Wet AMD: Understanding the Role of Anti-VEGF Therapy

Peter L. Salgo, MD: We’ve been dancing around anti-VEGF therapy, and why don’t we start off with the obvious questions. What is VEGF, and what is anti-VEGF therapy? Give some definitions for this.

Charles Wykoff, MD, PhD: So, VEGF stands for vascular endothelial growth factor. It’s a cytokine that’s released by a damaged retina in the back of the eye, which is the oil on the fire, if you will, to grow these normal blood vessels. We have really good data dating back now 10 to 15 years, where if you block VEGF, if you put in these drugs that specifically block this growth factor, then you can limit the expansion of the blood vessels and you can stop them from actively bleeding, which leads to visual benefit.

Peter L. Salgo, MD: So, that’s VEGF. What are the approved options now on the market for anti-VEGF therapy?

Charles Wykoff, MD, PhD: From an ocular perspective, we have 2 FDA-approved agents. From a medical perspective, in general, there are 3 agents that block VEGF. Aflibercept and ranibizumab are both on-label, delivered directly inside of the eye, and FDA approved for the treatment of wet AMD. And then, there’s bevacizumab, which is used off-label for the treatment of wet AMD.

Peter L. Salgo, MD: We’ll come back to bevacizumab in a minute. For the 2 that are on-label now, aflibercept and ranibizumab, what are the dosing and administration guidelines for these drugs?

Jared Nielsen, MD: We’ve alluded to that a little bit already in that most treatments start out monthly, and then we employ this inject-and-extend treatment algorithm where, when the disease activity is rendered inactive or stable, we try and spread the treatments out. By the way, many patients continue to require monthly treatment. In order to maintain those individuals’ vision, we have to treat them monthly on a chronic basis.

Peter L. Salgo, MD: And, when we talk about treatment, we’re talking about injecting this stuff into the globe, right?

Jared Nielsen, MD: Yes.

Charles Wykoff, MD, PhD: When you tell a patient that for the first time, and they never heard of it, they look at you cross-eyed and they ask, “You’re going to put a what in my where?” But it is a teeny needle. I tell patients, “Look, the needle is really small, it’s hard to see without a microscope, it goes into the white part of the eye, and it really doesn’t hurt.” And that’s true for the vast majority of patients.

Peter L. Salgo, MD: Do you use local anesthesia, then, on the globe?

Charles Wykoff, MD, PhD: We do, yes. And there are many different ways to do that. But, essentially, it should not hurt. There’s often a little irritation, because of the sterilization step that’s required to minimize risk of infection, but it doesn’t hurt. Patients tolerate it really well.

Peter L. Salgo, MD: When I hear, “Oh, there’s a little irritation,” it reminds me of putting in an IV. “Just a little pinch,” not necessarily.

Jared Nielsen, MD: My favorite part of every day is when I’m able to treat a new patient who’s just frightened to death, and as I walk out the door, he says, “Did they do it already?” I love that.

Peter L. Salgo, MD: And the potential toxicities of these drugs now?

Charles Wykoff, MD, PhD: The toxicities from the drugs themselves are exceptionally low. It’s unclear if there’s even a signal there at all.

Peter L. Salgo, MD: Really?

Charles Wykoff, MD, PhD: Really. If you look at the large trials, they’re not powered to see systemic safety in the way that we would like. There may be a signal from systemic VEGF blockade, but it’s really unclear, and I tell patients we have no strong evidence that I am changing their risk profile systemically at the time.

Jared Nielsen, MD: We’re really fortunate, in that fact, to have a medicine that has so few side effects. Really, the thing that I worry about as a clinician is having an infection associated with an injection, which is an extremely, very rare event. But if you have an infection, it can be a devastating complication.

Peter L. Salgo, MD: If you somehow get an intraocular infection, that can be catastrophic.

Jared Nielsen, MD: Correct. Again, a very rare event. But if it happens, you want somebody that has great expertise in being able to manage that. That’s another reason to have this treatment done by a retina specialist.

Peter L. Salgo, MD: So, we’re going to do this once a month, at least at first?

Jared Nielsen, MD: Yes.

Peter L. Salgo, MD: We’re going to choose among a variety of drugs. How do you decide which drug to start with, which drug to use? And then, we’re going to get to money, because some of them cost more than others.

Jared Nielsen, MD: Well, I certainly think, when we’re looking at how to treat a patient and we have these options before us, you have to decide what your goals of treatment are. For me, my goal of treatment is to try and get that lesion to dry out as fast as I can, to become as inactive as possible, and also to try and administer the least number of treatments over the course of their need for treatment.

Peter L. Salgo, MD: But isn’t that the goal for everybody every time?

Jared Nielsen, MD: It would be nice to be in a world where our only consideration is efficacy. In that world, this decision becomes very easy, and you use the on-label medications. But the world that we live in is such that there is a very disparate cost for these medications, and that plays a huge role. I think no one would use Avastin (bevacizumab) to treat patients if it weren’t cheap. If the agents were all the same price, there would be no one that would use bevacizumab to treat their patients.

Peter L. Salgo, MD: And bevacizumab is off-label.

Jared Nielsen, MD: Correct.

Peter L. Salgo, MD: How does your decision to treat differ from his, if at all?

Charles Wykoff, MD, PhD: I agree 100%. The goal is to dry these eyes out as quickly as possible and maintain them to be as dry as possible, with as few injections as possible. You minimize side effects and you optimize their outcomes.

Jared Nielsen, MD: The other thing I will add is that we always have to consider safety. The nice advantage in using the on-label medications is that they are manufactured and developed specifically for use in the eye. For bevacizumab, it has to be repackaged by a compounding pharmacy, and there are issues associated with the repackaging. Prior to recent endeavors, compounding in the ocular world was a Wild West endeavor, and, unfortunately, there are sentinel events that happened that have brought in additional regulations, which have helped. But even after these regulations have been put in place over these compounding pharmacies, we’ve had issues with the repackaging of this medicine. I have a hard time using this medication when I have to worry about some of the risks associated with repackaging.