Dr. Ehlers: 
What biomarkers are there in neovascular AMD, besides for intraretinal fluid and subretinal fluid, that can help inform our treatment decision-making? This is CME on ReachMD. I’m Justis Ehlers, and I’m here today with Jennifer Lim. 
  
Dr. Lim: 
Thanks so much, Justis, for having me. When I see a patient with neovascular AMD, one of the things that I look for is the presence of a pigment epithelial detachment. And the reason for that is that we know that people with PEDs are harder to treat and they can potentially have worse visual outcomes. And, in fact, in the past it was thought that maybe you shouldn't use as strong an anti-VEGF drug to treat a PD for fear of RPE rips. However, in the literature that's come out, we've actually seen that the second-generation anti-VEGF drugs actually have better resolution of the pigment epithelial detachment. And so I frequently will use a stronger second-generation agent in the presence of a PED in order to get resolution of the CNVM associated with the PD and resolution,too, a pigment epithelial detachment.  
 
Dr. Ehlers: 
Yeah, Jenny, those are all really great points. For me, often some of the challenges is the decision around, do you treat and do you not? Is there CNV present, or is it an isolated PED? One of the other questions is, do we treat the sub-RPE fluid? Once the intraretinal fluid and subretinal fluid go away, how aggressive can we be? And for me, what I wondered, if I could share actually, three cases with sort of three different behavior types that all, at baseline, looked relatively similar. 
 
This first case here, the patient came in. Actually, pretty good vision, had clearly subretinal fluid here, as well as a relatively large pigment epithelial detachment. There wasn't much sub-RPE hyperreflective material in there. It looked predominantly serous. But because the patient was symptomatic, we were concerned about the potential for CNV and the associative subretinal fluid. 
 
But interestingly, there was no subretinal fluid at the edges. It was really just on the cap of that. We treated with anti-VEGF and the patient actually felt like they were getting better. We, interestingly, did not see resolution of the subretinal fluid, but slowly over time, the PED did resolve. We see still, here, persistent after 5 months, vision had improved to 20/20.  
 
When we look at the second example, here. This patient came in with 20/60 vision. We see overall, some evidence of some greater chronicity with some shadowing and pigment clumping on the top of the pigment epithelial detachment. Subretinal fluid, and a little bit of draping on the edges, there. This patient had felt like this has been there for a long time. This patient was treated with aflibercept, and after 4 treatments was pretty much identical.  
 
Did not want to continue treatment. We decided to just watch. And then, 10 months later, it continues to look identical and really, suggesting this is probably not a neovascular process, or at least one that doesn't seem to be responsive to anti-VEGF therapy.  
 
And then finally, we see another case. Again, when you look at the overall OCT signature of this PED, it looks very, very similar to the others. Possibly a little bit more of that sub-RPE hyperreflective material suggested of maybe some CNV complexes there. Importantly for me, I see that subretinal fluid not only at the cap of the PED, but also extending beyond it and beyond what I would say is just overall draping. And so, in this case, I'm particularly concerned around active CNV being present. 
 
This patient was treated with aflibercept and a very dramatic difference after a single injection. Actually, looked like what we see here at the month 6 image, with improvement in vision and much greater stability. So, again, when I'm thinking about can I treat the PED or not when I see this type of resolution, it certainly is a good goal to have in terms of overall disease stability. 
 
Dr. Lim:  
Those are beautiful cases, Justis. And we've seen in TENAYA and LUCERNE subanalyses that in eyes with choroidal neovascularization and PED that the second-generation agent faricimab as compared to aflibercept resulted in great reduction in the PED thickness during the head-to-head dosing phase as shown in this graft. Also, we know that with the faricimab, the PEDs had resolution faster than the eyes that were treated with aflibercept.  
 
So, overall, in the study, there was also safety shown in that the rates of RPE tears didn't significantly differ.  
 
Dr. Ehlers:  
Yeah. I think that those are really great data, and to be able to see that in the clinical trial format is super helpful, particularly as we're trying to customize our treatment decision-making.  
 
Jenny, this has really been a great discussion. Unfortunately, our time's up for today. I want to thank our audience and certainly, thank you, Jenny, for joining us, here.  
 
Dr. Lim:  
Thank you, Justis.