Goals of Therapy for Wet AMD


Lloyd Clark, MD, leads the discussion on the goals of therapy for patients with wet AMD and the role of anti-VEGF agents for treatment.

John W. Kitchens, MD: Lloyd, Roger talked a little about early treatment. Talk to us a bit about what are we trying to do and achieve with our treatments?

Lloyd Clark, MD: The current treatments, and we’ll get into this in a lot more detail, we’ve got great drugs to treat exudative age-related macular degeneration, wet AMD, and these drugs are fragments of antibodies or forms of antibodies. They’re biologics that target a specific growth factor. That growth factor does 2 things in wet AMD, it’s vascular endothelial growth factor. When we target VEGF with these drugs, there are 2 mechanisms of action of vision loss in wet AMD. The first is the neovascular component itself, this net of blood vessels that grows underneath the retina. We want to try to get that abnormal blood vessel net to stop growing and regress because untreated it becomes a fibrotic scar, which is damaging to the retina. The first goal of treatment with these drugs is to inhibit the growth of neovascular complexes, and in some patients reduce the size of it, to limit the fibrosis.

In the acute phase, the most important mechanism of action for these drugs is to reduce swelling in the retina. What happens from these blood vessels is that they can bleed, and that’s toxic. The iron in blood is toxic to the photoreceptors, but in general, fluid in the retina is toxic as well, and these drugs have profound inhibition of leakage. One of the great things about these anti-VEGF drugs is that they inhibit leakage from these abnormal blood vessel complexes. The acute effect of VEGF inhibitors injected in the eye is to reduce leakage from these abnormal blood vessel complexes, and that reduced leakage causes a reduction of swelling, saving the retina or salvaging the retina to some degree. We think about these drugs as antineovascular drugs, but they’re almost like very strong antihistamines in the retina. They dry up leakage, and the leakage is what causes vision loss on a chronic basis. Both of those mechanisms are important.

John W. Kitchens, MD: Dante, you had mentioned the scans that we do to look at a digital cross-section of the retina. What do we see when we treat a patient with exudative AMD on these scans, and how do we follow patients with these scans?

Dante J. Pieramici, MD: I mentioned the OCT, or the optical coherence tomography, and it has changed everything for us in our field. We used to take a look and it was a lot of guesswork, how thick is the retina? We could see things like blood. But even with a contact lens on the eye, it was hard to know how thick the retina was. As I said, this is like taking an image and then a cross-sectional view of the retina. We’re taking a little pie section of the retina. You can see the different layers in the pie. What we look for is fluid causing thickening of the retina, we can get fluid under the retina. We can see the choroidal neovascularization, that Roger mentioned before, growing. I love that analogy, Roger, I’m going to probably steal that a bit, the driveway.

The OCT can show us all these things, and it’s a fairly noninvasive test and it doesn’t require any dye injection. It’s a photograph test, there’s no radiation involved or anything like that. You can do it multiple times, you can do it daily, and it’s not going to affect the retina negatively at all. It tells us if the diagnosis is wet AMD, dry AMD. It tells us how well we’re doing after we do the injections that Lloyd’s mentioned. We can see the patient back in a week or a month, and then we should start to see a response, meaning that there’s less fluid, the retina is not as thickened, and it can help guide our treatment. Visual acuity is often hard to measure, and it’s a bit subjective, and 1 person might measure it and the next day another person might get a slightly different measurement. The OCT is a very quantitative way of looking at the retina; we can measure the thickness. That’s what gives us a lot of confidence in whether these agents are working and how well they’re working, and whether we need to do the treatments more or less frequently. It guides us in our treatment, as does vision, but I think we have more confidence in the OCT data.

John W. Kitchens, MD: Lloyd mentioned this class of agents, the biologics. Dante, do all patients respond to these medications?

Dante J. Pieramici, MD: Like everything in the world, there’s large variance in how patients respond. Most patients with wet AMD show some level of response. Some patients, they dry up after one injection, and they look great. We have to maintain them on that injection because with age-related macular degeneration, these treatments are not cures, they’re a way of just maintaining. The patient says, “How many of these am I going to need?” And I often ask, “Well, how long are you going to live?” It’s a calculation of maintenance, this is a maintenance therapy. As I said, some patients dry up quickly, and maybe they need an injection every couple of months, every 3 months, and sometimes even every 4 months. There are other patients who never completely dry up even when we’re injecting them every month but, we can get them stabilized and keep them from getting worse. Then there are rarely patients who don't respond at all. Those patients make me wonder if maybe we’ve missed the diagnosis or something else is going on because in my experience, most of the patients who truly have neovascular or wet AMD show some level of response to these anti-VEGF agents. The vast majority do.

John W. Kitchens, MD: We have several, and it’s unbelievable to think that we’ve almost had these for 2 decades now, and they’ve been a game-changer for our patients.

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Transcript Edited for Clarity

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