How Does Space Travel Affect the Eyes?

How the human body reacts to the transition to deep-space travel – and 
then adapts, or doesn’t, to lengthy periods in a microgravity environment – 
remains a largely understudied area. Our guest, Prem Subramanian, MD, 
PhD, chief of neuro-ophthalmology at the University of Colorado School of 
Medicine, talks about how space travel, including long-duration spaceflight, 
affects the eyes and how advancements in neuro-ophthalmology are helping 
astronauts. He also discusses treatments for thyroid eye disease and 
strabismus and shares research that seeks to understand eye issues in 
patients who’ve suffered from multiple traumatic brain injuries.

Transcript

Chris Casey:

Welcome to Health Science Radio where we talk with researchers at the University of Colorado Anschutz Medical Campus about the ways they are innovating and advancing healthcare. Today we'll be talking about space travel and what it does to the eyes. It's not something you'd normally think about, but for over a decade, NASA has been doing MRI scans on astronauts after their missions. We will also discuss thyroid eye disease and research that seeks to understand eye issues after multiple traumatic brain injuries. My name is Chris Casey and I'm the director of digital storytelling at the CU Anschutz Office of Communications. I'm joined in studio by Dr. Thomas Flaig, our vice chancellor for research, and we're recording as always in the historic Fitzsimons Building.

Our guest is Dr. Prem Subramanian, Neuro-ophthalmologist, who received his MD and PhD in Molecular and Human and Genetics at Baylor College of Medicine. Prem is the Clifford R. and Janice N. Merrill Endowed Chair in Ophthalmology at the Sue Anschutz-Rodgers Eye Center and is also professor of ophthalmology, neurology, and neurosurgery, as well as Vice Chair for Academic Affairs at the CU School of Medicine. He is also an adjunct professor of surgery at the Uniformed Services University in Maryland. Prem is a founding medical staff member of the Marcus Institute for Brain Health, which serves to improve the functioning of patients with traumatic brain injury or TBIs. His current research is focused on finding more effective treatments for patients at risk for progressive thyroid ophthalmopathy, developing better treatments for patients with increased intracranial pressure, and using vestibular and visual therapies to overcome visual and balance dysfunction after TBIs. Now, there were a lot of polysyllabics there that I made it through.

Thomas Flaig 

I'm glad it's you, not me.

Chris Casey 

Well, Tom, would you like to ask Prem, would you like to get the interview rolling?

Thomas Flaig 

I'd love to jump into this interview and what a great topic, really exciting area and some great research and work being done here at CU Anschutz. So, you recently collaborated with SpaceX Polaris Dawn astronauts and colleagues at CU Boulder to study how eyes change in space. So can you tell us more about your research there and how'd you become involved in that project?

Prem Subramanian 

So as Chris mentioned, for more than a decade now, it's been recognized that astronauts get changes in their eyes. And actually when we first went into space, when people first went up, they realized that they would get something called hyperopic shift. They would get a little farsighted, and that's because of some swelling in the back of the eye, extra blood flow that happens when you go into microgravity. And then when people started spending months in space on the International Space Station, it was recognized that there were other changes happening, including swelling of the optic nerve, even some hemorrhages in the retina, and concern came up that this could actually lead to problems with vision. So no one knew why this was happening. There's a terrestrial disease called pseudotumor cerebrei, or idiopathic intracranial hypertension, that also causes people to have swollen optic nerves. And so it was thought maybe there was something with that, that the pressure was going up inside their head.

We realize that wasn't the whole answer. And so now, because we don't understand what is actually happening, we call it spaceflight associated neuro-ocular syndrome, and it's just a description of these changes that happen. But some of it almost certainly happens because blood flows up to your head and stays there when you don't have gravity to pull it back down towards your feet like we're designed to do.

And so the work that has been done over the years has been to look at changes as they occur over time up on the space station, but the work specifically with SpaceX and Polaris Dawn was to see what changes occur in real time as a person transitions from a terrestrial environment to a microgravity environment. And so the experiments that we designed along with my colleague Ali Anderson, who is an aerospace engineer at CU Boulder, our teams came up with methodology to measure changes in eye pressure and changes in axial length, length of the eye, because both of those things potentially are influenced by changes in blood flow to the choroid, which is a very vascular layer that sits right behind your retina inside the eye wall.

And so it's somewhat expansile and the volume of that can change pretty dynamically as someone goes from one environment to another. So that's really the basis of what we are trying to look at with the Polaris Dawn astronauts, what happens with their eye pressure. And so we used a sensor that can measure in real time, and then we also used a device that very accurately measures the length of the eye.

Thomas Flaig 

What a fascinating area. As you talk about there's a difference, there's probably these shorter-term trips, there's those that are in long-term orbit on the space, and then there's the deep space sort of travel. And it sounds like there's some short-term changes, you said, I think farsightedness and then possibly these longer-term. So in the actual operation of the flights, does that have any acute short-term impact? So if you're farsighted as an astronaut, does that impact things on the actual astronaut work that's being done?

Prem Subramanian 

Because of that, NASA actually developed, and some of you may have seen there were ads for these done by Penn and Teller years ago, spaceflight adaptation glasses, and then they were sold as something called Superfocus glasses. And these are glasses that have a viscous fluid in a compartment behind the lens that you can actually use a little slider that changes the shape of the lens in real time so that you can add a little bit of power to the glasses and use them up there in space. And then as you adapt or as things change, you can use the slider to help you to focus. So that was a device that was created to deal with that short-term problem.

Thomas Flaig 

I don't remember that, it's quite interesting. So it's dynamic enough that you wanted the ability to adjust it as you're, because I think if you're an astronaut, you're looking at this control panel, it's pretty important that you have good acuity of vision.

Prem Subramanian 

Absolutely. And one of the reasons I think it was found is because originally, now the Astronaut Corps is more diverse, but initially it was a bunch of men in their mid-forties who were pilots and they typically had excellent distance vision, but in our mid-forties, all of us start to need reading glasses. And so it accelerated that process and they went up there and exactly like you said, they looked at their control panels and said, "Oh geez, I can't focus on this thing anymore."

Thomas Flaig 

Interesting. Yeah. And so perhaps the issues then are different if people are going on a deep mission. If there's a mission to Mars or something like that, are the potential issues in health concern different for that longer-term deep space exposure?

Prem Subramanian 

That's the big issue because no one ever saw these SANS-type changes, the spaceflight associated neuro-ocular syndrome changes, until a person had been in space cumulatively for at least three months. And the really concerning thing about it is that we've had people stay now six months, nine months, 12 months, even a little bit longer and there doesn't seem to be a stopping point for when these changes plateau.

And while so far it hasn't been observed that anyone has developed any permanent vision loss or even visual impairment that required us to say, "Uh oh, you have to come back to Earth from this mission," the concern is obviously that if you put people in a spaceship and send them off to Mars where there's no real coming back until it's time and you're there at least 18 months in a microgravity environment, we don't want people to show up at the other end unable to see, unable to perform their mission and in a bad place. And so as a result, NASA has ranked SANS as the number two human health hazard in spaceflight with the only thing exceeding it being radiation exposure. Because when you go into deep space and you don't have atmosphere around you, all sorts of cosmic rays and things that never make it into our world are there for you to be exposed to.

Thomas Flaig 

So I'll ask this question. If it's a bad question, you could just disregard it, but so is the gravity situation, the effect of the eyes different if you're in deep spaceflight versus you're on a lunar, let's say you're on a moon base long-term in the future where you've got, I suppose some gravity there. Are there differences between those environments?

Prem Subramanian 

There should be, and of course we don't know because we can't simulate that reduced gravity as well here on Earth. There are some models that put people in a six-degree head down tilt. And so there's a laboratory in Europe that has been established where you can even modify the atmosphere because there's more CO2 in a spaceship or in the space station than there is on earth. And CO2 also can raise your intracranial pressure. So you can control some of these things and try to recreate a pseudo microgravity environment. But the theory is that if you have some gravity it should be protective and that – I'm talking about Mars – once you get to Mars and you're exposed to some gravity there, some of these changes would not be occurring.

Chris Casey 

So when you say, Prem, that NASA considers SANS potentially the number two health risk of astronauts traveling deep in space toward Mars, is there any projecting what they could be experiencing, what the risk is? Is it perhaps blindness? Is it perhaps their brain, just massive pressure within their intracranial area? Is there any speculation as to how that manifests?

Prem Subramanian 

Our concern is, just like in people on Earth who are exposed to pressure on their optic nerves for a long period of time, that there could be loss of the optic nerve, death of nerve cells, and that could lead to visual impairment. And so people could lose peripheral vision, they could even lose some of their central vision, their ability to discriminate details. And that is certainly the concern. There fortunately have not been neurological symptoms that have been reported by the astronauts. We do know that the brain does shift a little bit because of the fluid changes within the compartment inside your skull, but at least as far as we can tell, that has not led to any functional impairment.

Chris Casey 

And could you talk about these smart contact lenses that you worked on, collaborated on? What's the purpose of those and what function will they serve?

Prem Subramanian 

These were actually developed by an adjunct faculty member in our department, Kaweh Mansouri, who is in Geneva. And his goal was to develop a device that would allow for real-time measurement of pressure inside the eye. So it has a little strain gauge built into the contact lens, and then a wireless receiver that the person wears, and then it transmits these strain gauge data in real-time and collects them. And then you can't convert it directly to eye pressure, but you can see changes in eye pressure over time. So we repurposed that device, which he had developed as a medical device, to study these real-time changes as the astronauts are exposed to the acceleration of going to escape gravity, and then what happens once they actually get into that microgravity environment. We were particularly interested because the Polaris Dawn mission is the highest mission above Earth to have flown since the lunar missions actually. And so they went up above 300 miles above the earth, whereas a typical orbit is more like 170 miles.

Chris Casey 

And also another device I've seen writings about that you've been involved with is called QuickSee. Could you explain a bit more about that?

Prem Subramanian 

And that is a commercial device that was developed for measuring refractive error in the eye and does so by really accurately measuring the length of the eyeball. And it has some advantages in terms of the technology that it employs to make it pretty reproducible and also to make it easy for non-medical experts to use. And so the purpose of using it was because, I think I mentioned that the choroid, that blood-filled space in the back of the eye, we think it expands in spaceflight, and so that shortens the effective length of the eyeball and the QuickSee can measure that really nicely. So we were looking at those changes, again, how quickly they happened. Do they happen within six hours? Does it take several days? And how quickly might it change once someone comes back to earth?

Chris Casey 

What would be the next steps then with this Polaris Dawn research?

Prem Subramanian 

Some of the work I've done with Allie Hayman has centered around mitigation of some of these. So let's say it looked like there was a window of opportunity to intervene and maybe prevent some of these things from happening. We've published some work on using a short-radius centrifuge to create an artificial gravity, so it's not cool stuff like ‘Star Trek’ where the whole thing spins, but you would spend some time on a short radius centrifuge that would help to push some fluid back towards your legs and potentially reduce some of that pressure within the eye. There are techniques that have been done – thigh cuffs and things. The Russians have used these for years to try to trap blood down in the lower extremities so that you don't get as much pooling in the head. But those things are tricky to use sometimes, and we don't know how long someone can be safely exposed to it, how long you'd need to do it, but really a lot of it centers around coming up with ways to mitigate the effects and to prevent those changes from happening in the first place.

Thomas Flaig 

So maybe we should move to the next topic, but what a neat topic, and there's so many different elements to think about, the health of astronauts eyes so critical of their work, be that if they're going to deep-space missions or maybe they're going to be on a base on the planet somewhere that's got a low, but not zero, gravity and how we think about them. I think one, just to reiterate one point, these tend to be temporary changes. So when the astronauts return to the terrestrial setting, these are usually resolved?

Prem Subramanian

Usually, although we did publish a case of an astronaut who had persistence of that swelling of those SANS changes for 20 months after returning from the long duration space flight. And so you're right, most of the time it goes away and we still don't understand exactly why in that astronaut these changes persisted. And again, no visual consequence from it, but it is a bit concerning.

Thomas Flaig 

Well, again, maybe shifting gears, we could talk a bit about thyroid eye diseases, so something else that fits in your expertise. And there's some particular associations with that, including optic neuropathy and double vision. So how does your expertise fit in this idea of thyroid eye diseases?

Prem Subramanian 

About 50% at least, of people who get Graves disease, an autoimmune disease that causes hyperthyroidism, will get thyroid eye disease. And classically, this causes the prominence of the eyes and eyelid retraction and redness and sort of a stare.

But from a neuro-ophthalmologist's perspective, the things that really, I think, visually disable the patient are when they develop double vision because the extraocular muscles, muscles that move the eye, become tight. And also because those muscles when they swell, they can put pressure on the optic nerve as it exits through the back of the eye socket, which is a very narrow space. And so we have been doing work to try to better understand what leads to those changes in the orbital tissues and also how we can better treat or prevent those problems from happening in the first place.

Thomas Flaig

You think about some of the pathology of Graves disease and so forth, I've always thought of it just generally as there's a physical, disunion of this. And I guess that still fits with what you're saying, right? Where you're trying to realign to the musculature to remedy the double vision.

Prem Subramanian 

Yeah, that's exactly what we're trying to do. And there's been a lot of advances in the understanding of the molecular pathogenesis of thyroid eye disease, some of the cellular processes, involvement of various autoantibodies, and in particular the coupling of thyroid hormone receptor and insulin-like growth factor-one receptor, and how they drive the pathologic process. And so it is, some of it's at the very clinical surgical level, and some of it is centered around new drugs that have been developed to try to alter the trajectory of the thyroid eye disease and prevent some of these changes from happening in the first place.

Chris Casey

Fascinating. So there's always a lot of interest around traumatic brain injuries, or TBIs, which have multiple consequences for the victim of those. Movement associated with that, balance issues. Could you describe, Prem, some of your research associated with TBIs and just what's the goal of better understanding multiple TBIs?

Prem Subramanian 

My interest in this started from my time on active duty as an Army neuro-ophthalmologist. I was actually on active duty at Walter Reed Army Medical Center on September 11, 2001. And since that time had the honor of taking care of injured soldiers and others who came back from the wars and saw that they were experiencing a number of visual issues that were sometimes hard to characterize. We're really good at identifying when people have problems seeing out of one or both eyes where there's injury to the retina or the optic nerve, or even the brain, that results in visual acuity or diminished visual field. A lot of these service members were having trouble reading or they were having trouble, just saying, "Doc, I can't use my eyes together." And if you did traditional measures of eye misalignment, like you mentioned before, you didn't pick up much. And some people thought, "Oh, they're making it up because they're injured and they don't want to go back." But I thought that wasn't really the case and I and others started looking into this a little bit more.

And that has translated into the work that we're doing here and Jeff Hebert at the Marcus Institute and others, we're looking at the idea that multiple TBI, and again, these are mild TBIs generally, so it's not that someone loses consciousness for an extended period of time, but these people then develop problems with their balance system. And the balance system is really important for coordinating your eye movements as well. So the cerebellum, the part of the brain that controls balance, is also very important for integrating eye movements with body movement and for directing eye movements.

And so our research now has been looking at a couple of different things – looking at what eye movement abnormalities occur in people who have these vestibular problems after multiple TBI, and is there a correlation in the particular kinds of eye movement abnormalities that they have? So for example, are they unable to make a movement to another target? Are they unable to suppress making a movement to another target when they don't want to or do they overcompensate? That's one of the things we've found is that they become hypervigilant because they want to function and then they are very sensitive to motion stimuli or very sensitive to visual stimuli, like bright lights. They'll tell you, "I can't go into a Costco because it just destroys my ability to cope."

So that's where our research has been focused in. We're using methods of tracking eye movements to understand better the differences between healthy volunteers and multiple TBI people, and then also to use MRIs to look for injury to white matter pathways that connect to various centers in the brain that are involved in eye movement control as well as the vestibular control. And as an adjunct to this, looking at behavioral dysfunction in these individuals as well because we're trying to see what correlation might exist there.

Thomas Flaig 

So we've been talking different types of things, space travel with an astronaut cohort, Graves disease, but for TBI, it would seem like there's many different patient populations, right? There's a military population, there's perhaps automobile or that sort of situation. There's sporting events with multiple. Do you look at these as different TBI types of inducing injury and does that interplay with the way you think about it or research it?

Prem Subramanian 

I do. And the main focus of our research right now has been on multiply injured veterans. But we have looked at elite athletes as well, have not in our work looked as much at the civilian population. I think the civilian population, it's obviously a broader population age-wise as well as health comorbidity-wise. So it's a little harder there to try to develop some of these connections. So that's, I think, why we've focused more on the military also just with the background and interests that we've had.

But you're absolutely right that the mechanism of injury might have something to do with it as well, because a lot of the military folks are injured by blast trauma. Others are more a blunt-force trauma. And there have been some comparisons in the military population looking at differences between blast and non-blast TBI, and the differences are fewer than we actually thought they might be. So that's been reassuring to us that by looking at the blast population, it may be more broadly applicable to civilians and to others who experience TBI for other reasons.

Thomas Flaig 

So appreciate the work you're doing with veterans and those in the military. And just as a general observation, as I see patients and just talk to people, there's more interest in brain injuries. Whether it's sporting, whether that's civilian life in different ways, or our military folks, there's a lot more interest. So I think it's really important to do this research. And I think what you're saying is it's more complex to research some of these entities.

Prem Subramanian 

It is. And for better or worse, the interest in TBI and brain injury more broadly has brought a lot of people out of the woodwork who have suggested that there are various therapies or diets or other things that might help people with brain injury. And those injured people are really interested, of course, to do whatever they can. And I think the science behind some of what is being touted is not as great as it should be. And one of the reasons we're doing our work is to try to put better science behind it because there are people who suggest that eye movement training and things like this can help people after TBI. And while there is, again, some evidence, there's some evidence that it doesn't work, and we're really trying to figure out who's going to benefit from these treatments. Who wouldn't benefit from these treatments? Can we predict ahead of time so that we don't waste our patient's time, we don't waste money, we don't waste effort, and we really focus therapies on people who are most likely to benefit from them?

Thomas Flaig 

That's such an important point.

Chris Casey 

And could you explain Prem, what the differences between, and this is another condition I believe that could have life-threatening consequences, you can correct me if I'm wrong, but difference between papilledema, if I'm pronouncing it correctly, and pseudopapilledema. I totally butchered that. And why is that an important research topic?

Prem Subramanian 

It's a really important question because papilledema is true swelling of the optic nerve from elevated intracranial pressure. And probably the worst thing that can do that is a brain tumor that raises the pressure in your head. Pseudopapilledema, as you might imagine by the name, is when someone's optic nerve looks like it's swollen, but it's not really. It's just elevated or it has something called optic disc drusen or some other element that fools you into thinking it's swollen. It's a really important question because you want to recognize those people with papilledema and evaluate them for why they have that problem. You don't want to over-test people with pseudopapilledema and subject them to potentially invasive tests like spinal taps to measure their spinal pressure if they don't need it. So it's been an area of research to try to better able to distinguish these two populations of people because it's a lot harder than you think it should be.

And so just a clinical exam isn't enough. And so we have done work, and I have collaborators around the world actually who I've worked with, a former fellow who is in Tehran, who has really worked with me a lot on this with using imaging technology that allows us to look in more depth at literally and figuratively at the optic nerve and to see what's going on behind the nerve. Are there things, clues that we can find findings that are there that really help us to discriminate these two clinical entities. And often the patient walks in the door, they get diagnosed with this, they don't even know they have it, and then all of a sudden you have to decide, is this something potentially life-threatening or is it just the way they've been their whole life?

Chris Casey 

And strabismus is another area you've done some research, especially through the Sue Anschutz Rodgers Eye Center, I understand in fact opening an adult strabismus clinic recently. Could you talk about that and what the causes of strabismus are?

Prem Subramanian 

Strabismus is the generic medical term for misaligned eyes. We hit on a little bit before with thyroid eye disease as being one of the reasons why adults might develop misaligned eyes and double vision. There are a lot of different causes. People can, as a result, just of age or vascular disease, develop problems with the nerves that come to the extraocular muscles, and so the muscle doesn't work properly and their eyes become misaligned. Some adults may have had a tendency towards strabismus or double vision from childhood. It was controlled by their brain for most of their life, but then the brain stops compensating for it, and now they develop this problem. Or they can have trauma, trauma to the orbits, strain trauma can injure muscles or nerves and then lead to strabismus.

So there are a lot of different causes for which adults can then experience double vision and strabismus. What we intended to do or intend to do with our adult strabismus clinic is to harness the expertise of those of us from the neuro-ophthalmology side who take care of these patients and do surgery on them as well as patients from our pediatric ophthalmology side, because pediatric ophthalmologists take care of many, many more children with these kinds of problems, but some of them have expertise and interest in taking care of adults as well. So we're bringing together the doctors from these two different divisions of ophthalmology and giving better access to our patients and having a more unified approach to using our expertise to help them to recover from their strabismus to get usually a surgical cure to their double vision.

Chris Casey 

So you have a lot going on, both with the project Polaris Dawn to your more terrestrial based research. So could you just put in a nutshell, maybe Prem, what you're most excited about as we enter 2025 here?

Prem Subramanian 

I'm really excited more generally in the field of neuro-ophthalmology about advances that we're making therapeutically to help patients in these different areas. So you mentioned one of the things that I try to do is come up with better therapies for people with these different diseases. When I started in neuro-ophthalmology a few years back, we didn't have nearly as much to treat our patients. In fact, we were sometimes accused of simply admiring disease and not doing anything for it.

Now we have better medical interventions. I talked about better understanding of thyroid eye disease. We have better understanding of inflammatory optic neuropathies and better surgery. So what I'm excited about in 2025 is taking some of that, but then leveraging work that we've done in AI to then improve our ability to diagnose and spread our expertise farther. As you might imagine, there are not a lot of neuro-ophthalmologists in the world, but there are a lot of patients who could benefit from the things we do. And using more of the technology to reach them and to help them get access to the kinds of expertise that we have and the care that we can provide is a big part of what I'm looking forward to.

Thomas Flaig 

What a pleasure to visit with a great neuro-ophthalmologist today, learn more about your research and the ways that you're using that research to impact patient outcomes. Really a privilege, and what a great conversation.

Prem Subramanian 

Thank you for having me here today.

Chris Casey 

I've got one last question. I'm just curious, given that you've done so much research associated with astronauts, would you like to travel through space yourself at some point?

Prem Subramanian 

Traveling to space would be pretty cool, but I think it would have to be for a short period of time. I am somewhat claustrophobic, so sticking me in a space capsule for months would probably not be the best idea.

Chris Casey 

Same. To me, that would be the biggest drawback of the whole thing. Yeah, the claustrophobic side. Yeah.

Thomas Flaig 

It's fascinating. Who knows what the future holds for us? And I tell you, understanding the effects in our bodies will be a key part of the decision if we have that opportunity someday, a lot of us.

Chris Casey 

Yeah. So thank you for leading and contributing to the advancements in all of these myriad, very fascinating ways, Prem, and thank you for joining us here today.

Prem Subramanian 

Thanks again.