The relationship between outer retinal integrity, subretinal fluid may affect treatment outcomes

Video transcript

David Hutton [DH]: I'm David Hutton of Ophthalmology Times. The American Society of Retina Specialists is holding its annual meeting this year in New York. At that meeting, Dr. Justis Ehlers is presenting, “Higher order OCT feature assessments of the impact of fluid dynamics on visual acuity in neovascular AMD in a Phase 3 clinical trial: The importance of outer retinal integrity.” Dr. Ehlers, thank you so much for joining us today to discuss what is certainly a keen topic of interest for those treating these patients. Tell us about your presentation.

Justis Ehlers, MD [JE]: Thanks so much for the introduction, David, it's really tremendously exciting to be able to present this data. One of the key interests as retina specialist for us has been how to manage fluid and what that impact is for our patients.

There's been a lot of debate around the positive potential impact of subretinal fluid, and one of the things that we're learning is our abilities now to better measure features within the retina. And so for this analysis, what we did is we took the Phase 3 HAWK clinical trial, and we looked at this in a treatment agnostic standpoint, and evaluated visual acuity in the context of not only fluid, but also fluid volatility, as well as outer retinal integrity.

So we looked at whether or not there was underlying atrophy and what the quantitative ellipsoids zone integrity were in these eyes.

One of the interesting things is that with wet AMD, obviously, it's an outer retinal problem. And so there may be pre-existing atrophy and damage that exists at baseline. And those patients even when fluid goes away, they may not be able to improve.

Up until now, there haven't been great ways to measure this to better understand what dry meant: There may be dry with atrophy and dry without atrophy. And so using this technology, we were able to differentiate between eyes based on ellipsoid zone integrity. So those eyes that had preserved outer retinal structure, those that didn't, but then to specifically look at compartments of fluid being there or not being there.

What we found was interesting: In the eyes that had the best visual acuity were those eyes that were completely dry and had a preserved outer retina. Those eyes that had among the worst visual acuity were those eyes that had were dry and had no outer retinal preservation. So they had on underlying atrophy that was either pre-existing or over time developed based on progression of their disease.

I think this has important clinical implications, because we need to understand what's going on in terms of the overall retinal integrity and how aggressively we should treat fluid. We did find that subretinal fluid being present, was in the second highest visual acuity group. But what was also important was that we found was that if there was highly dynamic subretinal fluid, so that meant that if that fluid was volatile from visit to visit, those eyes dropped significantly in terms of their visual acuity over time. So as we look at fluid, I think, you know, what we take away is that not all fluid is created equal. If that fluid is dynamic and not static, we may really need to consider being more aggressive in terms of the way that we treat it. And understanding that patient and how they're responding to therapy, I think is really important. And it's changed for me how frequently I may image a patient and how I look at how aggressively I may want to extend a patient or be more conservative in that in that regard.

DH: What's the next step for this research?

JE: Well, I think we want to continue to validate this. Multiple studies have shown that volatility of central subfield thickness is associated with poor visual acuity outcomes, and we're now better able to understand the anatomical sequelae that probably lead to those poor functional outcomes. We're going to look at this more in terms of better understanding of how we can see this in our aggressiveness of treatment and want to confirm this with additional studies, you know, going forward.

DH: Great, thank you so much for joining us today. We appreciate it.

JE: Absolutely. Thanks so much for the invitation, David.

Note: This transcript has been lightly edited for clarity.