anti vascular endothelial growth factor therapy

Let's talk about Verisimab.

Verisimab, ANG2 inhibition, anti-VEGF therapy.

Is it more of an increase in molar dose of the anti-VEGF therapy or is ANG2 inhibition a real thing?

So I'm an ANG2 fan.

I've been an ANG2 fan for a really long time.

I've said this before, but probably not in a recording, that Mezzi is a sleeping giant.

I think the Mezzi indication can be really big.

I've been involved with the IL-6 programs with Genentech, and now more recently the IL-6 anti-VEGF combination programs from Kodiak and Peak, Pinnacle, and now Alto for DME.

But I will say this, even if you don't think retina is the best field, I will say there's no field in subspecialty in ophthalmology that sees such rapid turnover of clinical trial results, money entering the field for investment in new medications.

And yet, a tough bar to clear because we have really good medications in the name of anti-VEGF drugs that work really, really well.

So it's kind of an interesting conundrum.

And we have had multiple trial readouts in the last couple months.

And this was looking at tyrosine kinase inhibitors versus gold standard, Aflipercept, Ilead, to those of you out in the community.

as a non-inferior option for wet age-related macular degeneration with greater durability.

So again, it's been very tough for companies to design trials to beat anti-VEGF.

I don't think anyone feels that anti-VEGF doesn't work.

I look forward to a fantastic conversation.

Let's discuss second-generation intravitreal anti-VEGF therapies.

And maybe, Manjot, let's discuss neovascular AMD and the burden of treatment in that condition.

Yes, Diana.

But after seeing patients for even years and years later, there still is a lot of anxiety and anticipation about the injection itself, in addition to, again, the time that it takes out of their day-to-day lives.

And

we've seen through multiple abstracts and presentations that when we switch to these second-generation anti-VEGF agents, either aflubracept, 8 milligrams, or furosemab, there are benefits.

Michael, let me ask you about the Truckee study.

You know, I've been operating diabetic eyes diabetic detachments for over 30 years.

And in the past, peeling membranes was a lot easier than after I started pre-injecting them with anti-VEGF or patients had been injected with anti-VEGFs, let's say for edema or whatever.

When you go to operate those eyes, the fibrovascular tissue is severely adhering to the retina and it's much harder to peel.

Whereas in the past, you could go and it would separate much easier.

So I think the fibrosis component, we see that in patients that have been treated previously with anti-VEGFs, the surgeries are harder, but also in patients that have severe renal disease.

And it's because of the inflammatory components.

So you've already hit a couple of questions I was going to ask you.

I was going to ask about the protocol S, which you already responded.

I'm Dr. Matt Starr, Associate Professor of Ophthalmology from Mayo Clinic and editor of the podcast Retina.

This week, we're featuring an article entitled, Effectiveness and Safety of Biosimilar Antivascular Endothelial Growth Factor for Retinal Diseases, a Systematic Review and Meta-Analysis by Madhra Pandeya, the first author, and Tina Fafeli, the senior author from the University of Toronto.

As we know, anti-VEG therapy has transformed the management of wet AMD, DME, and renovated inclusions.

But repeated injections create substantial financial burdens for our patients and healthcare systems.

a 3d view of that carpet the subfloor the pipes and everything underneath so we can then see is there a collection growing or is there um is that sand starting to collapse the the bottom layer that's there or is it starting to degenerate that lower layer is there more sand that's growing and we can quantify that we can quantify that both in photos and in oct And then we can also see, like I mentioned, that collection of blood vessels starting to form.

And if it is, but it hasn't leaked yet, we may watch it really closely because... an anti-VEGF injection isn't necessarily going to dry up fluid that's not there.

But if we have that collection of blood vessels, we may work with a retinal specialist to say, do you want to see this patient now or do you want me to keep monitoring until they have fluid development? And oftentimes in our area, they want us to keep monitoring it until they see fluid development because they've got hundreds of patients that are getting injections every day.

So we could watch that for a period of a year and not see any change.

They found that eyes that went on to tear had pigment epithelial detachments that were, on average, about 210 microns taller at baseline than in eyes that did not tear and larger in area.

Fibrovascular detachments, subretinal fluid, sub-RPE, clefts and radial hyperreflective lines were also associated with tears, while the choice of anti-VEGF drug was not consistently associated.

The strength is a registered protocol, with results that held when each study was left out in turn.

The catch is that most studies were at moderate to serious risk of bias, and the authors rate the certainty of evidence as very low.

My take.

Early or exploratory? In my view, it gives us a useful set of OCT signs to look for, starting with the oblique band.

What it can't tell us yet is whether these eyes respond to anti-VEGF treatment.

Most were already scarred when the lesion was found, only half were treated, and intraretinal fluid persisted in most of those followed up.

And with bevacizumab, which is also used if we start with the first line setting, I think that bevacizumab based on some retrospective series and subgroup analyses is actually useful in low-grade serous as well as what we know with high-grade serous.

So I think bevacizumab anti-VEGF medication is applicable there.

But if we go back to the first line setting, it's really important for patients with low-grade serous ovarian cancer to have the best chance of surgery.

Surgery is the mainstay of low-grade serous ovarian cancer treatment.