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Answering Your Questions about AMD (September 2016)

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Dr. Joshua Dunaief

University of Pennsylvania’s Perelman School of Medicine

The telephone discussion features Dr. Joshua Dunaief, of the University of Pennsylvania’s Perelman School of Medicine, who specializes in the study of age-related macular degeneration.

  • BrightFocus Foundation
    All Your Questions Answered About AMD
    September 28, 2016
    Transcript of Teleconference with Joshua Dunaief, MD, PhD
    1:00–2:00 pm EDT

    Please note: This Chat was edited for clarity and brevity.

    MICHAEL BUCKLEY: Hello, I am Michael Buckley with BrightFocus Foundation. Welcome to today’s BrightFocus Chat, “All Your Questions Answered About AMD.” We would like to welcome our speaker today, Dr. Joshua Dunaief. Dr. Dunaief is an Assistant Professor in the Department of Ophthalmology at the University of Pennsylvania Perelman School of Medicine. Dr. Dunaief also regularly contributes as an author to our macular degeneration Insights articles, which discuss various aspects of age-related macular degeneration (AMD).

    If today is your first time joining us, welcome to the BrightFocus Chat and thank you. Let me take a moment to tell you a little bit about BrightFocus and what we will do today. BrightFocus funds some of the top scientists in the world. We support research that is trying to find cures for macular degeneration, glaucoma, and Alzheimer’s. We share the latest news from these scientists with families that are impacted by these diseases. We have a number of free publications and plenty of materials on our website, We also have information on every research grant that we fund, if you are interested in learning more about our scientists and their work. BrightFocus Chats, like the one today, are another way of sharing information from the world of research with families that are impacted by macular degeneration.

    During each Chat, we give you the opportunity to submit questions. We don’t always have the opportunity to answer all of them on each Chat, but rest assured that we do save them for use during future Chats. What we are going to do today is go back and answer some of the previous questions along with many new ones you submitted by email and on our website.

    Now let’s turn to Dr. Dunaief. Thank you for joining us today.

    DR. DUNAIEF: It is my pleasure, Michael. It is great to be able to reach so many people at once and answer their questions. Also, let me congratulate you on pronouncing my name correctly. That is unusual.

    MICHAEL BUCKLEY: Thank you! Before we get started, can you tell us a little bit about your professional background and experience?

    DR. DUNAIEF: I am an ophthalmologist and a macular degeneration specialist. I’ve treated thousands of patients with macular degeneration and done thousands of injections. I do research on the causes of macular degeneration—trying to develop new treatments for the disease.

    MICHAEL BUCKLEY: That is great. I know that expertise will be very helpful to our listeners and all those with questions. I would like to start with a few questions that we get asked very frequently about treatment for wet AMD. First question comes from Gloria in California. Her doctor suggested that she may soon be able to stop the injections, which she has been taking for 6 years. She says she will ask her doctor more questions, but she wanted to know what you have to say about the possibility of stopping injections.

    DR. DUNAIEF: That is a really good—and common—question. Different people need different injection frequencies. Some patients need injections every 4 weeks, and some can do very well with injections less frequently. The same is true for the duration of the therapy. Some people can be weaned off of the therapy over time, and other people need to continue the therapy for many years. The only way to determine that for each patient is to follow up and do optical coherence tomography (OCT) imaging and exams and see when the leakage continues—blood vessel leakage—and when it stops. If it stopped for a while, some ophthalmologists will stop doing injections and just follow the patient and try to do fewer injections over time. Eventually, some patients can stop the injections, but they do need to keep following up to make sure that the leakage doesn’t restart.

    MICHAEL BUCKLEY: We have a related question from Linda in Maryland, who has been receiving Lucentis shots every 5 to 6 weeks and says her eyesight has not improved, but it is getting worse. Would you give similar advice to someone in that situation?

    DR. DUNAIEF: Well, many people do experience an improvement in vision after the injections start, but some people just have a stabilization, and an unfortunate minority still lose vision even in the short term. What we do for the patients who continue to lose vision is inject as frequently as we can, which is every 4 weeks, and sometimes we will change medicines. There are three medicines that are used right now that all target the same proteins, VEGF or Vascular Endothelial Growth Factor. We call these anti-VEGF medicines. There is Lucentis, Avastin, and Eylea. It is possible that even though all of these drugs target VEGF, one drug may work better for certain patients and another may work better for other patients. Sometimes we will switch medicines and see if that can help somebody who is not seeing an improvement in their vision.

    MICHAEL BUCKLEY: Thank you. We have a few more questions about injections. We can all understand why this is a very important topic. Richard from Ohio is wondering, “Do injections for macular degeneration kill retina cells and cause atrophy?”

    DR. DUNAIEF: That is a really good question. VEGF does cause blood vessel growth and leakage, which is bad, but it also can support normal cells in the retina. At least in theory, inhibiting VEGF over the long term could cause some loss of retinal cells. Now, clinical studies have shown that over 5 to 7 years, patients who are getting injections do tend to lose a little bit of vision over time. A lot less than they would have lost if they hadn’t been receiving the injections, but they do tend to lose just a little bit—a few letters, a line of vision—over the years. That may be due to some atrophy of some of the retinal cells.

    MICHAEL BUCKLEY: A minute ago you mentioned VEGF, and Bonnie from Washington State is asking if elevated VEGF can be noted in a blood test and if there is a correlation with blood vessel issues and wet macular degeneration. Could you tell us a little bit more about elevated VEGF and what is related to that?

    DR. DUNAIEF: The important issue with VEGF is that its levels are increased in the retina. The levels of blood are not thought to play an important role in the damage that VEGF can do in the retina. It is really just the VEGF production by the retina that is important. A few studies that have measured blood VEGF levels and the risk of wet macular degeneration have really not shown a correlation between blood VEGF and macular degeneration risk. It is really just the retinal and intraocular VEGF that we need to look at and target with these anti-VEGF medicines.

    MICHAEL BUCKLEY: Thank you. Just to pause for a moment for a little bit of housekeeping. I know Dr. Dunaief is giving us a lot of excellent advice today, and I want to remind folks that the transcript of today’s session will be available free of charge at That can help serve as a refresher for a lot of the good advice he is giving today. BrightFocus also provides a great publication free of charge, and that is called “Macular Degeneration Essential Facts.” It addresses a lot of the topics for today. I encourage you to contact us, and free of charge you can get “Macular Degeneration Essential Facts” as well as the transcript of today’s Chat to reinforce the advice from today.

    Another question that we hear from Chat participants—Carmen from Florida says that her retina specialist says there is nothing that can be done for her left eye, which has wet AMD. Carmen is wondering, is this something that she should seek a second opinion about? Or should she accept that there is probably nothing else to be done? Could you comment on that?

    DR. DUNAIEF: There are, unfortunately, some patients who have severe enough damage to the macula that further anti-VEGF injections are not helpful, and those patients may have had their wet macular degeneration start before the anti-VEGF drugs became available and then developed a lot of scarring in the retina, which is irreversible. It is possible that she wouldn’t benefit, but it certainly wouldn’t hurt to get another opinion and see if another doctor might think that she could benefit.

    MICHAEL BUCKLEY: Sometimes getting a second opinion can be a little bit of an awkward experience for families. Do you have any advice on how someone should go about getting a second opinion?

    DR. DUNAIEF: Yes, it certainly can be awkward. It is kind of implying that, maybe you don’t trust the doctor that you are seeing initially. But it really shouldn’t be taken that way. Certainly a second opinion can be helpful. Not all doctors think the same way about everything. If the patient is uncomfortable telling the first doctor that they are going to get a second opinion, they don’t have to tell them. They can just go ahead and get an opinion from another doctor. It is helpful though, when getting a second opinion, to obtain the medical records. Especially the images, the pictures of the retina that have been taken over the years. What you could do if you want to get a second opinion is just request a disc, CD, or printout with the images so that you can just take them to the second doctor to get the second opinion. That is actually a lot more effective than asking the first doctor to send the images to the second doctor because those things can get lost in the mail. It is best to just have a copy of your own images that you can just walk in with and show them to the second doctor.

    MICHAEL BUCKLEY: Great. Thank you. That is very helpful advice for people who sometimes feel a little awkward or overwhelmed about the best process. I would like to turn to dry AMD. One of the questions we hear a lot about is something called the AREDS supplements and other questions like that. Dr. Dunaief, we have several people who have sent in related questions about AREDS. I was wondering if—before we turn to those, if you could first explain what AREDS is and why it is so important, and then we can turn to some of the specific questions. Can you take a moment to tell us a little bit about AREDS?

    DR. DUNAIEF: Sure. AREDS stands for Age-Related Eye Disease Study, which was a study funded by a branch of the NIH called the National Eye Institute. What they did is they took 3,000 patients with AMD at various stages and gave them either antioxidant vitamins or a placebo and followed them over 6 years. Amazingly, the patients who got the antioxidant vitamins had a 25 percent reduction in the risk of progressing to advanced macular degeneration. That really indicated that people with what we call intermediate macular degeneration should be taking these antioxidant vitamins. So what do I mean by intermediate macular degeneration? That is defined by a certain number of little white spots in the retina that can be detected with photographs or with an eye exam. Those little spots are called drusen. Drusen is a German word that means pebble—so it is like having little tiny pebbles underneath the retina. Those drusen are an indicator of the risk for potential vision loss in the future. The more drusen, the larger the drusen, the higher the risk.

    What was found in this study is that patients with enough drusen to have some risk for vision loss or progression to advanced macular degeneration over the next 5 years did benefit from the vitamins. A lot of times patients will ask me, “Well, I only have a few drusen and they are small, should I take these vitamins?” The answer is no, because we don’t have any evidence that over the many years that would take for such a person to actually develop vision loss, at least on average, it is not known whether the vitamins would be helpful or even perhaps a little risky if they had to be taken for several decades.

    Many people ask me about vitamin C, and in the AREDS studies there was really no indication of any problem with the vitamins except for a very slight increase in urinary-related hospitalizations for men—about a 1 percent increase of that. There have been two AREDS studies. They are called AREDS 1 and AREDS 2. In AREDS 2, what was modified is an antioxidant call lutein was used instead of a different antioxidant called beta-carotene. The lutein is safer because beta-carotene can lead to lung cancer in current smokers or probably even people who have smoked in the past. The AREDS 2 formula is what is currently recommended.

    Let me tell you what is in AREDS 2. It is 10 milligrams of lutein, which is used in combination with a related antioxidant called zeaxanthin, which is given at 2 milligrams. There is vitamin C at 500 milligrams, vitamin E at 400 international units, zinc oxide at 80 milligrams, and cupric oxide at 2 milligrams. That is the dose that you should be taking each day. [See AREDS chart, in resources at the end of this transcript.] The pills are recommended to be taken in the morning and the evening. Each pill has half the levels of what I just cited. By taking two a day you get to that full level that I just mentioned.

    MICHAEL BUCKLEY: Great. Thank you very much. For our listeners, Dr. Dunaief just gave some very helpful information. I want to remind people that we will have a full transcript of this Chat available at and also the publication we mentioned a few minutes ago, “Macular Degeneration Essential Facts,” which outlines the specifics about AREDS. Dr. Dunaief, I want to run through three or four different questions about AREDS. You briefly talked about time of day for taking these pills. Janette from New York is wondering if there is a better time of day. I know you said morning and evening. Are there some people that would or should just do once a day? Or do you recommend everyone do morning and evening?

    DR. DUNAIEF: Based on the studies, I recommend that everybody with intermediate or advanced AMD take two a day—one in the morning and one in the evening. We don’t know of any particular timing that is better or worse other than morning and evening. Just take them whenever is convenient in the morning and then another one whenever is convenient in the evening. It is recommended to take it with a fair amount of water, a glass of water.

    MICHAEL BUCKLEY: That is really helpful. One of the components you mentioned of AREDS is zinc, and Janette is also wondering if it is possible that AREDS could contain too much zinc? Are there risks with too much zinc?

    DR. DUNAIEF: Not at the level in the AREDS formula. There is no evidence from the AREDS study or from the preponderance of other studies in the medical literature about zinc that the level in the formula—80 milligrams of zinc oxide—is harmful. I should mention that there are other forms of zinc that you can buy in a health food store, but the form is important. It is important to use zinc oxide because that is the form that was studied in AREDS and that is the form that is known to be protective. The other forms are absorbed differently, so you actually will be getting a different amount of zinc in your body if you take a different form of zinc, like zinc gluconate. So you do want to take the form zinc oxide. I also want to mention that in the AREDS 2 study, they looked at whether it might be okay to reduce the amount of zinc, and actually zinc oxide 25 milligrams was equally as effective to zinc oxide 80 milligrams. If you are concerned about taking too much zinc, I think taking zinc oxide 25 milligrams per day would be acceptable, and I think that certain forms of the AREDS 2 vitamins that you can buy over the counter have the lower dose of zinc if you are concerned about toxicity.

    Another interesting thing about zinc is that the patients who took zinc in the AREDS study actually lived longer. It is possible that there is a systemic benefit throughout your whole body to taking zinc.

    MICHAEL BUCKLEY: I am glad you mentioned the distinction between 25 milligrams and 80. We had a very attentive listener submit a question as you were speaking about how she has sometimes heard 25 and other times has heard 80. I appreciate you clearing that up. Melanie from Michigan has a question that crosses many peoples’ minds. She is concerned about the cost of name brand AREDS being too expensive. She is wondering, “Are there pharmacy brands that are equally as effective?” Does the brand itself matter? Is there a benefit that would make that cost worthwhile?

    DR. DUNAIEF: Well, actually, it does matter because vitamins are not regulated as rigorously as drugs, and the National Eye Institute actually looked at some of the vitamins on the market and did biochemical analysis of the ingredients to see if the pills actually contained the things that are on the label in the amounts that are on the label. Many of them did not. There were actually only two brands that had accurate labeling. One was PreserVision from Bausch + Lomb and the other was ICAPS. I should say I have absolutely no financial interest in either of those companies, so I am just reporting the results of the analysis with no bias.

    MICHAEL BUCKLEY: I appreciate that. A related question from Eileen. She is having trouble finding the AREDS formula and wants to know if you cannot find one of the ingredients in AREDS, can you buy other supplements and make up the difference, such as vitamin C.

    DR. DUNAIEF: You could try to put the ingredients together yourself, but you would be taking more pills, and you would be running the risk that the particular brand that you are using doesn’t actually have the amounts that are advertised on the label. What you need to do is just look for vitamins that are listed as following the AREDS 2 formula, which contains the micronutrients that I went through before at the levels that I went through before. You can get them at many drug stores. You can get them online, if you just search AREDS 2 vitamins.

    MICHAEL BUCKLEY: If you don’t mind, we have a few more questions about AREDS. This is really stirring up a lot of good questions today. Jacklyn is wondering, “Does AREDS help with wet AMD?”

    DR. DUNAIEF: AREDS reduces the risk of progression to wet AMD. For somebody who has intermediate AMD, which is just drusen—fairly large—but not yet wet AMD, AREDS reduces the risk of progression of developing wet AMD. For somebody who has wet AMD in one eye and no wet AMD in the other eye, just drusen, then the AREDS will reduce the risk of developing wet AMD in the eye that does not yet have it. For patients who already have wet AMD in both eyes, it is unknown whether taking AREDS vitamins will be helpful.

    MICHAEL BUCKLEY: That is very helpful. Related to that, Eloise has a question. She has a history of macular degeneration in her family. Right now she is taking AREDS. She is wondering if there should be any type of home monitoring of her vision that she should be doing while taking AREDS.

    DR. DUNAIEF: Eloise, if you don’t have drusen to the level of intermediate AMD, then I actually don’t recommend that you take AREDS vitamins just because you have a family history. Again, your risk of developing AMD over the next decade or two may not be high enough to justify the risk of taking AREDS vitamins for 20 years. We know that AREDS vitamins are safe for 6 years, but we don’t know if they would be safe for 20 years. So, just having AMD in the family is not enough of a reason to take it.

    What you should do is things that can reduce your risk of AMD without increasing any kind of systemic risk. Those things are to not smoke—or to quit if you currently smoke— and to wear sunglasses when you are out in bright light, when you are driving, if you are out in the snow or out on the water. There is some evidence that long-term exposure to bright light may increase the risk of AMD. Being overweight is associated with AMD risk, especially abdominal fat. So decreasing that abdominal size—hard as I know it is—can probably decrease the risk. Also, having an annual eye exam to see if you have any drusen, which would help you know what your risk might be going forward.

    You asked about home monitoring, and that is very important. If you notice a change in your central vision, then it is important to go and see your ophthalmologist for a dilated eye exam. It is important to do that home monitoring, covering one eye at a time. If you have lost some vision in one eye, the other eye will compensate, and you might not notice it for even months. So cover one eye at a time and look at a page with print on it, a magazine, a newspaper, and just make sure that you can read it with each eye—that the letters look clear.

    There is something called an Amsler grid, which is basically a piece of graph paper. What you do with that is with your reading glasses on, you look at the dot right in the center. If you see any missing or wavy lines, that can be an indication that you have developed wet AMD and should have that dilated eye exam. I recommend screening at home with that Amsler grid. You can just put it on your refrigerator and just look at it once a week. If you notice missing or wavy lines or a change from what you saw in the past, that is a good time to call your ophthalmologist and make an appointment.

    MICHAEL BUCKLEY: I am glad you mentioned that. To our listeners, BrightFocus provides the Amsler grid free of charge. They are magnetic, and you can put those on your refrigerator or on the side of a counter or cabinet in your home—somewhere you will see it regularly. You can stay on the line at the end of this call and give us your name and address. We have one more question about AREDS. Jacklyn is wondering, “Is there a risk to taking AREDS and also taking a multivitamin along with it?”

    DR. DUNAIEF: Good question. Probably not. It depends which multivitamin. The AREDS ingredients are at about 5 to 10 times the U.S. recommended daily allowance (USRDA) for those ingredients. So the multivitamins are typically at 1 time the USRDA. Taking a multivitamin in addition to AREDS, for most multivitamins, isn’t going to increase the dose of the AREDS micronutrients by very much. I know that Centrum Silver will not increase the dose of any of those significantly. In fact, about two-thirds of the people in the AREDS trial were taking Centrum Silver in addition to the AREDS vitamins. If you use something other than Centrum Silver, just look at the ingredients listed on the vitamin bottle for the multivitamin and make sure that none of the AREDS micronutrients are listed at a level any higher than 100 percent of the U.S. recommended daily allowance.

    MICHAEL BUCKLEY: We have had a couple of questions come in about cataract surgery. Several of your listeners have wondered if cataract surgery would increase one’s risk for AMD or maybe make your AMD more severe. Do you have thoughts on that?

    DR. DUNAIEF: That is a really good question. There have been several studies on that, some of them quite large. The largest have shown that there is no increased risk for macular degeneration in people who have cataract surgery. If you need cataract surgery and you have macular degeneration, you can go ahead and have the surgery. It is not always so simple to determine, however, whether cataract surgery would benefit somebody with macular degeneration. Because if you can’t see well and you have both macular degeneration and a cataract, it could be because of the macular degeneration, it could be because of the cataract, or it could be a combination. An ophthalmologist can really help you determine how significant the cataract is in the decreased vision by evaluating the condition of the retina and evaluating the opacity of the lens and measuring those two against each other.

    There is also a device that can shine a tiny little eye chart through a cataract. It is called the potential acuity meter or PAM. For many cataracts, that can help determine what the vision would be like if the cataract weren’t there. In other words, it helps to evaluate the condition of the retina, and if the retina is healthy enough, then removing the cataract could actually lead to a significant improvement in the vision.

    MICHAEL BUCKLEY: We still have a few minutes remaining. Dr. Dunaief, we know you are a very well-regarded researcher on the science involved in understanding AMD and possible treatments. We have a few questions related to that. Susan from Missouri wonders if there are any promising clinical trials for wet and dry AMD. Big picture, what is your prognosis for the field of research and possibly improving medical care around AMD?

    DR. DUNAIEF: I am very optimistic that new treatments will be coming soon and that they will lead to better outcomes with less frequent injections. There is a lot of research being done at both the basic level, to try to understand the disease better, and also at the clinical trial level.

    The two things that are most advanced in clinical trials right now are a drug called Fovista, which is injected into the eye like the anti-VEGF’s, but it is targeted differently from VEGF. It is called PDGF for platelet-derived growth factor. PDGF promotes the stabilization of new blood vessels, which is bad because you want those new blood vessels that are leaking and bleeding in the retina to go away. So targeting combinations of VEGF and PDGF led to better vision outcomes in a phase II clinical trial.

    We are currently nearing the end of phase III clinical trials for Fovista and if they are favorable, I think that we may see Fovista on the market in about a year or two. That may lead to not only improved vision outcomes, but also possibly less frequent injections. We will need to see how the trials pan out and how it works in clinical use over the first few years.

    For dry AMD, the advanced form of dry AMD is called geographic atrophy, so patients with that condition have not only the drusen, but they also have lost some vision cells in the center of the retina, in the macula. There is evidence that inflammation plays a role in that form of macular degeneration. Actually, in the wet form too. Specifically, an arm of the immune system called the complement cascade can promote the loss of those cells. There is a trial that is ongoing now with a complement inhibitor that can be injected into the eye, the same way anti-VEGF drugs are injected, and they are looking at whether those treatments can slow the progression of the atrophy. In other words, to try to keep the vision where it is instead of having a blind spot in the central vision enlarge gradually over time. I think we may see that in about a year or two if the clinical trial is successful.

    MICHAEL BUCKLEY: Those are some really exciting updates from the field of research. When you mentioned clinical trials and how important those are, I think we all know and hear so much about clinical trials, and some people have concerns. To that end, BrightFocus recently put out a free publication called “Clinical Trials: Your Questions Answered.” Obviously, in the end that decision is between you, your family, and your physician, but the new publication gives you some things to consider and questions to ask. Just like with the Amsler grid and Macular Degeneration Essential Facts, our new clinical trials publication is available free of charge. You can call BrightFocus at any time to ask for this clinical trials publication.

    We appreciate the updates from the field of research. We get a lot of questions about whether eye drops and pills will ever replace injections. It is really helpful to hear some of that research.

    We are getting to the end of our time together. I would like to conclude by thanking Dr. Dunaief for fielding so many questions today. Your answers were outstanding, and I think everybody who has been a part of the Chat today has certainly learned quite a bit. As mentioned, we will have a transcript of this Chat available online. You can also listen to this Chat and past Chats in an audio form on iTunes and SoundCloud.

    I also want to mention that Dr. Dunaief has been kind enough to write many helpful articles for about macular degeneration, including about the trial drug Fovista that he mentioned a minute ago.

    Dr. Dunaief, on behalf of everyone at BrightFocus and everyone on the Chat today, thank you. You have been extremely helpful. I found you to be very clear and easy to follow. You have given a lot of people a little more knowledge and peace of mind.

    DR. DUNAIEF: It was my pleasure, Michael—a lot of great questions. Just a little bit more information to digest—please remember to eat a healthy diet that includes lots of fruits and vegetables and fatty fish twice per week, like salmon or sardines. Those things have also been shown to decrease the risk of vision loss.

    MICHAEL BUCKLEY: Great advice. From all of us again, I appreciate you being so generous with your time and your experiences. This concludes today’s BrightFocus Chat. I want to thank everyone who joined in and asked some great questions. If we were not able to answer your question, we will try to follow up with you and provide some answers. Thank you very much.

    Here is the AREDS2 recommendation for a supplement formula that may delay the progression of intermediate dry AMD to the more advanced stage. Look for the AREDS2 formula on the packaging of over-the-counter supplements.


    500 mg of vitamin C
    400 IUs of vitamin E
    10 mg of lutein
    2 mg of zeaxanthin
    80 mg of zinc oxide
    2 mg of copper as cupric oxide

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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 therapy.

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