Optimizing Anti-VEGF Treatment Outcomes in Neovascular AMD and DME - Episode 7

Significance of SRF vs IRF in nAMD

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Experts discuss the management of subretinal fluid (SRF) and intraretinal fluid (IRF) in patients with neovascular age-related macular degeneration (nAMD).


Ehsan Rahimy, MD: Ali, fluid in the retina has been thought to lead to deleterious visual outcomes over time in neovascular AMD [age-related macular degeneration]. What’s the clinical significance of where the fluid is located? We’ve seen a lot discussed about intraretinal vs subretinal fluid. What can you tell us?

Ali Khan, MD, FACS, FASRS: This is a topic that’s been discussed for a while, even when we were in fellowship, and it’s still going on. There’s a lot of post hoc analyses of the registration trials for aflibercept and others that looked at imaging correlates to visual outcomes. And those post hoc analyses showed that intraretinal fluid seemed to be more related to poor vision outcomes compared [with] subretinal fluid alone.

There’s a study…called the FLUID study where they compared patients with neovascular AMD treated with ranibizumab and divided them into 2 groups. One group [was] where you were intolerant of any fluid, meaning you treated to a completely dry macula. [They] then compare that [with] a subretinal fluid–tolerant group, where as long as it was subretinal fluid, you can leave it there and still extend on a treat-and-extend approach. And [results from] that study showed that the visual outcomes were similar, with fewer injections in the subretinal fluid–tolerant arm.

Most of us would agree that some subretinal fluid isolated in a patient [with] neovascular AMD we may tolerate. We’re not necessarily trying to get subretinal fluid, meaning we’re not extending our intervals to try to promote subretinal fluid, but if there’s a little and their vision and OCT [optical coherence tomography] [result] is stable, I’m fine leaving it and perhaps extending to see whether that fluid remains stable. [David Sarraf, MD, at UCLA] and others have tried to figure out whether this is truly exudative subretinal fluid or…more transudative subretinal fluid. That’s above my patient interaction level, where I’m not going to go into that much detail with them, but [if there is] a little bit of fluid and vision’s good, they’re usually OK with leaving it.

Ehsan Rahimy, MD: Along those lines, much has been made of some cases of subretinal fluid being allegedly protective. Do you subscribe to this? Do you discuss that with patients? What are your feelings about that?

Jonathan Jonisch, MD: It’s a lesson in following data. If you polled the retina specialists 10 years ago, 15 years ago, when we were treating [as needed], beginning to treat and extend, no one would have thought that patients with residual subretinal fluid were going to see better than patients who had no subretinal fluid after the first couple of injections. We weren’t talking about that. [Now] you see these data signals pop up, and at this point, most of us know it’s real. There are patients who see better when they have this.

To take a step further and say whether it’s protective…there are some patients who have a little bit of subretinal fluid. And then you dry it up, and we’ve seen them lose vision. It’s almost a nomenclature thing. Are you going to [say] that it was protective or that [it] was just the disease progression? But there are some patients [for whom] when you dry [up the subretinal fluid], they develop a little atrophy. So it’s tough to say whether that was protective, but semantics may lend [themselves] to that.

Veeral Sheth, MD, MBA, FASRS, FACS: John, when you mentioned that, you said some patients. The difficulty is it’s hard to predict which patients these are. We all have patients where there’s some subretinal fluid. You dry [it] up, you get a little more aggressive with the treatment, and they do better. So it’s hard to predict which of these patients [it’s] going to be. I have some patients, and which ones am I tolerant on? It’s just patients [with] chronic [disease who are] seeing well enough, and I’m convinced. It’s not a huge group of my patients, because I tend to want to dry [their subretinal fluid] for the most part, because on average it is better for the patients. But there are some [patients] where you just know and you try to get more aggressive. There’s no impact on their vision, you back off, there’s no impact on their vision. [For] those patients, I’m OK saying I’ll allow a little bit of fluid. Because there’s some [for whom] you could treat them every 2 weeks, and then you’re seeing the result you want, but it’s not sustainable. So it’s a very specific set of patients for me.

Jonathan Jonisch, MD: And I think the corollary to that is, what is the fluid doing? If every time you back off, the fluid’s increasing, it’s called the dynamic fluid. That worries us. But when you start treatment, you get reduction of subretinal fluid. There’s some residual fluid, and then no matter what you do, that just doesn’t move. You start extending and it’s not increasing; it’s not dynamic. Those are the patients I’m feeling more comfortable extending [treatment for], and I haven’t seen bad effects of extending [treatment for] those patients.

Ehsan Rahimy, MD: John, that’s a great point. I like the idea of dynamic fluid, because it’s not just a fluid, at least [for] a lot of these types of patients. They often have a concurrent PED [pigment epithelial detachment], and you can see fluctuations in the height of the PED along with the fluid as well. It tells you that there’s a dynamic process, and I’m careful in terms of how much I back off.

Transcript edited for clarity.