Roles for VEGF Inhibitors in the Management of Retinal Diseases - Episode 2

Macular Edema Treatment Goals

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W. Lloyd Clark, MD, and Diana V. Do, MD, discuss their goals of treatment and the standard of care for macular edema.

W. Lloyd Clark, MD: Joe, first, welcome, great to see you. I wish we could be together in person for sure. What are your goals for treatment for these types of macular edema? Macular edema is the culprit here. Are your goals for treatment in all these indications the same, or are they slightly different? What are you trying to achieve across the board with this class of agent?

Joseph M. Coney, MD: As stated earlier, these medications are very effective across most of our disease states in terms of vascular problems. My primary goal with every patient regardless of the disease is to try to maximize the therapeutic options with the biologics that we have present. That means make sure that all retinas are dry. I typically try to dry the retinas out as much as possible. We know that when eyes have persistent fluid, whether it’s intraretinal or subretinal fluid, there are subtleties in different diseases, but typically these eyes don’t do as well. We have seen this in some of our smaller studies, some of our larger trials, so I am always trying to maximize the efficacy with those drugs. Once I get the retina stable, then my goal it so try to minimize the burden to the patient, and I normally instill a treat-and-extend type of approach. I try to extend them out as much as I can, and I try to customize my therapy based on when I think the fluid can recur. I use the OCT [optical coherence tomography] to help me guide when individuals need therapy, and if the fluid comes back, then I’ll try to decrease that interval by a couple of weeks.

But my initial goal is always to try to make sure things are dry. And it is also important to understand that different disease states are different, and if you have persistent fluid in some instances, you need to figure out what is the driving force in that particular eye, particularly when it comes to patients with diabetes. There is an inflammatory component as well. I think that we all will agree that VEGF is important initially in all these diseases, but at some point because of the chronicity of the disease, we may have to think about changing classes in order to maximize efficacy in those patients.

W. Lloyd Clark, MD: Diana, Joe is going for total dryness. There is a good bit of talk these days about tolerance of fluid in certain indications, particularly neovascular age-related macular degeneration [AMD]. In Northern California, are you shooting for total dryness? Do you tolerate some fluid; if so, what kind do you tolerate?

Diana V. Do, MD: Retinal specialists have learned over the past several years that the location of the fluid within or underneath the retina is important. For example, eyes with wet age-related macular degeneration can have both fluid within the retina, intraretinal fluid, or underneath the retina, known as subretinal fluid. Studies have also shown interestingly that intraretinal fluid is the most detrimental to vision, and I think all of us, Joe, Ehsan, and you, would agree that removing intraretinal fluid is key to giving the patient the best visual prognosis. Additional studies have also shown that subretinal fluid, when it is small amounts, can be tolerated and still be associated with excellent visual acuity outcomes. For myself, I try to remove all intraretinal fluid, but when there are small amounts of persistent subretinal fluid, I will still evaluate the patient and perhaps still be able to extend the treatment interval without eliminating all subretinal fluid.

W. Lloyd Clark, MD: Ehsan, are we establishing a new standard of care, particularly in AMD management, of tolerance of some fluid? We have enough clinical trials now. We have extended drug delivery methods that are probably not as meticulous in terms of drying of the retina as monthly injections with highly potent anti-VEGF agents. Are we reaching a new standard of care, or is the standard of care in AMD and all of these disease states still dryness, treat to dryness and maintain that? You do a lot of work in long-term outcomes of patients, particularly with large population databases? Is there a consensus in the community today?

Ehsan Rahimy, MD: It’s a wonderful topic for discussion here. We may be reaching that state where we potentially are tolerant to some degree of subretinal fluid. I echo everything Diana just said. Our goal is to get rid of intraretinal fluid first, especially in AMD, and we all can recall numerous patients we take care of where we do just that. They have persistent subretinal fluid. Then the goals of therapy are shifting toward long-term management and trying to reduce treatment burden for many of these patients. Some of them are coming in from retirement homes where they rely on family members for transportation, and so we have to be mindful of that over the long term.

You mentioned some of these real-world population-based large database studies that have been done, which unfortunately show us that vision, which is what we care about in the long term, slowly wanes. We have seen that in a number of clinical trials, long-term extension studies, such as CATT, that by year 5, patients are negative in their visual acuity. CATT, for those who aren’t aware, that is a comparison of AMD treatment trials, which is funded by the NIH [National Institutes of Health], comparing Avastin and Lucentis. This is one of our landmark clinical trials that was evaluating different treatments and regimens for macular degeneration. Numerous other long-term studies, IVAN was another one, have shown us that in real world, once we get far enough out, for whatever reason, we are losing vision.

People debate about it. Is it because patients are being undertreated? That certainly seems to be a possibility when you look at some of these large databases that show the actual number of injections patients are receiving on an annual basis, it doesn’t follow as strict a protocol as we saw in these clinical trials. Could it also be because of other factors though? Especially when you’re talking about macular degeneration, we know and we unfortunately take care of lot of patients like this where atrophy eventually settles in. It doesn’t necessarily have to be geographic atrophy, as we talked about, but long-term injections. This is, as I explain to patients, the dry portion of the disease process settling in and causing vision loss, and it begs the need for newer treatments, better treatments, things we can combine with our VEGF inhibitors. But to your original question again, we are entering a new standard where we are learning to tolerate some degree of fluid on an individual basis. We recognize that AMD is not the same disease process among any 2 given patients, and the goal ultimately is to tailor treatment to optimize an individual’s vision to the best needs for their day-to-day living.

W. Lloyd Clark, MD: It does appear that intraretinal fluid is bad, continues to be bad, and continues to be a target for us to have aggressive treatment of our patients with both AMD and non-AMD indications with VEGF inhibitors. But subretinal fluid doesn’t look too bad, and we’ve got enough data now to let us feel comfortable giving patients more leash, for a lack of better term, in terms of treatment if all they have is subretinal fluid.

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Transcript edited for clarity.