Search for tag: "degeneration"

Interviewer: Age-related macular degeneration is a leading cause of vision loss in adults in the United States. The effects on the central vision caused by this disease can significantly impact your life, including the ability to do daily activities, the things you enjoy, and it could also lead to a loss of your independence. However, the good news is, if caught early, the progress of the disease can be slowed.

Dr. Monika Fleckenstein is a professor of ophthalmology and vision sciences at the Moran Eye Center. She's a retina specialist with an emphasis on this condition. Dr. Fleckenstein, let's start with what is age-related macular degeneration. What's going on?

Dr. Fleckenstein: Yeah. So age-related macular degeneration, and we usually say AMD, this is a disease in the back of your eye, and it causes that your central vision may get worse over time. As the name says, the most important risk factor is your age, where you cannot do a lot about it. But we also know other risk factors, which is, for example, smoking or unhealthy lifestyle. And we also know that there's a strong genetic component in this disease.

Interviewer: You called a . . . it impacts your central vision. Is that what you said? Explain what that means.

Dr. Fleckenstein: Yes. So if you look at a paper and try to read, you do this with your very central vision. So this is the area of sharpest vision. This is an area in your eye which we call the macula. And the very center of this macula is the fovea. This is actually the area of sharpest vision, and this is the area you need for reading, for recognizing faces. So this is the highest resolution in your eye.
How Age-related Macular Degeneration Impacts Daily Functioning

Interviewer: I want to know how age-related macular degeneration impacts people's vision in their daily functioning. Talk to me about that, from what you've seen with your patients.

Dr. Fleckenstein: We have different stages of age-related macular degeneration, early stages where you may not experience any symptoms, and then we have the later stages of the disease that you may develop a grayish area in your central vision. In certain subtypes of the disease, you may even develop a central dark area where you're not able anymore to recognize faces or read.

The symptoms patients experience is dependent on their disease stage, but usually, when I see patients with earlier stages, I actually ask them, "Do you have difficulties in dim light?" And so when you go to a restaurant and if you try to read the menu and the light is dimmed and maybe candlelight, this is actually where the patients realize first symptoms. Then also, when they come from bright light outside entering a room, and they may realize it takes them longer to adjust to these changing light conditions as before in their life or compared to the people they are surrounded by. So these are typically the first symptoms of the disease.

And so in later stages, when there is the real damage of the cell layers, the photoreceptors, patients may experience that they have difficulties to read. In very late stages, patients may even not be able anymore to recognize faces. And this is probably, you know, the end stage of the disease where they are not able anymore to read or recognize faces.
Early Detection of Age-related Macular Degeneration

Interviewer: And the importance of early detection in age-related macular degeneration, it's pretty critical, from what I understand. Can you expand on that?

Dr. Fleckenstein: Most sad situations are those where patients have the wet stage and did not receive treatment, and then you face a stage where treatment is not possible anymore or is not really effective anymore if patients have developed scar tissue. And this is why it's so important that if you realize symptoms, never hesitate to reach out to your doctor and ask to have a look.

And when I'm seeing actually my patients with earlier stages of the disease, I explain to them the symptoms of the later stages and tell them, "Please never hesitate to contact me and my team if you experience these changes." And I even tell them it's, you know, "Even if you do not have these specific changes, but if you have a weird gut feeling, please reach out," because sometimes, you know, patients just experience something is off, something is weird here. I cannot really say what it is. Never hesitate. Try to be seen by an ophthalmologist just to make sure that nothing is going on.

Interviewer: And if it's caught early, there are some things you can actually do about it. Tell me about that.

Dr. Fleckenstein: In the earlier stages of the disease, there are certain constellations or certain findings in the back of your eye where we would recommend that you take certain nutrition supplements. So it has been shown in a large clinical trial, the AREDS study, that a certain combination of supplements may delay the progression to late stages, but just if you have a certain constellation of the disease. So the study has also shown that just taking these supplements without having any sign of AMD will probably not have a positive effect. But if you have certain signs, it has been shown that the disease may be slowed down.

In general, we would always recommend, but this is more or less a general recommendation to the whole population, to have a healthy lifestyle, not to smoke. And actually Mediterranean diet has been shown, not only in age-related macular degeneration but also in cardiovascular diseases, that this can be beneficial to prevent the development of macular degeneration and also of the late stages. And Mediterranean diet, this means vegetables, fruits, olive oil, fish. So more a combination of nutrition into this direction.
When to Get Checked for Age-related Macular Degeneration

Interviewer: So since catching it early is so crucial, how often should somebody actually get their eyes checked for macular degeneration?

Dr. Fleckenstein: Yeah. So this really depends on age. So the American Society of Ophthalmology, they actually recommend to have an eye check when you become 40. Then it highly depends if your ophthalmologist finds anything, if you have any signs of a disease in the back of your eye. With ages of 65, we would recommend yearly eye exams. But of course, if you have a positive family history for age-related macular degeneration or if you have certain risk factors, I would recommend to be seen by an ophthalmologist more often and even in earlier ages.
Diagnosing Age-related Macular Degeneration

Interviewer: And in the diagnosis part, are you able to diagnose the disease? How far in advance before a person starts experiencing symptoms are you able to diagnose the disease with the equipment you have?

Dr. Fleckenstein: So we can see on a micron level changes in the back of the eye. Within the last decades, we have seen such a rapid improvement on resolution. And again, we can see tiniest changes in eyes. We indeed also see patients without any symptoms who are not aware of having any problems, and we may pick up earlier signs of the disease, and we can certainly see if macular degeneration is present or not.

Interviewer: That peace of mind is probably great for a lot of patients when you tell them, no, that's not it, that's something else.

Dr. Fleckenstein: Yes. But, you know, I tell my patients as well, as the time has changed so much and we have these dynamics right now, having the diagnosis of AMD today is something completely different than 20 years ago.

Interviewer: And why is that?

Dr. Fleckenstein: Because first of all, I believe within the next 10 years, you know, we will have more treatments available, and for the wet late stage where everyone is so scared about, we have wonderful treatment available, and this treatment really works well. And I always say I have respect for the wet late stage, but I'm not scared of it anymore because if this is treated well, patients can keep their vision for many, many years.

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Interviewer: So Leah, tell me your name and your title. What do you do here?

Dr. Leah Owen: My name is Leah Owen and I am a Chief Resident in ophthalmology here at the John Moran Eye Center.

Interviewer: So you've recently had some new research come out. What can you tell me? What is it about?

Dr. Leah Owen: Well, I've been fortunate enough to work with Meg DeAngelis, who has a lab here at the Moran Eye Center. Together we've studied some of the genetic causes for Age-related Macular Degeneration. This disease effects a lot of people age 60 to 65 and over, and is present in two different distinct forms. And one, people may have heard of as the dry form and the other is termed the wet form of Macular Degeneration. We studied specifically some genetic causes for the wet for of Macular Degeneration so that we could better understand what causes it on a genetic level and hopefully use that information to design more targeted therapies for treatment of this condition.

Interviewer: Where was it published?

Dr. Leah Owen: It was published in I.O.V.S.

Interviewer: What does that stand for?

Dr. Leah Owen: Investigational Ophthalmology and Visual Sciences. We have collaborators all over the world. We replicated our findings within patients from Korea, from Ireland, and from Greece. And so we have wonderful collaborators who are co-authors on our paper from those countries as well as collaborators at Harvard who we worked with on the initial patient population. And all of them are co-authors on the paper.

Interviewer: So what did you uncover here that was new and surprising to you?

Dr. Leah Owen: Well, we looked at a gene pathway that is involved in the specific problem in Wet Macular Degeneration which is that there are blood vessels that grow in your retina, which is the back part of the eye that's very responsible for your ability to see. And these blood vessels disrupt the normal architecture of your eye so that you're no longer able to see within the central portion of your vision. You can't recognize faces. You can't drive. That's the part of your vision you use most on a daily basis. So this condition affects your quality of life and it affects your vision quite drastically. In fact, it's responsible for greater than 70% of all legal blindness that's relate to Macular Degeneration. So it's a very significant problem and we need to find better treatments for it. We looked at a gene pathway that's known to form blood vessels since that's such a prominent part of this disease. We looked at certain genes in that pathway and within individuals who had Wet Macular Degeneration. We looked for any mutations that were present in those people who had Wet Macular Degeneration and compared that with genes of people who were matched, and otherwise identical, but who didn't have Wet Macular Degeneration so that we could find mutations that were specific to people with Wet Macular Degeneration.

Interviewer: So where could this lead? I know you mentioned new treatments. AMD is a big problem and is this a piece of the puzzle? Where do you see things headed next?

Dr. Leah Owen: Yeah, this is a really exciting piece of the puzzle. We've described several mutations that are present just within one of the genes we looked at in this larger pathway. And so it points us to this gene being important in the Wet Macular Degeneration disease process. And this is a gene that although we've known about it, we haven't targeted therapies directly towards the activity of this gene. And so I think our research raises the possibility that targeting this gene and this gene's function within Wet Macular Degeneration disease process might be a more effective way of treating it. And so going forward we are going to ask that very question.

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Interviewer: Dr. Paul Bernstein at the Moran Eye Center. Let's talk about some of the trials and some of the work and research that have been done into AMD and what you've discovered.

Dr. Paul Bernstein: Okay. We at the Moran Eye Center have been very involved in many of the key clinical studies for age-related macular degeneration. One of our primary treatments is a drug called Lucentis, which involves injections once a month of a medicine into the eye every month for age-related macular degeneration for the wet form.

Interviewer: And that's where the veins are starting to come into the eye?

Dr. Paul Bernstein: That's correct.

Interviewer: What does this medication do? Does it just stop that?

Dr. Paul Bernstein: The Lucentis and similar drugs, when injected into the eye, combat the growth of blood vessels. They actually interact with the signal to grow blood vessels, a compound called VEGF or vascular endothelial growth factor.

Interviewer: We learned in our previous podcast that what's going on there is that those cells are sending those signals to grow those blood vessels, and this tells it to stop.

Dr. Paul Bernstein: Yes.

Interviewer: Okay.

Dr. Paul Bernstein: It just blocks the signal right there.

Interviewer: Gotcha.

Dr. Paul Bernstein: It binds them, and the signal can no longer interact with the receptor to grow the blood vessels, and the blood vessels that are abnormal begin to get smaller and kind of wither away. After the drug wears off in a month or so, we have to give another injection into the eye.
So, we're trying to develop longer acting versions of the drug, and we're involved in some early stage clinical trial planning of either reservoirs that can be implanted into the eye that will slowly release a compound that would block vascular endothelial growth factor. We're also trying to look at different ways to get the medicine across the sclera, across the white part of the eye instead of using a needle, trying to use electrical impulses to get the drug to cross the eye.

Interviewer: Interesting.

Dr. Paul Bernstein: We would love to have a drug that could be just given as an eye drop. As you know, we have many medicines we give as eye drops. The challenge is that the retina is the back of the eye, and trying to get a drug to go all the way back and interact with the retina is difficult. Drug companies are very actively trying to improve that process.

Interviewer: So I suppose a pill, an orally taken thing, is just completely out of the question?

Dr. Paul Bernstein: People are looking at pills for macular degeneration that could combat the growth of blood vessels. The process is the macula and the eye is a very small part of the body.

Interviewer: Yeah.

Dr. Paul Bernstein: You have to worry about side effects and other reactions.

Interviewer: Sure.

Dr. Paul Bernstein: We certainly like the idea of local delivery, of targeted delivery to the eye.

Interviewer: Yeah. That's interesting. And what other kind of research of trials are you involved in or do you have going on?

Dr. Paul Bernstein: Well, we were one of the centers for the Age-Related Eye Disease Study, too, the AREDS 2 Study. We're really trying to understand the role of nutrition and nutritional supplements in age-related macular degeneration. This was a very large trial. There were nearly 100 centers across the country. Over 5,000 patients were in the study. It lasted five years. They had to come in every few months for eye examinations and to be given their supplements or placebos. It was definitely a placebo-controlled trial to really understand how these supplements work.

Interviewer: In a situation like that, I think you gave me a hint. How would you even know where to start and what to look for as far as nutrition that might be helpful? It sounds like you said these two things are high concentration in the eye, and that's where you started.

Dr. Paul Bernstein: Yes. So, the lutein and zeaxanthin are particularly interesting because the macula, which we all hear about for macular degeneration, is technically the macula lutea, which means "yellow spot" in Latin. And the macula uniquely in humans and fellow primates concentrates yellow compounds from our diet, the lutein and zeaxanthin. So I was always fascinated as to why nature went out of its way to put these two compounds that are antioxidants and light screening compounds directly into the back of the eye.

Interviewer: So somebody would take this supplement, and you would look to see if the concentration increased in their eye. Is that what you were looking for?

Dr. Paul Bernstein: That was in part. We were a sub-study in the trial to do measurements of the macular pigment levels, but ultimately for a national eye institute sponsored study, we're looking to see if it is effective with whether we can decrease the rate of progression to advanced age-related macular degeneration. That was the ultimate endpoint in the study. We have to see that we are getting an effect.

Interviewer: Yeah. Because if you increase those compounds, who cares if it's not solving the problem?

Dr. Paul Bernstein: That's exactly right.

Interviewer: Yeah. Interesting. What else do you have going on? You mentioned something on the horizon. Can you talk about that a little bit?

Dr. Paul Bernstein: We are looking at some other trials trying to interact with the immune system and the complement system. There is some exciting work as some of my colleagues here in the Genetics have discovered that the inflammatory system in the eye may be part of macular degeneration. So drug companies are developing new compounds that could interact with the complement system. Those are very early stage trials, and we're very hopeful that we can get involved in preventing macular degeneration earlier.
Other studies are to improve the compounds that we use to treat wet macular degeneration by doing combinations. Just like in cancer and chemotherapy, we know that there are multiple pathways that need to be attacked, and we are about to be a part of a new study that will be involved in even a second injection in the eye of a different compound. So it's a large commitment for patients to be in studies such as that.

Interviewer: So what's the theory there with the inflammatory system that's causing the problem? Is that, like, inflammation in other parts of my body, but it's happening in my eye? What would cause that?

Dr. Paul Bernstein: Inflammation as part of macular degeneration relates, we think, to the formation of drusen, the yellowish deposits we see underneath the retina. That is a very important sign of early macular degeneration. This causes damage to the cells and also contributes to the stimulus of new blood vessel growth underneath the retina.

Interviewer: So the thought that this is happening in the immune system that's trying to fight it is actually causing more harm than good. Is that what I'm hearing?

Dr. Paul Bernstein: We think that there may be a problem, and modifying that, that's what we need to test in these trials.

Interviewer: Any final thoughts for our listeners about the future of research trials?

Dr. Paul Bernstein: We always are looking to improve treatments. We've been very gratified by the improvements that have occurred in the last two decades for macular degeneration. We especially appreciate the commitment that the patients who join these trials have committed to this to trying to help both themselves and to others.

Interviewer: Could somebody listening be part of one of these trials? How would they make that happen?

Dr. Paul Bernstein: They need to talk with their doctor.

Interviewer: Okay.

Dr. Paul Bernstein: If you have macular degeneration, the best thing is to ask your doctor. Ask what trials are available, and how they could be improved on the standard therapy that we have now.

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Interviewer: Are women more likely to get macular degeneration than men? We'll examine that next on The Scope.

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Interviewer: Dr. Margaret DeAngelis is at the Moran Eye Institute. She also is on the Utah Women's Eye Health Board. Let's talk about women and macular degeneration. Maybe I'm wrong on this. I kind of thought generally it was men that got it, but that's not the case.

Dr. Margaret DeAngelis: No. Women, it's actually been shown, in two studies done ten years apart from each other in what's called a meta analysis where you combine all the studies that are out there, that women are at higher risk of getting age-related macular degeneration than men. Now, why is that you might ask.

Interviewer: Why is that?

Dr. Margaret DeAngelis: Why is that? Well, we're not sure. So some people, some groups have looked at that it may be due to hormone replacement therapy or estrogen that increases one's risk so certain groups are studying that. Some groups have found an association while other groups have not so there's a lack of consistency from study to study. So we still don't have the answer for why women are at risk. Some people have argued that maybe women are more inclined to join studies, to sign up for studies, but that hasn't been the answer either. Or maybe women smoke more cigarettes or these other things, but after you've controlled for all these external factors, there hasn't been the answer there so we're still looking for the reason for why women are at a slightly higher risk. And we do know that genetics plays a strong role but that is equally so in men and women so what that means is if you have a first degree relative, either a parent or a sibling, a brother or sister, with age-related macular degeneration, you're at six to twelve times higher risk than somebody from the general population of getting age-related macular degeneration yourself. So it's highly recommended if you have a family member with age-related macular degeneration you should get your eyes checked age 50 and over at least once a year.

Interviewer: Six to twelve times more. Put that in perspective for me in relation to other things like smoking which has also been shown to cause macular degeneration or a relationship. How much does that increase my risk?

Dr. Margaret DeAngelis: It depends. Different groups including our group have shown that that's based on the number of pack year so if you smoked a pack of cigarettes a day for one year, the more cigarettes you've smoked or pack years your risk increases exponentially, and smoking by everybody has been shown to increase risk.

Interviewer: Got you.

Dr. Margaret DeAngelis: Please understand that that increases your risk, you're susceptibility. It doesn't mean that you will get the disease because you have a first degree relative or you smoked cigarettes. It means your susceptibility has increased. That's a difference between susceptibility and causality.

Interviewer: Is the direct relative susceptibility? Are we talking susceptibility if I have a first...?

Dr. Margaret DeAngelis: We're talking it increases your susceptibility, correct.

Interviewer: How significant is six to twelve times more susceptible? Put that in a perspective for me. Is it like, "Oh wow, that's a lot. That's frightening. Like you should go see the eye doctor right now."

Dr. Margaret DeAngelis: Six to twelve is a lot. If you're 50 years old and older, the American Academy of Ophthamology recommends that.

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