Priyatham S. Mettu, MD
Priyatham S. Mettu, MD, is a Duke University retina specialist who is testing new treatments and new imaging technologies for age-related macular degeneration.
Priyatham S. Mettu, MD, is a Duke University retina specialist who is testing new treatments and new imaging technologies for age-related macular degeneration.
AMD: Your Questions Answered
September 26, 2018
1:00–2:00 pm EDT
Transcript of Teleconference with Dr. Prithu Mettu, he is currently a retina specialist at Duke University in North Carolina.
The information provided in this transcription is a public service of BrightFocus Foundation and is not intended to constitute medical advice. Please consult your physician for personalized medical, dietary, and/or exercise advice. Any medications or supplements should be taken only under medical supervision. BrightFocus Foundation does not endorse any medical products or therapies. Please note: This Chat has been edited for clarity and brevity.
MICHAEL BUCKLEY: Hello, I’m Michael Buckley with the BrightFocus Foundation. Welcome to today’s BrightFocus Chat. Today’s topic is “AMD: Your Questions Answered.”
If this is your first time joining us today, we’ll briefly tell you about BrightFocus and how the Chats work. BrightFocus funds some of the top researchers in the world. These are scientists trying to find cures and new treatments for macular degeneration, glaucoma, and Alzheimer’s. We take the latest and recent news from these scientists and share them with families who are impacted by these diseases. We do this through Chats like today’s, as well as a number of free publications and materials that are available on our website, BrightFocus.org.
Let me tell you about today’s Chat. We are joined from North Carolina by Dr. Prithu Mettu. He’s a Duke University retina specialist doing some great work on testing new treatments and new imaging technologies for age-related macular degeneration. Here at BrightFocus, we’ve been extremely fortunate to have the opportunity to work with Dr. Mettu through our macular degeneration research program to support some of his early-stage research. Dr. Mettu, I’d like to welcome you to today’s Chat. I know we had the opportunity earlier this year to work together. I was wondering if you could just tell the audience a little bit about yourself and what you do at Duke University.
DR. PRITHU METTU: Well, Michael, thank you, and thanks for having me. It’s great to be back with you again. I am, as you mentioned, at Duke University. I am a clinician scientist here at Duke. What that means is that I wear a couple of different hats. As a clinician, I have an active practice taking care of patients with age-related macular degeneration, diabetic retinopathy, and other macular diseases. And when I’m not in the clinic, I am in the lab, and my research program is focused on trying to identify new targets and new and better ways to treat the subset of patients that have wet macular degeneration that aren’t helped optimally by our currently available therapies. And then, additionally, I’m involved actively in clinical trials of new medications for macular degeneration, as well as collaborating and consulting with organizations that are trying to develop new drugs and new devices for patients with these diseases.
MICHAEL BUCKLEY: That’s great. Thank you for filling us in on that. Before we get to some of the questions, out of curiosity, what made you want to become a doctor and a scientist?
DR. PRITHU METTU: What drew me specifically to this role is that I saw that there was a unique opportunity within ophthalmology. Sight and vision is such an important part of all of our day-to-day lives. And most of us, as we’re going through our day-to-day lives, we sort of take that for granted. But when it’s affected and it affects our day-to-day lives, it really has a tremendous impact on quality of life. In this role, I’ve been fortunate to have an opportunity to directly impact patients one at a time—taking care of them and just trying to improve their vision—and then, through discovering new knowledge and developing new technologies, the opportunity to change the ways that we’re able to approach disease and transform the care of these diseases. And I find that duality very fulfilling.
MICHAEL BUCKLEY: That’s great, and I would agree. Dr. Mettu, as you can imagine, a number of questions submitted today have to do with injections in the eye to treat macular degeneration. Several people asked, “How soon will they develop a drug that’s better than current therapeutics to treat wet AMD? And, specifically, will these make injections less frequent, or are we working toward a world where there are no eye injections?” Feel free to take that anywhere you want in explaining the injections currently and in the future—however you want to start that topic.
DR. PRITHU METTU: Sure. I think that question is a very good question, and it speaks to the problem of what we call “treatment burden.” Frequent, often monthly, injections mean that patients have to be in their retina doctors’ offices eight to 10 times a year. That means a family member has to accompany them. That means that the doctors’ offices have to have a way to accommodate them and provide the necessary treatment, and that’s a pretty heavy burden for patients and their families, and for the health care infrastructure.
The good news is, I think, that there are efforts underway to address that. We know that there is a drug that just recently finished—completed—a Phase III with some positive results. The drug is called brolucizumab.* There are some indicators that it may allow less frequent dosing. We’re still waiting on some additional data to kind of really understand how effective it will be for durability.
And then, there are a couple of others underway to develop sustained relief and drug delivery approaches. There’s one approach with a surgical implant, where the drug can be refilled on an every-3-month basis, and that just completed a Phase II study, so that’s still in development. There are some earlier-stage efforts underway to develop a 6- to 8-month drug delivery device to decrease the need for injections. And then there’s a couple of companies—one that’s working on an eye-drop formulation that the patient can administer on a daily basis. And then there have been efforts underway for a pro-medication that could be taken, although I think the most recent effort from a company called Tyrogenics—my understanding is that is on hold at the moment. The bottom line is that there are a lot of efforts underway to address this larger issue of frequent monthly injections, and I’m very optimistic that within the next several years that we’re going to see one, if not more, of these modalities come to the fore and help us to manage that for our patients.
MICHAEL BUCKLEY: That’s great. Very encouraging signs of hope there. I appreciate you using the phrase “treatment burden,” because I think that addresses so many parts of this—whether it’s the patients getting transportation to a medical office, to the health care system, Medicare and private insurance—and I think it sounds like there are things in the works that would really help all parts of that equation.
We had a question about injections. Someone says they’ve had four injections so far and they don’t seem to notice any difference. Is that something that takes a while to notice, or do you have thoughts about that?
DR. PRITHU METTU: Yeah. I’ll preface by saying everybody is an individual. So take what I am about to say with a grain of salt because individual results will vary. But in general, the visual benefit is recognized by the patient within the first three to four shots. So if there hasn’t been a substantial vision improvement after the first three to four shots, the chances of seeing a “wow” response after that point are less likely.
There are certain circumstances where a patient doesn’t respond well to one particular medication. Switching to another medication may help them to get over that hump. There are also certain cases where the disease is a little bit more complex and requires some adjunctive treatment approaches, and sometimes that can help for vision. In general, the vision benefit in terms of the improvement is seen in the first 3–4 months.
That being said, I think it’s important to remember that these drugs are ideally for improving vision, but definitely for maintaining vision. We know that if wet macular degeneration is not treated, the natural history is that patients will continue to lose vision, so the drugs at a minimum should be able to maintain vision in most patients.
MICHAEL BUCKLEY: That’s interesting. I’m glad you mentioned that. So a realistic definition of success, if I’m hearing you correctly, would be kind of maintaining the status quo?
DR. PRITHU METTU: Yeah. I think if you look at patients receiving therapy who started off with what we call—if you look at the trials in patients who were diagnosed and who were subsequently started on these anti-VEGF medications, around two-thirds, 65 to 70 percent, were able to maintain good visual acuity, meaning vision better than 20/40. That’s being able to see street signs or being able to read without too much difficulty if they were continuing to receive therapy. But again, that’s a population base, and each patient’s going to be different. And it’s important to discuss the specifics of your case if you’re not.
MICHAEL BUCKLEY: That’s good advice. At least for now, one more question about the injections. We may go back as the questions come in. A caller was wondering, are there side effects to these injections?
DR. PRITHU METTU: In general, the main side effect that we are concerned about, which is infection, is rare. That maybe happens in about 1 in 1,000 or 1 in 1,500 cases, and doctors who administer the injections take approaches to minimize that risk. That’s the main thing to be aware of. As far as the medications themselves, they’re generally pretty safe. We’ve had these drugs available now for about 12–13 years, and really the only thing that I talk about with my patients—patients who have had a recent stroke or a recent heart event—we talk about whether it might be prudent to have a delay in treatment or a “drug holiday,” if you will, to let them recuperate, because there is some thought that, as these drugs get into the body, they might have an effect on someone who is recovering from one of those events. In general, the medications are pretty safe.
MICHAEL BUCKLEY: That’s good. On that point, are these injections something someone could get indefinitely, or at some point do they lose their vitality or purpose? Is it more of a fixed time window?
DR. PRITHU METTU: The good news is that they can be administered and received indefinitely. In fact, what I tell my patients who have wet macular degeneration is that we’re going to get to know each other pretty well, because the reality is that the drugs help to manage the disease. They don’t cure it, so the vast majority of patients need treatment for life. There are multiple studies now that have been published that have shown that long-term sustained treatment to keep the disease under control is the best approach for maintaining their vision—that when you back off treatment or undertreat it, that’s associated with a greater risk of losing vision.
MICHAEL BUCKLEY: Let’s switch gears to stem cells. We have a few good questions from our BrightFocus constituency about stem cells. Is there work going on in the stem cell area as far as macular degeneration? And if you wouldn’t mind, in your answer, could you explain what stem cells are? Because I feel it’s something all of us hear about in the news, but we might not know what a stem cell is. Do you have anything you could update us on in the world of stem cells and treating macular degeneration?
DR. PRITHU METTU: Sure. When it comes to stem cells, they can be defined differently, but in a big-picture sense, you can think of these as cells where their fate is not yet determined. In the right study, they can be programmed to assume a number of different cell types, to become a different cell type, or to have a lot of different functions, and they can be obtained from different sources. They can be obtained from umbilical cells, embryonic cells, from adult tissue, and also from the bloodstream. Broadly, there are really two different approaches to stem cells. One is kind of what most people think about, which is cell replacement, meaning you’re taking these stem cells and you’re putting them under conditions that these cells can replace the cells that we’ve lost. There’s been a number of trials and companies that are trying to develop that, and the idea is that they could regenerate into cells that have been lost as part of the disease. Efforts in this area are in the very early stage.
There have been some high-profile studies out there talking about, “Oh, this could be good,” or “This holds a lot of promise.” And while some of these very early results that have been publicized are promising, there are a very small number of patients. Those studies really are to establish safety, and we’re a ways away from understanding and fully realizing the potential benefits of that technology—that is, as it relates to cell replacement, where I think we’re a ways off in seeing that come to clinic.
MICHAEL BUCKLEY: I appreciate it.
DR. PRITHU METTU: The second approach, just briefly, is basically supportive therapy—so cells that aren’t replacing cells, but they’re pumping out healthy factors that can help to repair damaged cells or prevent further loss. I think that is a much more viable approach, and there are several development initiatives for that.
MICHAEL BUCKLEY: One of our callers was wondering: will they ever be able to grow a whole new retina for replacement in the eye through stem cells?
DR. PRITHU METTU: At the moment, that’s what I would call kind of a fantastic goal, meaning if we could get to that point, we could really offer a lot to patients who’ve been harmed by retinal diseases. That’s still what actually would be a national attitude that’s identified as an audacious goal to try to do that, and there is science that is being conducted to understand how to get to that point. But we’re still many years away from that.
MICHAEL BUCKLEY: That’s certainly a great goal to aim for. I’d now like to turn to some questions about nutrition and vitamin supplements. Before I do that, I want to remind our listeners that BrightFocus has a free publication called Macular Degeneration: Essential Facts. It gives some of the specific vitamins and dosages that Dr. Mettu may be talking about over the next couple of minutes, so if it’s a little hard to take accurate notes about different types of vitamins, I just want to mention that up front. So, Dr. Mettu, I was wondering if you could tell us a little bit about AREDS. The first question we have is, does the effectiveness of that fade out over years of use?
DR. PRITHU METTU: The AREDS vitamins come in several different formulations—basically a cocktail of antioxidant vitamins—vitamin C, vitamin E. In the past, there’s been some formulations that include beta-carotene—a form of vitamin A—as well as zinc, lutein, zeaxanthin, and copper. That was initially studied in the early 2000s, and then more recently in the past decade. And the bottom line is that this cocktail of antioxidant vitamins was used to decrease the risk of progression to advanced macular degeneration, which is primarily advancing the risk of developing wet macular degeneration. So my patients who have what we call high-risk, dry, age-related macular degeneration—the patients who are in the early stages of the disease who haven’t developed necessarily vision consequence—those are the patients who are the right folks who take this formulation of vitamins.
Over time, the vitamins themselves don’t necessarily lose their efficacy. But if a patient develops more advanced disease in both eyes—so let’s say a patient develops wet macular degeneration in both eyes in spite of the vitamins—then really the utility of the vitamins isn’t really applicable anymore. So those patients—I tell them that they can stop it. But that’s kind of the background on those. They come in different formulations, and the convenience of what’s available at the drug store is that everything’s in one pill. But if you know the correct amounts, you could, in theory, kind of assemble that formulation from its component parts. So there’s multiple ways to get there.
MICHAEL BUCKLEY: Interesting. One of our callers was wondering, are generics okay in this situation?
DR. PRITHU METTU: Yeah. I mean, I think with the caveats, you want to make sure that the supplier of the generic is a reputable source. But I think it’s reasonable to do generics, as long as the amount of the vitamins are equivalent to the AREDS and that it’s not at significantly higher doses.
MICHAEL BUCKLEY: We have a question that came in a few minutes ago that Dr. Mettu thought was interesting: Is there a connection between glaucoma and AMD? Does having one disease increase the chance of having the other—glaucoma to macular or macular to glaucoma? Is there any connection or associated risk?
DR. PRITHU METTU: There’s no data that suggests that one disease necessarily leads to the other. It’s possible that there might be some overlap in terms of risk factors. Age, I think, is one risk factor that’s probably common to both because we kind of see it in older individuals; and there may be certain environmental risk factors. But the underlying disease mechanisms I think are very unique.
MICHAEL BUCKLEY: A couple of new questions have come in. Someone is wondering that if they’re just diagnosed with dry AMD, what’s the next path? Do they stay with an optometrist, or is there a need to go to an ophthalmologist or a specialist? With the caveat that every individual’s an individual, what steps come next in terms of what type of practitioner to see?
DR. PRITHU METTU: That’s a good question and I think there’s not one right answer. But my approach for both types of patients is that I do think that if you do see an ophthalmologist or your optometrist and they’re concerned that you have macular degeneration, it’s a good idea to at least make an initial visit to a retina specialist because it’s someone who is trained in understanding this disease and also in giving you additional and appropriate education and counseling. He can also tell you what the latest developments and up-to-date information are, as far as research and new treatment approaches. And then, depending on your specific situation, it may be appropriate to just follow up with your regular doctor, your regular eye doctor, or to potentially follow up with the retina doctor. And then your team of doctors, if you will, can help you make that decision of what’s best for you.
MICHAEL BUCKLEY: Great. I appreciate that. That kind of leads into another question that we have. Do you have any tips or suggestions for how to make your doctor’s appointment go as well as possible?
DR. PRITHU METTU: I think one thing is making sure, as you prepare to see a doctor for the first time, that any health information or any records from your prior eye doctors that you might have seen gets transmitted to your new doctor. I think it’s helpful to actually take a copy in hand as a backup just in case wires get crossed and things don’t come through in the mail or email. Secondly, I think it’s a good idea to make a list of questions that might come up, so that way you’re not scrambling to think about things off of the top of your head while you’re with the doctor. I think those are really the main two things. And the third is just maybe to keep in mind that going to see a retina doctor is very different from most eye doctors, because you’re kind of getting sometimes two or three visits in one. You’re getting imaging tests and you’re getting an examination and sometimes treatment—and so just understanding ahead of time what all is going to happen so you can plan accordingly for your time.
MICHAEL BUCKLEY: We have a couple of questions that have come in about things that we haven’t talked too much about in the past. I was wondering—one caller from New York wonders, is there a relationship between cholesterol and AMD?
DR. PRITHU METTU: That’s a great question. There is pretty compelling science that suggests that there may be some overlap in the biology of high cholesterol as it relates to heart disease and as it might relate to macular degeneration. One theory for how macular degeneration develops is that you get a buildup of abnormal fats—animal fats—underneath the retina and that either serves as a source of injury to the retinal tissue or that it serves as a barrier that prevents normal exchange of nutrients and wastes from those retinal cells. There are efforts to understand more about those pathways and to develop therapies directed at lipid fat metabolism and lipid metabolism that may overlap with the biology of cholesterol.
MICHAEL BUCKLEY: Thank you. The next question involves a word that I’m not sure I’m going to pronounce right. Does the loss of the vitiligo pigment of the skin have anything to do with AMD?
DR. PRITHU METTU: I think that’s vitiligous pigment or vitiligo?
MICHAEL BUCKLEY: Yeah.
DR. PRITHU METTU: To my knowledge, no. I think that thus far there does not appear to be an overlap with the skin pigmentation and age-related macular degeneration.
MICHAEL BUCKLEY: We have time for a couple of more questions. You’re calling us today from the Carolinas, and we seem to have an awful lot of floods and hurricanes and forest fires out West and everything. In terms of someone that has some vision health issues that they’re working with a doctor on, are there best practices for preparing for some type of natural disaster—the possibility of evacuating when they’re on daily medication or have some type of vision challenges? I was just wondering if you have thoughts about that?
DR. PRITHU METTU: Yeah, a great question, and I think that that is especially a concern for folks who do live in areas that are vulnerable to adverse weather or environmental conditions. I think it’s a good idea to really be prepared for that, and one of the key things is good personal record-keeping—keeping a list of all of your specific health issues and doctors and a list of all of your medications. If you’re someone who, for example, has wet macular degeneration, keeping a list of your history of treatments and when you had a treatment last and what the current plan is for treatment in case, for whatever reason, you have to relocate or evacuate to another area. You’ll have all of that information ready at your fingertips, and that’s one less thing that will add a layer of stress to your day-to-day. The last thing is, as you think about where you may evacuate to and the off-chance that you may need temporary housing or be away from home for a while, that you identify a potential doctor whom you might be able to see in that event. And the last part, obviously, if that threat is much more real. I think that these things are good to keep in mind in that setting.
MICHAEL BUCKLEY: Thank you. I think it’s an increasing reality, and the ideas that you suggest would help a lot of the stress levels during a difficult time. At the very outset of today’s conversation, you mentioned that you’re involved with clinical trials, and I was wondering if you could tell us some questions that people should ask their doctor about clinical trials when that topic is broached in an office visit. Any suggestions for what the patient should be asking about or thinking about?
DR. PRITHU METTU: That’s a really good question. I think clinical trials are really a fantastic resource in a number of ways. Obviously, it’s the way that we find out whether a drug could potentially be effective for patients and become more widely available to patients if they’re in need of health care.
For patients, particularly those who may be seriously afflicted with these diseases, it offers them potential hope that one of these drugs might work for them. The key underlying all of this is making sure that the trial is a good fit for them, and some of that is their disease. What is it about their disease that might make them a good candidate for the trial? What is realistic in terms of expectations?
Now, these trials are investigational, meaning that we’re learning about the drugs, and we think they could be effective, but we’re not sure. But assuming that they are effective, what is reasonable? What could one potentially expect? And then lastly, what’s the responsibility and requirements of the individual patient and their family? Some trials can be very involved. There are some trials that last 2 or 3 years and require monthly visits throughout that time. And other trials are kind of short, and knowing what’s expected and what the commitment is, I think, will help patients decide if it’s the right choice for them.
MICHAEL BUCKLEY: Just a couple more quick questions. Dr. Mettu, we have a caller from Texas who’s asking, do you have knowledge or an opinion of something called a ForeseeHomemonitoring system? Is that something that you could discuss for a minute?
DR. PRITHU METTU: Yes, I’m familiar with it. The ForeseeHome monitoring device, to my knowledge, is the first device or technology that’s been approved by the FDA for home monitoring and detecting conversions from dry macular degeneration to wet macular degeneration. What makes this a very useful tool in our toolbox, so to speak, is that it’s trying to detect wet macular degeneration at the earliest possible time, even before symptoms might be noticed by the patient. And that’s important because the studies have shown that the best predictor of vision for patients who have wet macular degeneration is the vision at the time of diagnosis. So we can detect the disease when the vision is good and start treatment and maintain good vision. That’s easier than trying to reverse it when the vision is gone or when the vision has gotten worse. In that respect, I think it has the potential to improve patient outcomes.
It’s basically a gadget that will sit on your countertop. You peer into it. It’s mapping out the lumps and bumps in the back of the eye. It tries to detect if a new lump or bump forms that could be a new blood vessel, and then if there is something that’s concerning, it sends an alert to a monitoring system, which then gets communicated to the doctor. And then there’s an opportunity to be checked out to see if there’s concern for a possible new blood vessel that would signify wet macular degeneration. I do think it’s a useful tool and it’s worth discussing with your doctor to see if that would be appropriate for the individual patient.
MICHAEL BUCKLEY: Thank you. Just a quick follow up to that. Do you know if that tends to be covered by Medicare or private insurance?
DR. PRITHU METTU: I can tell you that some of those decisions are made regionally, based upon the decision of the local Medicare contractor. But at least here in the Southeast, it has recently been approved to be covered by Medicare. There may be a copay or some financial responsibility for the patient, but the model is kind of a monthly subscription to these. So in areas where it is covered, Medicare pays a certain amount on behalf of the patient, and there may be a small monthly copay that the patient or their supplemental insurance has to cover.
MICHAEL BUCKLEY: Thank you. And again, if any of our listeners are interested in any of the materials that we mentioned on this Chat today, we have a new publication called Understanding Macular Degeneration. We have our clinical trials guide, and Questions to Ask Your Eye Doctor, and the AREDS vitamin supplement is listed in our publication Macular Degeneration: Essential Facts.
We’ll also post a written transcript and an audio file of today’s Chat on our website, BrightFocus.org, which will be up in about 2 weeks. Our next Chat will be on Halloween, October 31st. We’ll get a chance to expand on some of the topics Dr. Mettu mentioned today about new drugs that are at different stages of the development process. It will be a great chance to learn about some promising opportunities.
Dr. Mettu, you’ve been really helpful and you addressed a wide range of issues very clearly, and we really appreciate that. I was wondering if we can conclude today by asking, do you find that working with your patients there’s a common misperception or common myth, or something that you frequently need to address with your patients?
DR. PRITHU METTU: That’s a good question. I think probably that there’s not necessarily one thing that I see often, but I’ll try to pick one, perhaps. I think for patients with dry macular degeneration, there’s oftentimes I’ve thought well, there’s not really any drugs or treatments, there’s nothing I can do. On the one hand, it is true that there aren’t any FDA-approved treatments. But I do think being plugged into the health care system—both by seeing your eye doctor and, in some cases, for folks who have advanced disease, being plugged in with vision clinics and vision rehab and also appropriate patient and family support groups—I think that there are issues that often relate to our day-to-day lives and how we function that can be practically addressed in the way of vision aids or occupational therapy strategies, to improve the living environment to optimize function. And then also, to have a network of support to sort of help to cope with some of the challenges that arise from these vision impairments. So while we all want to see our efforts move forward to try to identify drugs that are going to help reverse vision loss and improve vision for these patients, I think it’s important that we look at the whole picture of the patient and their families to try to help support them in the best way possible.
MICHAEL BUCKLEY: Well, that’s great, and I think it puts it in a broader perspective. So again, Dr. Mettu, I just want to thank you so much for being so generous with your time and so helpful to all of us. And to our audience, we appreciate you joining us again and asking a lot of great questions again. The questions we didn’t get to today, we hold onto them and try to get them asked in future Chats or addressed in some fashion.
On behalf of the BrightFocus Foundation, I just want to thank Dr. Mettu, I want to thank all of the listeners, and we hope that you’ll be back on October 31st for our next BrightFocus Chat. Dr. Mettu, thank you very much.
DR. PRITHU METTU: Thanks for having me.
MICHAEL BUCKLEY: It was our pleasure, and on behalf of the BrightFocus Foundation, this concludes today’s Chat. Thank you.
BrightFocus Foundation: (800) 437-2423 or visit us at www.BrightFocus.org. Available resources include—
* UPDATE: In October of 2019, the FDA approved BEOVU® (brolucizumab). Learn more about this treatment.