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Man: Medical news and research from the Ï㽶ÊÓƵ of Utah physicians and specialists you can use for a happier and healthier life. You're listening to The Scope.

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.

Man: We're your daily dose of science, conversation, medicine. This is The Scope, Ï㽶ÊÓƵ of Utah Health Sciences Radio.