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The Future of AMD Treatments

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Daniel Chao, MD, PhD

Assistant Professor of Ophthalmology at the Shiley Eye Institute

The featured expert is Daniel Chao, MD, PhD, who is an Assistant Professor of Ophthalmology at the Shiley Eye Institute. He is a retina surgeon, clinician-scientist, and entrepreneur. Dr. Chao’s clinical focus is in the medical and surgical treatment of retinal diseases with a special interest in macular degeneration and diabetic retinopathy, retinal detachment, and inherited retinal diseases.

  • BrightFocus Foundation
    The Future of AMD Treatments
    September 30, 2020
    1:00 p.m. EDT

    Please note: This Chat may have been edited for clarity and brevity.

    MICHAEL BUCKLEY: Hello, I’m Michael Buckley with the BrightFocus Foundation. Welcome to today’s BrightFocus Chat: “The Future of AMD Treatments.” If today is your first time on a BrightFocus Chat, welcome. I’ll briefly tell you about BrightFocus and what we’ll do today on the Chat. BrightFocus funds some of the top scientists in the world. These are researchers that are trying to find cures and better treatments for macular degeneration, glaucoma, and Alzheimer’s. We take the opportunity through the Chats or through our website,, or a number of print publications to share the latest news from these scientists with families that are impacted by these diseases. I’d like to introduce today’s guest: His name is Dr. Daniel Chao. He is an ophthalmologist at the University of California, San Diego, and BrightFocus has a really great opportunity to partner with him on a research grant from our Macular Degeneration Research Program, and we’ll have the opportunity to hear about his work today. Dr. Chao is what’s known as a clinician-scientist. It means he divides his time between seeing patients in the clinic in San Diego and also doing some of the most cutting-edge research in the world, so that’s why we thought he’d be a great guest today, because he has one foot in the daily practice of vision health and the other foot in researching new treatments. So, to that, Dr. Chao, I’d like to welcome you, and if you could just tell us a little bit about yourself.

    DR. DANIEL CHAO: Thanks so much, Michael, for that great introduction and for having me on this Chat. It’s always great to be able to talk directly to the patients to tell them about the newest things that are happening in macular degeneration. So, about myself, I grew up in the northern Virginia/D.C. area, and I think from an early age I was always interested in science and medicine, and that prompted me then to study biomedical engineering when I was an undergraduate in Richmond. And that led me then out west to do additional training to get my medical degree, as well as my Ph.D. degree, because I really wanted to go on this physician-scientist track, where I could both see patients and use science to develop new treatments. And so, then, fast forward now, after finishing my training as an ophthalmologist and as a retina specialist, as Michael said, I am a retina specialist at the Shiley Eye Institute at the University of California, San Diego. I’d like to say I divide my time into three buckets: One is seeing patients and doing surgery, and also teaching residents and fellows; and then another third of my time is doing research in the laboratory, which is focused on developing new treatments for macular degeneration; and then a third part of my time is spent doing clinical trials—these are clinical studies—for new investigational medicines for macular degeneration and other retinal diseases.

    MICHAEL BUCKLEY: Before we turn to the current and future treatments, I want to just talk for a moment about COVID. You know, we all hear—I want to say common sense, but not everybody does it—but we hear basic things about social distancing and masks and handwashing and such. Is there something that people with age-related macular degeneration or glaucoma … is there something that is specific about COVID that they should be aware of or attentive to?

    DR. DANIEL CHAO: To the best of our knowledge, COVID doesn’t change, for instance, the progression or disease of glaucoma or macular degeneration. I think the key thing to point out is that patients with macular degeneration are generally in a high-risk group for getting COVID in that they are older. They usually have medical comorbidities, and so it’s important, obviously, to adhere to all of those precautions that we’ve been hearing about in terms of using masks, social distancing, and especially in the retina clinic, where we are often seeing these patients. Now, at the beginning of the pandemic, we had … essentially, we were only seeing patients with emergent conditions or emergencies; those would be things that are very sight-threatening, like retinal detachments. But we’d also see our patients that had been receiving regular injections for wet macular degeneration, and it’s very important to continue those treatments, because we know that they are very helpful in preventing progression of the disease, and we want to make sure that we can continue to maintain that vision.

    MICHAEL BUCKLEY: As your patients have returned to your clinic, is there a common question or concern or fear either about being in a medical setting? Is there something recurring that you and your colleagues have had to address?

    DR. DANIEL CHAO: There’s always that fear of going out and contracting COVID by going into a medical facility. A lot of my patients tell me, “Oh, well, this is really … the only time I really get out of the house a lot of times is for my visits for macular degeneration.” I would say, in our hospital facilities, we have very established protocols and strong things in place to make it as safe as possible. I think those have been very successful, so far. These are things like having every patient that comes in, their temperature is checked, they’re asked about COVID symptoms, and they’re all required to wear masks. In addition, we don’t have patients wait out in the lobby; we usually have them wait outside. We also thoroughly disinfect all of the rooms between each patient encounter, and we also do our best to keep the patients moving so that they are not waiting or spending excess time in the medical clinic to make sure they’re not getting any needless exposure, and, of course, all of the staff is masked. We’re wearing gloves. Obviously, for the exam, we can’t social-distance, but we take all of the precautions that we can. And I think, so far, it’s been very effective. I certainly haven’t heard of any transmissions from the clinic, and I would say, in general, these are pretty standard precautions, and really, there’s been very little evidence that patients have been getting COVID through these clinic appointments; it’s generally much more so in community-spread or being in gatherings, especially inside with other people.

    MICHAEL BUCKLEY: That’s a great reassurance. So, as we turn to today’s topic of the current and future AMD treatments, I’d kind of like to break it into those two sections. So, starting with where we are today, can you have a broad overview of—in general—in America, who has AMD?

    DR. DANIEL CHAO: Age-related macular degeneration, as the name suggests, is that this disease primarily affects older patients. This usually begins to present itself in the 60s, and it affects both genders, though it does have a preference for Caucasian individuals. Now, the first signs of macular degeneration … people probably wouldn’t notice on their own; it’s usually that it would be seen by an ophthalmologist or optometrist, and generally, what we see on examination are these lipid deposits in the center of the vision called the macula. These deposits are called drusen, and essentially, as ophthalmologists—especially in the early stages—we essentially just watch these growths of these drusen, maybe once yearly. As the disease progresses, these drusen get bigger.

    Then, at some point, it can then branch and lead to two types of advanced macular degeneration, and these are simplified and called the wet macular degeneration and advanced dry macular degeneration. What wet macular degeneration is, is that there is a growth of blood vessels underneath the retina. These are abnormal blood vessels that can break through the retina. They can cause scarring, as well as cause leakage of fluids, and you can think about it as a … like tree roots breaking through the sidewalk a little bit. And so, that’s one type of macular degeneration, and this is treated—we have treatments for this. This is treated with injections in the eye, which I’m sure we’ll talk about later. And then, the other form of advanced macular degeneration is called advanced dry macular degeneration—or geographic atrophy, as it’s already known—and what happens here is that instead of blood vessels growing, essentially the cells in the central part of vision start to die off, and it leaves blind spots in areas where the patient can’t see.

    MICHAEL BUCKLEY: When somebody has been diagnosed with AMD, what are some of the current treatments that are in a physician’s repertoire to work with?

    DR. DANIEL CHAO:  When the macular degeneration is still fairly early, meaning it hasn’t progressed to either the wet AMD or the advanced dry AMD, we usually recommend taking this vitamin cocktail. It’s called the AREDS2 vitamin—A-R-E-D-S-2. It’s a cocktail vitamin consisting of things like vitamin C, E, zinc, lutein, and zeaxanthin. The reason I would recommend this is that this particular cocktail of vitamins had been studied in a clinical trial and showed a 25 percent risk reduction from going from the more early AMD to one of these advanced AMD forms, so that’s something that has a modest effect and usually something that we’d recommend for patients with early macular degeneration.

    Now, when the macular degeneration becomes wet, then we start injections of medications, which inhibit a protein called vascular endothelial growth factor. This is a protein that’s been found to be very important for growth of these blood vessels and leakage. And so, we administer this through an injection in the eye. Now, that sounds like probably the worst thing in the world, but it’s something that’s actually very common in the clinic. We perform many of these injections, and patients, with time, actually get used to them pretty quickly and it becomes just part of their regular routine. This has been a really great advance for patients, because it can really halt the wet macular degeneration in its tracks. And so, when we administer this medication, we can really prevent further vision loss, prevent patients from going blind, and many times, we can improve it. So, really, we can stop the disease and keep it at a stable place.

    Now, one thing about wet macular degeneration is that it’s … I tell my patients this is a chronic disease, like diabetes or hypertension. We can’t … it’s not like we give you one or two or three shots and you’re cured. This is something that we need to administer repeatedly. In the beginning, we give it about once a month, and depending on how you respond, then we potentially can lengthen the interval for the injection to once every 2 to 3 months, depending on the patient, but this requires regular follow-up with the patients. I tell any patient with new wet macular degeneration that we’re going to be seeing each other a lot, and it’s something that we follow, then, for many years and that patients will need to get these injections at some regular interval for the rest of their life. As we move to the dry macular degeneration … so, unfortunately, currently we don’t have any treatments for the advanced dry macular degeneration, but there’s a lot of exciting studies that are currently in the pipeline.

    MICHAEL BUCKLEY: We’ll get to those in a couple of minutes. Dr. Chao, we have a few questions that are kind of on the points you’ve been discussing here. A listener from Arizona is wondering, is there … any of these current medicines have the ability to reverse vision loss—any vision loss—that may have occurred?

    DR. DANIEL CHAO: Usually, for these medications that we’re giving right now, they will prevent further vision loss. If we catch it really early, what it can do is maybe help improve it a little bit, but really, what we’re doing is maintaining vision from where it is right now.

    MICHAEL BUCKLEY: One other question before we move on, a listener in Maryland … kind of a two-part question. Is there an overall percentage … or what percentage of dry AMD moves to wet, and then kind of parallel that, when somebody gets wet AMD in one eye, what is the percentage or likelihood of it going to the other eye? This is sort of a prognosticating type of question that our listener has.

    DR. DANIEL CHAO: We know when you have macular degeneration, what we call it now … we can rate it with different types of ways, usually with the size of the drusen. But when you get to what we call intermediate AMD, then we say you have about a 10 percent risk per year, then, to develop the wet AMD. So, if it advances, I would say about 10 to 25 percent will then progress to the wet AMD. And I think, certainly, if you’ve gotten wet AMD in one eye, you’re certainly at higher risk for getting wet AMD in the other eye, and so that’s something that we watch very carefully because we’re treating that eye, and I would say maybe about a third of the patients in the next 5 years would also get wet AMD in the other eye.

    MICHAEL BUCKLEY: Another question has come in about these treatments. Is there a sense of how well the existing wet macular medications … on the whole, how well do you think that they work?

    DR. DANIEL CHAO: I think, in general, for most patients with wet macular degeneration, these work really, really well, and the way that we usually monitor these is by looking at the fluid or the swelling in the eye. So, almost all of these medications work very well for these. Now, there’s a small fraction of patients—maybe about 20 percent—that don’t completely respond to these medications, and sometimes we can … there is about three medications that are currently on the market, and sometimes we can … they’re all very similar, but sometimes we can switch back and forth and get some type of increased response. But I would say, in general, for the vast majority of patients, these medications work very well to stabilize the patients.

    MICHAEL BUCKLEY: In addition to the treatments that you outlined—the AREDS vitamin supplements—are there other things people can do to help preserve their vision or at least hold off further loss, in addition to the treatments at the doctor’s office?

    DR. DANIEL CHAO: Absolutely. I think one critical thing is early diagnosis, especially for wet AMD, where we have treatment. Because we know that the earlier you can … the earlier that you are diagnosed with wet macular degeneration, the better your vision is. So, the best predictor of how, in terms of the vision that you have with wet AMD, is the vision that you come in with when you present with that. And so, I think early screening and home screening are really important. There’s a couple of things that we recommend. One is something called an Amsler grid. This is essentially a piece of … it’s basically a piece of graph paper, and what we ask patients to do a couple of times a week is to cover an eye and look at this Amsler grid, and if you start to see some sudden changes where the lines get very curvy, then those would be signs to give your doctor a call and get checked out. So, that’s one way—an easy way—of screening yourself for macular degeneration. The other thing is that there are also home monitoring devices. One is called the ForeseeHome, which essentially is this device that you have at home and you do what’s … there’s a visual field test there, so you’ll go in and perform that test a couple of times a week, and if there’s a big change it will then notify your doctor if there’s change and that you should come in to get checked out. So, I think the early screening is really important to preserve the vision in macular degeneration.

    MICHAEL BUCKLEY: Dr. Chao, as we pivot to the future, I was wondering if you could start off with a state of the AMD assessment. When you look at what you and your colleagues are currently doing, what do you see as some of the limitations or challenges that make you and others work toward improvement?

    DR. DANIEL CHAO: I’d like to divide it into two main buckets. As I’ve said, one is for wet macular degeneration; the other one is for dry macular degeneration. For wet macular degeneration, I think the big picture is that we now have very effective treatments that can prevent and stabilize vision for wet macular degeneration. The really big news, now that we have, is to have treatments that last longer—and, as I mentioned, many times these patients need to come in once a month, and you can imagine how that can be a very heavy treatment burden. There are also family members that need to come with them, and so there’s a lot of effort and people involved in making that happen. And so, for a long time, people have worked on methods that, perhaps, we can get these medications to last longer so patients don’t need to come in as frequently and don’t need to get shots as frequently, and there are a number of approaches that are currently in clinical trials. These are things like various sustained-release drug delivery. There’s even a surgical implant, and there are also gene therapies, which produce this inhibitor of the vascular endothelial growth factor as well, and a lot of them have very promising results. None of them are available quite yet, but I’m very optimistic in the next 5 years or so that, certainly, these will be coming on to the market. Now, in terms of dry macular degeneration, I think this is where there’s been a real big unmet need in that we really don’t have any treatments right now to prevent the growth of this dry macular degeneration. So, right now, there are … but I think that is changing now. It’s been a problem that people have been working very hard on for a long time, and I think we’re starting to make progress right now in that there are clinical studies with injections of a medication and a pathway called the “complement pathway.” This is a pathway involved in inflammation, and they’ve shown some promising results in decreasing the growth of these advanced dry AMD lesions, and so I’m hopeful that these studies will … the larger studies will also come out positive and that this is also something that we can offer to patients in the near future, as well.

    MICHAEL BUCKLEY:  Because of COVID, all of us hear the phrase termed “clinical trials” in the news every day, but I think I could speak for a lot of people that there is some mystery. It’s a term you’ve heard of but don’t quite understand. So, in vision health, how do clinical trials work?

    DR. DANIEL CHAO: The clinical trials are done primarily to assess whether a new medication is both safe and whether it’s effective for a new treatment, and so the way that it works is this. I think the benefits for patients is that it potentially allows you access to a medicine before it might be available on the market. So, for diseases that have no treatment or cure, if the drug is successful, then you may have access to it earlier. Now, the other thing, kind of more on the global standpoint, is that, whether the drug is effective or not, we will learn a lot of these things from these clinical trials, which will benefit all patients, in general, moving forward.

    What happens is that if you are interested in a clinical study, first you are screened to see if you are eligible for that. You’ll go through a lot of tests. You’ll probably get some blood work. We’ll check your vision, probably a little bit more than you would have in your normal visit. And then, if you are qualified for the trial, then you are what’s called randomized. So, to figure out whether a drug works or not, we need to compare the investigational drug to, then, either the standard of care or what’s called a placebo if there’s no standard of care. So, people are put into one of these two groups, and the patients don’t know which group they are in and the doctors also don’t know which group they are in, so they’re called what’s called “masked.” And so, that really helps to lead to the objectiveness of the clinical trial. Once you’ve been randomized, then you’re going to receive either the drug treatment or you’ll be receiving what you would normally get in the clinic, and then over time you will then be … you’ll go through the study, and then we’ll unlock the results and see whether this treatment was effective or not.

    From a patient standpoint, the way that it differs from a regular clinical visit is that, number one, there’s a bit more testing and the exams are much … they’re a little more involved and thorough. I like to tell patients that we’re really going to be looking very, very closely at your eyes to see if there’s anything that’s going on. And then, also, it’s a little bit different in that there’s usually a clinical coordinator—it’s almost like a concierge kind of thing—where patients are led through that trial at every step of the way.

    MICHAEL BUCKLEY:  This is really helpful.  Dr. Chao, I know you said that you actually are running a clinical trial. That type of research … what’s that like to do? Does it give you a lot of hope for the future? What have you personally taken out of that experience surrounding a trial?

    DR. DANIEL CHAO: I think what’s really exciting about that is that these trials … we’re really very close to being at a point where we might have new treatments for patients. So, a lot of times the trials that we do, they’ve been done in earlier stages where the drug has been shown to be safe, and then another trial usually shows that there’s some kind of efficacy. So, after the end … after we’ve performed this clinical trial and there are positive results, then this could be a drug that then would come into the market in the next few years. And so, it’s very gratifying to be a part of that effort, to be involved in seeing whether these treatments work and bringing new treatments to the market.

    MICHAEL BUCKLEY: That really seems like an opportunity for both you and your patients to get a little glimpse at the future. Dr. Chao, how would a patient, whether that’s in a trial how does—with eye medications—how does someone know that the treatment is safe and effective?

    DR. DANIEL CHAO: That’s a great question. There are a number of steps first to determine whether it’s safe—all of these clinical studies are highly regulated by the Food and Drug Administration. So, the first thing is that, say there’s some exciting work in the lab, then first there’s a lot of work to make sure that the drug is at a very high purity, that the manufacturing quality is very high, that there’s no contaminants before it can be first tested in humans. And then, those first trials are called phase 1 or phase 1/2 studies, and these are testing it in either healthy volunteers or patients who have very end-stage disease. So, these are patients that are not necessarily thought to be able to … may not necessarily benefit from the treatment directly, but it really helps to determine whether the drug is safe.

    And then, once we have an idea that the drug is safe, then we move on to the next clinical trial, which is generally called a phase 2 trial, in which we pick a population of patients with the disease and those without, and we get a general idea of whether there’s any hint that the drug may be effective at this point. And again, we’re also collecting more safety data, as well. If that’s acceptable, then we would move on to what’s called the phase 3 trials, which are larger trials, again, testing the drug versus a comparison arm. And then it’s at that point, if those larger trials are successful and show positive results, then potentially it can then on to the market.

    One thing to say about clinical studies is really to make sure that you’re participating in a legitimate clinical study and not something that’s not regulated by the FDA. There are a couple of ways to look at it. I think the first thing that you can look at is there a website of clinical trials—it’s called, which will show a listing of all the clinical trials. Now, that doesn’t necessarily mean, again, that those are all legitimate trials. I think the other thing is certainly to ask your doctor about it to make sure it’s a trial that he’s heard of. Another big red flag is if you have to pay to be in the clinical trial, that’s definitely a big red flag, because all of these clinical studies are usually sponsored by the companies, and the treatment should be free of charge.

    MICHAEL BUCKLEY: Related to that, I think that some of our callers over the last few months have mentioned that they’ve heard some news stories about some stem cell clinical trials that they had concerns about.

    DR. DANIEL CHAO: In terms of stem cells, there have been a couple of very early trials using stem cells. These are usually cell transplants that are put in patients who have very end-stage disease, and I would say those stem cell trials are still in the very early stage. I think it’s very exciting, but it’s still a long way away before we know whether this will be successful or not. Now, there has been, also, this explosion of these stem cell clinics, and these are places that offer stem cells as a … they report it as a treatment. It could be for macular degeneration, it could be for glaucoma, it could be for a bunch of different things. So, these are not part of a clinical trial. These are clinics that are taking stem cells—usually out of the patient’s body, sometimes from their fat—and then going ahead and then usually injecting it into their eye or injecting it through an IV. And so, these are not regulated. These have not been tested to make sure that they are safe and efficacious, and it hasn’t gone through this very regulated process. So, I would strongly discourage you from going for one of these treatments. I think this is another thing—that speaking to your doctor will be really helpful to help you identify which of these trials are legitimate and which ones may not be.

    MICHAEL BUCKLEY: We really appreciate your note of caution on that. In the remaining couple of minutes here, I just want to get to one question that a number of people have asked today. Genetic … is AMD genetic? One person asked about, is it sibling-to-sibling? We’ve had a few people ask about parent-to-child—you know, predisposition. I was wondering if you could address that.

    DR. DANIEL CHAO: I would say there’s a lot of different factors that play into whether you get macular degeneration. I think genetics is a part of it, but the environment also plays a big role. Genetic testing isn’t something that we frequently do. If your family members, like your parents or other members of your family, have macular degeneration, you do have a slightly increased risk, and so I would recommend going for, certainly, a screening visit with your ophthalmologist. That being said, it’s not like a one-to-one thing, where if your mom or dad had this that you definitely will have it, and currently, genetic testing for macular degeneration is not something that’s routinely recommended for macular degeneration.

    MICHAEL BUCKLEY: That’s good to know the current state of that. So, Dr. Chao, as we conclude the conversation today, in your experience in the clinic and in the lab, is there one big picture piece of advice you’d like to give your patients or would like to give the listeners today?

    DR. DANIEL CHAO: I think one thing is that we’ve come a long way in macular degeneration. I would say even 15 years ago, patients were going blind from wet macular degeneration, and we’ve made incredible strides now to have medications that will help prevent blindness and stabilize vision. What I’d like to give all the patients out there is, certainly, there is a lot of hope. I think we’ve gone a long way in wet macular degeneration, and we’re right on the cusp of having some really exciting treatments for dry macular degeneration. And even if we may not have something right away, there’s a lot of people working very hard to find new treatments, and these things are always around the corner, and there are multiple clinical studies going on. And so, I’d certainly take away that there’s a lot of hope for the future in terms of treatments for macular degeneration.

    MICHAEL BUCKLEY: Thanks. That’s good to know because it’s something so critical to our quality of life, like vision. This is really very helpful information that you’ve shared with our audience. And so Dr. Chao, on behalf of the audience today and BrightFocus, I just really want to thank you for all you’re doing. You’ve really shown us that through research and greater public awareness there really is hope on the horizon for wet AMD, and I know that the research that you’re working on with BrightFocus funding is particularly exciting and encouraging. So, I just really want to thank you for all you’re doing.

    DR. DANIEL CHAO: It’s a pleasure, Michael.

    MICHAEL BUCKLEY: To our audience, this concludes today’s BrightFocus Chat. You can call us anytime at (800) 437-2423. You can find us on the internet at On behalf of BrightFocus, I just want to thank you very much for joining us today, and we’ll talk with you next month. Thanks.

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