s difficult to write it down and recreate to make it uniform in a clinical trial.

Ehsan Rahimy, MD: Where are most of you capping your extensions at this point? I imagine we’re all treat-and-extenders. Anybody becoming a little bit more flexible with patients, either the longer we get into this game or because coming out of [the] COVID-19 [pandemic]…has been forcing us to reconsider how long patients want to go?

Ali Khan, MD, FACS, FASRS: I typically go to 16 weeks. It’s the longest that I’ll go, and then [I’ll] have a discussion about [whether] we switch to a PRN approach at that stage. But depending on the disease and how bad [it was] at [initial] presentation, I usually start extending by 1 to 2 weeks between visits. I don’t go much longer than that, but I’ll go up to 16 weeks. That’s my mental cutoff. If they’re good at 16 weeks, that’s when the PRN approach and discussion seem to make sense to me. That’s how I do it.

Veeral Sheth, MD, MBA, FASRS, FACS: Sixteen weeks is my cap as well. You’re right; COVID-19 pushed us on that a little. We all saw patients come back after a significantly longer period, and they were fine. So maybe it has us thinking, “Can we go longer with these patients?” I’m still hesitant to go to PRN, because you do it a couple of times and [see] subretinal hemorrhages come back, and those are catastrophic cases. So I have a conversation with patients who are at 16 weeks for a couple of cycles, and I say, “We can use this option, but to be very clear, I’m not saying you’re not coming back.” I see them more often then. So I let them make the trade-off. Do they want to come in more often with potentially [fewer] injections, or do they want to come in 3 to 4 times a year and get the injections automatically?

Jonathan Jonisch, MD: I traditionally extend to 12 weeks. [As] Ali and Veeral have said, I have extended a bunch of patients to 16 weeks knowing that for a lot of these patients, there’s no significant drug in the eye between that 12- and 16-week time frame. But there’s also not a lot of VEGF being elevated in that short span when there’s not a lot of anti-VEGF on board. By the time we see them at 16 weeks, we’re knocking down the VEGF that’s being produced in the eye theoretically.

We don’t know. Every eye is different. Not every eye has the same VEGF load, VEGF production, VEGF clearance. So we’re averaging this. And to the point, do you switch to PRN? We know that these drugs are great at getting rid of the disease, and they’re also good drugs for keeping the disease from coming back. So there is a trade-off. We know that [if] you stop treating the patients [with] wet AMD, [results from] different studies may say one-quarter, some may say one-third, over the next couple of years are going to recur. And some of those may have permanent vision loss. So you have that conversation with the patient. Some of them are willing to take that risk. Some would rather get 3 injections a year if they’re [experiencing stability]. But how to exit anti-VEGF [therapy] is uncharted territory in our field.

Transcript edited for clarity.