S2:Ep6 – Understanding Migraine & Light Sensitivity

TRANSCRIPT

Voice-over: Welcome to Spotlight on Migraine, hosted by the Association of Migraine Disorders. Join us for fresh perspectives by medical experts and advocates as we explore the spectrum of migraine and dig deeper into this complex disease. This episode is brought to you in part by our generous sponsors Amgen and Novartis.

Could phototherapy be an easy tool to add to your migraine management regimen? Dr. Rami Burstein explains how light impacts migraine as well as his research that shows promising results about narrow-band green light therapy. Stay tuned to learn about this risk-free option.

Since 2015, Amgen and Novartis have been working together to develop pioneering therapies in Alzheimer’s disease and migraine. Together, Amgen and Novartis share in a mission to fight migraine and the stereotypes and misconceptions surrounding this debilitating disease.

Molly O’Brien: Hello and welcome to Spotlight on Migraine. I’m your host, Molly O’Brien. Today we’re taking a closer look at light sensitivity and how different types of light can impact migraine. I’d like to welcome our guests, Dr. Rami Burstein — he’s a professor at Harvard Medical School — and Ajay Kori — he’s with Allay Lamp. Thank you so much for joining us.

Ajay Kori: Thanks for having us, Molly.

Dr. Rami Burstein: Thanks for having us.

Molly: And as a disclaimer, AMD does not endorse any specific products. This podcast is for informational purposes only.

I’m really excited to have you both here today. We’re going to talk about the vast amount of research, Dr. Burstein, that you’ve done over the course of your career, and you’re pretty well known within the migraine community. Can you talk a little bit about some of the research you’ve done that revolves around light and how it can impact migraineurs?

Dr. Burstein: Yes. So light exacerbates the headache for about 80% of all migraine patients. Light itself or this what we call “photophobia,” this extreme sensitivity to light, is not as debilitating as the pain itself. Patients want to get rid of the pain. It is one of the topmost bothersome symptoms that truly debilitates migraine patients. 

It is often not the pain itself but the sensitivity to light that makes them quit the work and go to a dark room, not being able to function at all, not being able to function anywhere they are, and really resort to social isolation. Well, when you do it by no choice, it is very stressful and uncomfortable, and you feel like you’re missing out on life while life goes by and you have to be in a dark room by yourself. 

So working with migraine patients for many years, we all learn to ask questions related to our ability to diagnose migraine and to ask, “Does it hurt on one side? Does it throb? Does it come with nausea and vomiting, sensitivity to light, sensitivity to noise?” We learn to ask it without really stop for a second and figure out what is it all about.

Well, migraine is a general brain disease. There are multiple symptoms, and sensitivity to light is one of them. Because it is one of the top reasons for why migraine patients are debilitated by migraines, about ten years ago, I slowed down and started to ask the question, “What is it about photophobia? Can we figure out how is it that light makes a headache more painful?” And if we can figure that out, maybe one day we can figure out a way to target only photophobia, the sensitivity to light.

So in 2010, when I got into this topic to begin with, I did kind of a tour among migraine patients who are blind and found that migraine patients who are blind and can see no light because the optic nerve is cut are not photophobic during migraine. But migraine patients who are blind but can see light — it’s called light without sight, like if you close your eyes and you’re in a dark room or a light room, you can see the light, but you can’t see anything. These migraine patients do suffer from photophobia. Light makes their headache more painful. 

And along this study, what we discovered was that it is really on cloudy days, snowy days that the light bothers them more often. And on these cloudy days, just the physics suggest to us that the light tend to be more on the blue family of light. 

It took us a while to understand why blue light makes the headache more painful in blind migraine patients, which led us to the first discovery of a pathway that originates in the eye and goes to a part of the brain that’s called the thalamus, where pain signals that are activated during migraine converge on visual signals on visual pathways that come from the retina and go to the visual cortex. And it is along this crosstalk between the pain pathways of migraine and the visual pathways that come from the eye that the light can modulate or can facilitate activity of neurons that are sensitive during migraine and make the headache more painful.

The attractive part about this study was that it was done on blind migraine patients. Nobody studied them before. What we learned was a lot, but the most important part of this study was the fact that it brought to our attention the possibility that color plays a role in migraine-type photophobia. 

So we launched a large study in 2012 where we tried to figure out whether different colors of light have different effects on migraine-type photophobia. We exposed migraine patients to different colors of light, and the bottom line was the follow. We found that blue and red light make the headache most painful. Amber and regular room light make the headache painful, but not as painful as blue and red. And to our surprise, green light actually made the headache less painful. Not only it made the headache less painful, but it also decreased throbbing and shrunk the area of the headache. If it was in the front and the back, it only moved to the back or only to the front. It slowly began to shrink.

When we moved along to try to explain this finding, we found that green light generated smaller electrical signals in the retina in the human eye, which means that the electrical signals that the eye sends to the brain is smaller in response to green light than in response to any other color of light. Not only that, but when we recorded the electrical signal in the cortex in these patients, we found that the electrical signals that are generated in response to green light were significantly smaller than all other colors of light. It all matched what patients told us in their perception.

When we published this data, the findings got a lot of attention, with belief, mostly in the media, that there’d be a very fast and quick and cheap answer to migraine-type photophobia by taking regular green light, or color them with green, putting in them green color, and give it to patients. When I said to the BBC, which was the first one to jump on that, that that is not the case, they virtually wanted to turn off the microphone and move on, because at that point, it was not that attractive, that they could tell patients, “Go out and get green lights and use it.”

Molly: Can you tell us a little bit more about the green light and the work that you’ve done with that — again, multiple studies that you’ve worked on, multiple research efforts that you’ve done in that behalf, as we focus on that green light and how it can affect patients — as well as, can you tell us if a certain brightness of lights matters?

Dr. Burstein: The main goal was to allow migraine patients to continue to function in an environment where they can see enough to read, write, socialize, continue to work — if they’re a psychiatrist, treat a patient; if they’re a physical therapist, treat a patient — whatever to continue to do what they do without going so the experience of having any source of light making their headache more painful. 

The green light that we use, which is a narrow band of green light, it escapes the ability of photoreceptors in the human retina that respond to blue and red to be activated. So it only leaves the green receptors active. It appears to create this environment where you can see. Basically, your cortex believes it’s the dark, but you can see. 

And so that was the solution to photophobia. The green light gives them a solution. Patients who come to the room within five minutes would say that they would rather been in the green room than in a dark room, that the green light does not bother them, and that they don’t feel isolated. This was the main goal of everything that we started. 

What we did not anticipate is that the headache will get better, will decrease in intensity, which it does in a large number of cases. And maybe the other two more surprising findings that we had was that almost unanimously, they describe green light as calming, soothing, relaxing. And after enough time in green light, they talk about the fact that their anxiety gave way to feeling calm and their irritability gave way to feeling relaxed.

And so this is a whole transition from negative effect to positive effect. In addition, they begin to talk about cognitive clearance, where they speak faster. So migraine patients, most of them have a hard time to come up with the right words. They want to say, “Today is Tuesday,” and they cannot come up with the word “Tuesday,” or they come up with the word “Tuesday” and it doesn’t come out right. After several hours in the green light, they talk faster. They say that they’ve a much easier time to find the right words and to say it correctly. 

So what it teaches us is that the green light really is a non-invasive phototherapy. It calms down cortical activity, mostly the cortex. These are the findings that we did not predict, we did not expect. We didn’t think that this is where green light will go. 

Where did it start that green light is associated with more relaxing and calming effect? We really don’t know whether it comes from the past, from evolution, from whatever. But the surprising part is when I start talking to other experts like ophthalmologists and I say to them, “Guess what I found.” 

Before I tell them, they’re already telling me, “You found that green light is calming.” 

I say, “How do you know?” 

They say, “Because when we do eye exams in our patients who are sensitive to light because of eye diseases, we only use the green lamp, because everything else I more painful to them. They can’t handle it.”

So among people who really spend their lives with color, it is almost a common knowledge that the green light is associated with soothing, calming, relaxing. It’s just that nobody put it together until we came up with this observation and then took it into the science of, Why is it that it is this particular narrow band of green light? What happens if we move it a little bit to the right and a little bit to the left of the human visible spectrum? Why does it get worse so quickly? The science behind it is fascinating, and it all makes sense. The beautiful part about it is that everything makes sense.

Molly: Yeah, it really does seem like you took all of the pieces — the common-sense pieces — molded them together, put them into the perfect puzzle, and now here we are. You have the research to back you up, and now we can move forward.

So do you feel like your research has translated well into therapeutic work?

Dr. Burstein: The first lightbulb that I used cost $50,000, and it is because it is a light that is approved by the FDA for diagnosis of different retinal diseases. When things need an approval of the FDA, by definition, you need to spend many, many millions of dollars to go through the testing, and it becomes more expensive. It is how research works, and it’s one of the reasons why the gap between a discovery in research and the way to go into patients takes generations — many, many years, not three years. 

Basically, if you put it together, we discovered the effect of the green light in 2016, and four years later, we are in the market with a lightbulb that costs just about $200 or a little bit less.

Molly: I would love to hear, because there is so much research behind it, Dr. Burstein, that you have put into this — many, many years of research — would love to hear how, Ajay, you took that and kind of translated it into a product that people can use — but also just the idea on how you move forward with something as simple as a green lightbulb, but making it available for people to use, that doesn’t cost $50,000.

Ajay: Great question, Molly. So I’m actually the son of another migraine researcher, so I’ve actually been around migraineurs my entire life and seen how debilitating the condition is and was fortunate enough to meet Dr. Burstein on several occasions. And one of those times recently, he pulled me aside and showed me his research on the impact that a narrow band of light can have on migraineurs, and it just blew me away. 

And the particular challenge we had was, as Rami mentioned, the device that he used in his original studies was $50,000, and it’s because just a normal green lightbulb, which you can buy off the shelf, doesn’t work. What you need is a device that only projects about 10 nanometers of light. And the importance of that is because when you have a wider range of light, which you have in a green lightbulb or if you turn you Philips Hue to a green setting, you’re essentially also hitting the blue and yellow receptors in your eye, which Rami talks about being extremely aggravating to someone having a migraine.

So you have to have such a narrow band of light that you’re only activating green and not activating blue or yellow at all. And those type of devices are very precise, and very few of them exist in the world — one of them up at the lab at Harvard, which was used for the studies.

I have been lucky to start a couple companies in the past, and through those connections, we were able to actually find our way to the largest LED manufacturer in the country, who happens to also be someone who truly cares about improving well-being of people. He designed all the lights in the Space Station, and he has, I think, about 200 patents to his name, most of them dealing with helping improve human health.

So it just was very fortuitous that he also was very interested in helping bring something to market that could potentially help millions of people, especially people who have migraines who have suffered enough. And he was able to essentially engineer an LED that only displays that 10 nanometers of light and produce a device in a consumer-friendly application that leverages those LEDs. 

So what we ended up building is the Allay Lamp. And this device, even though it’s portable and people love being able to take it around from place to place, actually has 34 separate of these very, very specific LEDs in it.

Molly: That’s awesome. If you turn it sideways, we can actually see the green in it. That is incredible, and what a backstory too. It sounds like working connections — again, the pieces kind of came together to make this all happen in just the right organic kind of way, which is really exciting.

Can we talk a little bit about the practical use of green light? Obviously, all migraine patients are different. We all have and experience our attacks differently. So when we’re using green light, if it interests migraine patients, are there any standards or recommendations, dosages?

Dr. Burstein: Thank you for asking. Everything that we learn is that other lights will neutralize the effect of the green light. You really want to use it in a room where it is the only source of light. So we did not develop it to allow you to use computers, televisions, iPhones. It will take us another generation or two to get there. We developed it to allow you not to be in the total darkness where you cannot function. We’re aware of the fact that there is an issue with the fact that the green light — that you will not have the same benefit if you’re using it with your computer or watch television. Because of the blue light or the red light, that will neutralize it right away.

There is no medicine in human history — it doesn’t matter how expensive it costs — that helps 100% of the patients. It just doesn’t happen. Clearly, the Allay Lamp and the green light are not going to help every migraine patient. Will it help the majority of them? Yes, it will. Will it help all of them? No, it will not help all of them. 

Why should they try it? Because it doesn’t put any chemicals in your body. Because everything that we do in medicine is based on the simple equation of risk-benefit ratio. If the benefit outweighs the risk, we do it. If the risk outweighs the benefit, we don’t do it. We think the Allay Lamp has zero risk and only potential for benefit.

So there are several ways to use it. I think that the most practical way is not to look at it directly, to turn it to a maximum brightness, and to put it on a high shelf behind you. Or if you can mount it to the ceiling, it’s even better, because when you mount it to the ceiling, it brights up the entire room to give you enough light to see anything, to read books, to see people, to talk to them, to put your kids to sleep, to cook, to clean, to bathe, or to do anything to continue to work. 

And the experience that we have now — which is not the end of the story, but this is as long as we studied it — letting patients spend two hours with it gives them the best chance of getting good benefit. If they spend way less time — 30 minutes or 60 minutes — they will begin to see benefits, but they will not reach the maximum that we see. We don’t know if spending more than two hours is even more beneficial, because we didn’t study it, but we know now that not looking at it directly and spending at least two hours in it is critical.

Molly: Do you find that the green light can help patients in acute treatment or preventative treatment, and again, are there any recommendations in terms of when to use green light?

Dr. Burstein: It helps migraine in the acute phase of a migraine attack. The effect can outlast the exposure to the green light for certain amount of time, which we don’t have enough data to put together for a large group of patients. Regarding prophylactic, whether it can prevent a migraine attack, that is something that patients will tell us as they use it and we will get their testimonies. It’s where our knowledge [is] at. We haven’t done the studies, and we don’t have the answer. We don’t have the data to answer the question.

Molly: You mentioned before, Dr. Burstein, that there aren’t really any risks associated with using green-light therapy. I’m wondering, a lot of migraine medications and treatments, they’re not safe to use on pregnant women and not necessarily safe for children either. I don’t know if you’ve included this in any of your research, but I’m wondering if green-light therapy could be appropriate for pregnant women.

Dr. Burstein: Sure. There’s no risk at looking at green light when you’re pregnant. Yes, children — as you know, there are very few studies that got FDA approval for medication for migraine that are approved for adults, for many reasons. A lot of them are financial. So using green light, which does not need an FDA approval, makes a lot of sense.

Molly: It’s exciting to continue to hear about new research happening and, of course, new products. We’ve seen a lot of new therapeutics being developed just over the past two years, so it is really exciting to see new products come to market, because as you said, it’s a long process to get them there.

So, Dr. Burstein, before we let you go, I can’t let you leave here without asking — a couple years ago, you were one to throw out the first pitch at a Red Sox game thanks to some of the work you had done for migraine research. I want to ask you what that experience was like and just to be there at Fenway Park throwing out the first pitch.

Dr. Burstein: The reason why I got to throw the first pitch is because a few emails and the social media had spread the word that my mission was to raise enough money to educate non-headache doctors about headache, and that means OB-GYN, psychologists, psychiatrists, ophthalmologists, dermatologists, neurologists, anesthesiologists, a whole group of ah, internists, internal medicine, family doctor — all those who really see this large, large, large patient who often don’t get an access to a tertiary headache center. And we thought that the right thing to do is to reach out to them to teach them about the diagnosis and treatment of migraine.

So I started this fundraising, and I think that I raised almost as much as the American Heart Association. And because I was the individual that raised the largest amount of money, they let me throw the first pitch. It was really fun, very fun. I threw a 40-some-miles-an-hour strike. It was fun.

Molly: That’s amazing! Not only did you throw a fastball in there, you said it was a strike too. And as baseball season approaches, I couldn’t let you leave without sharing that experience for us and, most importantly, the large amount of money you’ve raised to continue educating non-headache doctors just how important it is to help their patients and to really educate them about migraine, which is so important. And I think we really know that here, if you’re listening at home. A big thanks goes out to you.

And that wraps up our episode of Spotlight on Migraine. I’d like to thank our guests, Dr. Rami Burstein and Ajay Kori, with Allay Lamp. If you want more information on migraine, you can head over to migrainedisorders.org. Until next time, I’m Molly O’Brien.

[music]

Voice-over: Thank you for tuning in to Spotlight on Migraine. For more information on migraine disease, please visit MigraineDisorders.org.

This podcast is sponsored in part by Amgen/Novartis.

*The contents of this podcast are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The speaker does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.