Milam A. Brantley, MD, PhD
Milam A. Brantley, MD, PhD, of the Vanderbilt Eye Institute, answers questions about macular degeneration, a leading cause of vision loss in Americans 60 years of age and older.
Milam A. Brantley, MD, PhD, of the Vanderbilt Eye Institute, answers questions about macular degeneration, a leading cause of vision loss in Americans 60 years of age and older.
Macular Degeneration: Your Questions Answered
July 26, 2017
Transcript of Teleconference with Dr. Milam Brantley
1:00–2:00 pm EDT
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 am Michael Buckley from BrightFocus Foundation. Welcome to today’s BrightFocus Chat.
If today is your first time on a BrightFocus Chat, let me tell you a little bit about BrightFocus and what we will do today. BrightFocus Foundation funds some of the top researchers in the world. We support scientists trying to find cures for macular degeneration, glaucoma, and Alzheimer’s. We share the latest news from these scientists with families who are impacted by these diseases. We have a number of free publications and plenty of materials on our website, www.BrightFocus.org, that offer tips for living with diseases like macular degeneration. BrightFocus Chats are another way of sharing this information.
Today’s BrightFocus Chat is “Macular Degeneration: Your Questions Answered.” We are doing this today because we’ve been very fortunate to get a high number of questions during our BrightFocus Chats, and unfortunately we are not able to answer all of them in that time. We thought that periodically we would go back and ask some of the questions that we didn’t have time to answer in previous Chats. Today we are really lucky to have these questions answered by one of the top researchers in the field of macular degeneration, Dr. Milam Brantley at Vanderbilt University.
Dr. Brantley, you’ve been very generous with your time in previous Chats, and we are thrilled to have you here. I was wondering if you could start off for a minute or two with basics about macular degeneration, in case we have folks who are new to the disease or maybe checking in for the first time on behalf of family members. I was wondering if you could give a brief overview of the disease and some of the current treatments.
DR. BRANTLEY: Sure. Thank you, Michael, I really appreciate the invitation to participate today.
Most of your listeners are going to be familiar with macular degeneration or AMD, but many of the terms or words that patients have heard about are things like dry or wet AMD. AMD affects, as its name mentions, the macula, which is a part of the retina or underpart of the eye, and that is where our central vision comes from. AMD typically only affects central vision. When we hear about dry AMD, we usually think of the early forms of macular degeneration, which involves small deposits right underneath the retina. We can see the small deposits when we look in the back of the eye, usually yellow in color, called drusen.
Drusen mark early or even intermediate AMD. Early or intermediate AMD usually does not affect vision at all. One might not even know they have it until the back of the eye is looked at. Another category is advanced AMD, which comes in two types. One is wet AMD, which doesn’t mean it is actually wet but rather that there is fluid, or sometimes blood, within or underneath the retina. Wet AMD is caused from abnormal blood vessels that grow under the retina, and they leave that blood or fluid. Wet AMD is also known as exudative or neovascular AMD.
Another form of advanced AMD is called geographic atrophy. Atrophy just means it no longer has shape anymore, meaning there are no longer any retinal cells. The word geographic means a map, which refers to a map of the back of the eye, which also can severely affect the vision. Most of the treatments that we know about involve wet AMD, which are the injections in the eye that patients or some of their friends may get on a routine basis to treat the AMD. The only treatment available for [intermediate] AMD is ARED vitamins, which typically can help prevent progression to the advanced forms of AMD.
MICHAEL BUCKLEY: Great, thank you, I know you are one of the leading clinicians and see a number of patients on this disease. A lot of the questions today may be common questions that you get but would be great for our listeners to hear. Our listener, Elizabeth from Massachusetts, has a question about being out in the sun. She played outdoors a lot and is wondering if those years were a risk factor for AMD.
DR. BRANTLEY: That’s a very good question that we don’t get often. There have been a few studies that look at sunlight exposure and the risk of AMD. The bottom line is that they have been relatively inconclusive or at least have not shown a strong risk factor for life. We can only encourage patients to wear sunglasses when outside. Even if there is a small risk of light damage to the retina, wearing sunglasses can prevent light damage. However, when the larger studies were done on people who were fisherman in the Chesapeake Bay they didn’t find much of a difference in people who were exposed to light versus people who weren’t exposed to light. Regardless of that, wearing sunglasses outside is a pretty good idea.
MICHAEL BUCKLEY: Great, let’s stay on the sunglasses topic for a minute. When you go to the store and look at sunglasses they all have stickers on them proclaiming their product is the best. Do you have any general guides for people who are looking to follow your advice on wearing sunglasses more often?
DR. BRANTLEY: In general, sunglasses that have UVA and UVB protection are good. UVA and UVB can be found in the vast majority of sunglasses. That is the general rule for everyone. As you get older, more protection from the sun is needed, and those with AMD will want to wear sunglasses that will cut glare (such as amber color glasses or blue blocker glasses) and cut UVA and UVB without dimming things that can really help.
MICHAEL BUCKLEY: In your opening you talked a little bit about the treatments. We have several questions about injections for wet AMD. Bob from New Jersey asks, “Is there any danger in getting shots for wet AMD every month of a period of a lifetime as a preventive measure?” He wonders how many shots a person can receive without getting any negative effects.
DR. BRANTLEY: That is another really good question that we get all the time. I get a lot of people that come into my office and compare injection frequencies to their friends or family member and say “They get injections all the time. How come we get them every 2 months? Why is there a difference?” The real answer is that some people with AMD simply need injections more often to keep that fluid at bay. I have patients in my clinic who if I don’t give them a shot every month, they start to notice it and lose a little bit of vision, and we do a test and we can find fluid underneath the retina.
On the other hand, I have other patients in my clinic whom we will treat when they have wet AMD and get rid of all the fluid and spread out the injections for a while, and go every 6 weeks and go every 2 months and maybe even every 3 months. Those people can stay on an every 2 or 3 month schedule, which is pretty common. If we stop or they have to miss an injection for an emergency then they might see some fluid, but as long as they are getting the injection every 2 or 3 months they are just fine. Another group of patients have their fluid under control when they go a longer time from getting injections by getting injected every 6 months (for instance, when they miss an injection but feel they are doing great). We don’t necessarily start things up again but just watch them very closely. The big trick here is different people need different amounts of the injections, and doctors try really hard to tailor that treatment for the individual patient. My goal in general is that if we can accomplish the exact same vision and accomplish getting rid of the fluid and keeping it at bay with fewer injections, I am all for that. That means the patient has to come in fewer times to the office, so I try to increase the time between injections. Sometimes it works and sometimes it does not. That is called a “treat and try” to extend the time between injects or a “treat and extend.” Again, I will reiterate, different people need different amounts of injections. There is a theoretical risk that the more procedures, the more times you have injections, perhaps the retina can thin out over time. That is hard to measure because that is part of the disease too, if doctors look at patients and notice, for instance, that they have been treating them for 4 years every month and now their retina seems like it’s thinned out a bit. But if they hadn’t treated them at all, maybe that same thing would have occurred.
My mantra is give the fewest number of injections that can keep things well controlled, and that is indeed different for different people. So comparing your treatment to your friends’ or family is hard, as each treatment is different.
MICHAEL BUCKLEY: That is good advice, to have that one-on-one conversation with your physician and in that vein of hearing that your friends’ and family’s treatments may be different.
We have heard a question that sometimes an injection for wet AMD can cause someone to have double vision as a side effect. Do you have any comments on that?
DR. BRANTLEY: That is a pretty specific question and a pretty specific symptom. Double vision, when described by patients, is typically something that involves the two eyes not lining up well. There are times— which may sound counterintuitive—but there are times that vision in one eye is just really bad, and they are only seeing out of the other eye. So they are only seeing one image, then they get treated with the injection and it clears the fluid a bit, and they have then a blurry image of the other eye. If they have an underlying condition where their eyes do not line up perfectly unless they are able to see with both eyes, that one eye can drift away now because of the injections, making their vision better. They’re actually seeing two copies of something, whereas before they were just seeing the one image from the one good eye. That is pretty unusual.
Sometimes people describe double vision and what they really mean is blurry vision, and that may not necessarily be related to the injection itself but the disease causing it to warp and look blurry. One eye may look one way and the other another way, and your brain simply cannot put those two things together. It is pretty rare to have double vision as a result of the injection, but it is not super rare to have some feeling of double vision with AMD.
MICHAEL BUCKLEY: As we mentioned in the introduction, you are one of the leading researchers in the world on macular degeneration. We had a few questions about the state of research—what is the current state? For example, one caller wonders how far away science is from stem cells being able to regrow the retina.
DR. BRANTLEY: That is a really great question and is probably one of the most common questions I get in the clinic today. To do a good job of answering that, let me back up and talk a bit about the different kinds of stem cells. I see patients with macular degeneration and inherited retinal conditions, such as retinitis pigmentosa and Stargardt’s macular dystrophy, and everyone wants to know about stem cells because they have heard about it on the radio, seen it on the internet or know someone who has had stem cell treatment.
So what does that mean? There are three different kinds of stem cells that are being considered or used for treatment for retina diseases such as AMD. The thing about stem cells that makes them stem cells is they have an ability to be pluripotent, which is a fancy word that if we break it down, “potent” means that it can do something, and “pluri” means it can do multiple things. So a stem cell has the ability to develop into different kinds of cells (for instance, a retina cell or a bone marrow cell, a blood cell).
Three or 4 years ago researchers took embryonic stem cells, made them like RPE cells, and injected them into the eyes to treat patients with AMD and patients with Stargardt macular degeneration. There are a very small number of people for whom it didn’t seem to cause trouble, which is the first thing you want to know in any study, and some people seemed to see a little bit better. But there is a long way to go on this and a lot more research to be done.
A second type of stem cell is called an induced pluripotent stem cell. People probably really heard about this one because this is when you hear about someone getting a skin cell taken out from their body and then converted into a different kind of cell. It is converted or induced by putting it in a culture dish and treating it with specific genes that make it act like an early cell again, and like an embryonic stem cell. So induced pluripotent stem cells, or IPFCs, are those skin cells that can be converted into cells like retinal pigment epithelium cells. This has huge potential but is still in the early stages.
Recently in Japan, an IPFC-type RPE cell was injected into someone for AMD and they did okay, and a second person, they started to have some issues, wondering if the cell had changed something. That is one of the concerns for induced cells, that maybe there can be some genetic changes that make the cell behave differently than one would expect, so they decided that they would make banks of induced cells from different people and inject them. This has great potential in the long run. These cases are attempts to make cells function like RPE cells in the eye. Also, they might have the ability to produce growth factors or molecules that help the cells that are still alive function okay.
The third type—and probably what most people have heard about—are adult stem cells, and the most common type are bone marrow–derived stem cells. Bone marrow stem cells are used to treat diseases like cancer or leukemia. That is a bad type of blood cell, so they get radiation that gets rid of all their blood cells and gets replaced with bone marrow transplant. People are now beginning to use bone marrow–derived stem cells— which normally go into blood cells—to treat eye conditions, and this is where people actually go to clinics and not so much at research institutions to get this treatment. This has been done several hundred times, and it is probably the most common type of treatment that has been done for eye diseases. Researchers are not trying to make RPE cells out of this, or eye cells, but are hoping that those stem cells can produce some sort of molecules that help the cells that are already in your eye. So this is a very different kind of thing, and again, that is probably is what is most in the newspapers recently. I can answer more specific questions about any of those types.
MICHAEL BUCKLEY: You proactively answered several of the questions that our listeners had on the study in Japan. Related to that, a lot of this work came from clinical trials. Staying on that research topic for another moment, what would you say to patients of yours that might be interested in clinical trials? How should they learn more about them? Is there a common question or concern that arises when you talk with your patients about clinical trials?
DR. BRANTLEY: I think the number one thing is to inform people about how all clinical trials are not created equal. There are some differences between what one person might call a clinical trial and what another person might call a clinical trial, and there are differences in the stringency and what is being reported in clinical trials. The BrightFocus publication is a wonderful place to start and is a great resource for people looking for a place they can go and get information that they can trust. The internet can be a good thing or a bad thing, as you can get a lot of information, but it is not always credible. Therefore, I encourage people to start with the BrightFocus publication, as it is easy to understand more about clinical trials.
Secondly, there is a website called www.ClinicalTrials.gov, which all clinical trials in the country have to be registered on. If I want to take patients on in my clinic and treat them and might have a group that I am not treating and see what the difference is, that would be considered a clinical trial that has to be registered with www.ClinicalTrials.gov. Registering it does not necessarily mean it is government approved; even though it is on the government website, it is just registered. Many clinical trials have been funded by grants from the government, which in a way is government approved.
All clinical trials that need to have any sort of human studies, have to have an approval from an institutional review board. There are some differences there: For instance, Vanderbilt University has one, and any time we conduct a study we get the approval of people who are knowledgeable outside our general field and also get input from the community to make sure everything makes sense and does not harm those involved. One of the things that is important in a randomized clinical trial where you have a treatment group and a control group is finding out the best evidence of treatment, meaning is the clinical trial treatment better than doing nothing or better than the current treatment?
Typically in a clinical trial, the results get reported, such as what percentage of patients showed improvement, what percentage of patients didn’t change much, and what percentage of patients had complications. There are other types of trials that call themselves clinical trials but have not reported that type of information; you can find these trials on that www.ClinicalTrials.gov as well. Those types may recruit a lot of people and treat them, but the insight or report is lacking. Therefore, it is really important to realize that although it may be called a clinical trial, it may not always really be a clinical trial. It is much clearer to see the information gathered in one place, like the BrightFocus publication. I would really recommend that be the first place to start.
MICHAEL BUCKLEY: I appreciate that, you made some really great distinctions there. Let us move away from research and conclude with the topic of medication and supplements. Dr. Brantley, a lot of the questions are about the supplements involved called AREDS. Could you briefly talk about AREDS?
DR. BRANTLEY: Absolutely, and this is something every person with AMD needs to understand. The Age-Related Eye Disease Study (AREDS) was a large National Eye Institute–sponsored study that was completed somewhere around the year 2000 and looked at a combination of antioxidants and zinc to see whether this combination of vitamins could slow down the progression of patients with the earlier intermediate AMD advancing onto the bad types of AMD that I mentioned earlier, the geographic atrophy or wet AMD. The original AREDS formula had vitamin C, vitamin E, beta carotene, and zinc, and a little copper to offset the zinc. The results basically were that over a 5-year period it actually reduced the chance of progression to about 25 percent, which is pretty good. It was therefore recommended that patients use the AREDS vitamin.
Things to remember about that are that it is not for everyone but for those who have signs of intermediate AMD. It is also not for people who are in their 30s who want to avoid getting AMD because their parents have it. We don’t know what those results would be. Beta carotene, what we all hear about when people say, “Eat your carrots to help see better,” which is vitamin A and other carotenes called lutein and zeaxanthin, naturally occur in the eye. They are natural antioxidants and sit in the retina and block out some light. The thought was that what if instead of using beta carotene, lutein and zeaxanthin could be used and even reduce the amount of zinc to see how that would work.
The other thing they tried to determine was whether fish oils helped in preventing the progression to advanced AMD. This was known as the AREDS 2 study. The answer to all of those questions from the AREDS 2 study were that fish oils really didn’t help one way or the other compared to the original AREDS formula; lutein and zeaxanthin were pretty good replacement for beta carotene; and there was a tiny risk of lung cancer in smokers with the beta carotene, so that was a good thing to replace anyway. So the bottom line is that there is an AREDS 2 formula, which has again vitamin C, vitamin E, this time lutein and zeaxanthin, and zinc. That is the formula that I recommend, that patients with intermediate AMD in one or both eyes or advanced AMD in one eye and not yet advanced AMD in the other eye follow the AREDS 2 formula to try to prevent progression of AMD.
MICHAEL BUCKLEY: That is great, thank you for elaborating on that. Related to that we have a question about buying supplements at the supermarket, where there are so many vitamins that are available, where according to this person they are all AREDS. Do you have any consumer tips?
DR. BRANTLEY: I have been down the aisle at the grocery store and pharmacy and there are a lot of eye vitamins, and it seems like every time I go there is a different one available. There are actually very few that follow the AREDS 2 formula. If it says AREDS 2 on it, then you are getting the right one. There are a couple of brands that we know are reasonably good. If you have any concerns, you can always look online by searching the ingredients or ask a pharmacist to help you find AREDS 2 eye vitamins.
MICHAEL BUCKLEY: We have time for a couple more questions about drug interaction and other medications. Kay from California is wondering if there is any evidence that ibuprofen could contribute or damage AMD and dosages for ibuprofen?
DR. BRANTLEY: Not that I know of, as long as one is sticking to the normal recommend doses of non-steroidal anti-inflammatory like ibuprofen. In general there are limits to what one should use, and I know that people are under the care of their doctor for low back pain or joint pain where they routinely take a non-steroidal like ibuprofen. I don’t know of any particular concerns for the eye above the normal concerns that someone would have in moderating doses of ibuprofen for general body health. So I would follow what your doctor prescribes.
MICHEAL BUCKLEY: I appreciate that. A similar question about medication for hypertension or thyroids, any factors that a person should be aware of that may affect their AMD?
DR. BRANTLEY: Not really. I think, again, in those cases it is important to treat hypertension. For instance, taking a look at the risk factors for AMD in big epidemiological studies—usually in heart disease studies—and looking at levels of macular degeneration, there are some of the same risk factors for heart disease, such as high blood pressure and high lipids, which may have slight effect on AMD. The way to look at it is in order to decrease my chances of having AMD maybe just a little bit, go ahead and make sure the other things are in order, like treating high blood pressure and high cholesterol. As long as you are using medication under a doctor’s supervision at a normal dose then I wouldn’t worry too much about it for the AMD.
MICHAEL BUCKLEY: Thank you. A final question on that—Diane from Texas is wondering, can AMD be a factor or indicator of other health problems?
DR. BRANTLEY: That is a tricky question. As you may guess from the name age-related macular degeneration, the number one risk factor is age. Age is a high risk factor for a lot of conditions. As we get older, we are more likely to have high blood pressure, high cholesterol, and diabetes. It would be very uncommon to identify that if one has AMD that leads to other systemic conditions; however, routine monitoring of the eye health is important, especially looking at the retina, because that sometimes can turn up other things like diabetes. In terms of the association of systemic conditions, there is probably a bit of association with heart disease. The same risk factors your cardiologist will discuss, exercise and eating right, don’t hurt at all for AMD as well.
MICHAEL BUCKLEY: Certainly good advice. Dr. Brantley, I would like to conclude with a big picture question. When you think about your lengthy experiences in the research lab and in the clinics seeing patients, do you have any advice you would give to patients and their families concerning any other common perceptions or misperceptions?
DR. BRANTLEY: Sure. In relation to this call, I would encourage patients or their family to feel free to ask questions, such as why are we given a drug or the frequency of taking the drug.
The other point to remember is what I mentioned earlier, that AMD does not respond exactly the same to treatment in every person. There are three different kinds of injections: Avastin, Lucentis, and Eylea, but they may not work equally well in every person.* Doctors will try really hard to provide the best individualized treatment. The best way to do so is seeing how well you respond to the injection. Therefore it is not surprising that some people may get more injections than others or receive more frequent injections. Feel free to ask your doctor these questions.
MICHAEL BUCKLEY: Dr. Brantley, once again thank you so much for being part of the Chat, you gave great advice that was very clear and concise and we hope our listeners found it helpful and empowering. This concludes today’s BrightFocus Chat. Thank you to all the listeners today who submitted some great questions and made this a very helpful discussion.
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) for the treatment of wet macular degeneration. Learn more about this treatment.