Imagine being on a mission to Mars, and suddenly finding yourself unable to read the ship's instruction manual. Sounds like a nightmare, but in the past few years, the scientists who study astronauts have made a startling discovery: Some of them experience bizarre, unexplained vision problems when they fly into space. Their eyesight might get muddier, and they might start to need glasses where they didn't before. An eye exam could reveal cotton wool spots, or an unexplained swelling or a flattening at the back of their eyeballs.
A decade ago, nobody realized that vision loss in space was even an issue; it wasn't on the radar at all. Now, as we've flown more humans into space, for longer and longer stretches of time, it's become clear just how serious of a problem this is. Many scientists now consider vision loss and other related changes to be the number one risk of spaceflight.
The trouble is, while there are plenty of theories, nobody has a solid explanation for why it happens—and only to some astronauts. Right now, it's impossible to know for sure who will be affected before they fly.
One NASA researcher is staking his reputation on an admittedly far-out hypothesis. If he's right, it could unravel the mystery, and pave the way for new treatments to ensure that astronauts of the future don't struggle this way. It might also have important implications for a group of patients here on Earth, who don't always have a lot of options today.
But the idea is pretty wacky. "When we first came up with this, we were very reluctant to say it out loud. Just because it's that big of a leap," Scott M. Smith, who's led the Nutritional Biochemistry Laboratory at NASA's Johnson Space Center for over 20 years, told me in an interview. (Smith has been studying vision problems in astronauts for the last six years.) "The more we poke at it, the more pieces of the puzzle keep falling in line."
Smith now speculates that astronauts who develop vision problems in space might have an underlying health condition, one that's actually fairly common on Earth: Polycystic ovary syndrome, or PCOS, which affects about one in ten women, according to one estimate, and lasts over a lifetime. He's about to start a clinical trial, with the Mayo Clinic in Minnesota, to study this more.
There's just one problem, and it's a big one: PCOS, of course, only affects women. And all the astronauts who've reported troubles with their eyesight in space, so far at least, have been men.
Astronaut Robert Thirsk lived aboard the International Space Station in 2009 for six months, becoming the first Canadian to do a long-duration mission. He and NASA's Michael Barratt started noticing some changes to their eyesight. Both doctors, they performed ultrasounds on their eyeballs (there's a machine aboard the ISS) and noticed something strange: the backs of their eyeballs had become "flattened, pushed in," as Thirsk told me in one of our previous conversations.
Thirsk became farsighted, and it persisted after he got home, although his vision has slowly improved since then. Other astronauts have reported the same.
NASA astronaut John Phillips, who flew in 2005, recently described to the Washington Post how his vision dropped from 20/20 to 20/100 after six months on the Station. While his vision has improved, he still needs glasses today.
"Some [who experience vision problems] eventually go back to normal," Smith told me. "Others have been followed for years, and they don't go back." He hesitated to even estimate how many astronauts are affected, because the data is so new that we don't know what's typical. "There's a debate over that," he said. "I don't give out a percentage."
Scientists are running experiments on the ISS to figure out what's going on, and have made vision a priority for research. Eye exams are standard for astronauts before, during, and after flight. One popular hypothesis is that a shift in intracranial pressure is to blame: In zero gravity, the fluids in our bodies move upwards, and push on the optic nerve and the back of the eye.
"Everybody is looking into the cardiovascular pathway," Smith told me. "Our group takes a different approach." His research is showing that PCOS patients share some surprising commonalities with this subset of astronauts. In a 2012 study, for starters, Smith described how astronauts who experience vision changes have higher levels of homocysteine in their blood (an amino acid that's a common marker of cardiovascular disease), which is also seen in women with PCOS. But his findings now go beyond that.
Smith's proposed link to PCOS comes out of left field. We still don't know a lot about this mysterious syndrome, not even what causes it, although it's likely some mix of genetics and environment. It's diagnosed in women basically "by exclusion," which means ruling out everything else, as Dr. Sheila Laredo, endocrinologist at Women's College Hospital in Toronto, told me in an interview. (She isn't involved with Smith's work.) Doctors look for certain telltale signs, like irregular or missed periods, a surplus of male hormone, and evidence of "large, visible follicles" on the ovaries, she said.
There's no cure, but there are ways to control it, such as by taking birth control pills to help regulate hormones. Still, patients can struggle with fertility issues and other troubles.
Women with PCOS are often obese, but not always, Laredo said. And they tend to have insulin resistance, which can increase the risk of diabetes, she continued—which can lead to vision problems. "Cotton wool spots are related to poor diabetes control," she said.
Still, eyesight problems are not thought to be directly associated with PCOS, Laredo told me.
When I described Smith's hypothesis about astronauts to Laredo, who estimates that she probably treats the most PCOS patients in her clinic anywhere in Canada, she was startled. "I haven't heard about this at all," she said. "It hasn't hit the PCOS literature."
Depending on the results of the upcoming clinical trial, that may change.
It was last summer when Smith and his small team first started wondering about a link. Preparing some research on genetic similarities in astronauts who suffer from vision issues, they were sifting through the literature, "and realized there's a clinical population that has many of the characteristics, that are exactly like either what we've seen in astronauts with vision issues, or what we hypothesize exists in this group," he said.
"The group we're talking about is women with PCOS," Smith added.
Their paper was published in The FASEB Journal in January, and floats a possible link to PCOS, but almost as an afterthought, close to the end. In the paper, Smith and his team describe genetic differences relating to something called the one-carbon pathway of metabolism—a variation shared by women with PCOS. They also explain how women with PCOS, like these astronauts, have higher levels of homocysteine, altered hormone levels, a thicker retinal nerve fiber layer, intracranial hypertension, the list goes on.
"Although PCOS obviously only affects women, PCOS-type manifestations are not limited to women," the paper says. "Evidence shows that male relatives of PCOS patients have similar symptoms, and some researchers have hypothesized that PCOS occurs in men," it continues, adding that the polycystic ovaries that are the actual namesake of this disease could just be a "downstream effect" of other disruptions, which are shared by both genders.
Anyway, only 80 percent of women with PCOS actually have polycystic ovaries. It's a syndrome we still don't understand, with a name that doesn't accurately describe it.
"Some have suggested that men get PCOS, but are not diagnosed with it because they don't have ovaries," Smith told me in a follow-up email.
Only 11 percent of all humans who've been to space have been women
If PCOS is relatively common among women, with one-in-ten-affected, this raises another question: Why haven't any female astronauts reported vision problems as a result of flying in space?
For one thing, all astronauts are heavily screened before they're allowed to begin training. Women with PCOS tend to be obese, or show insulin resistance, which would likely exclude them from flying. "We speculate that this may be why we're not seeing [vision loss] in female astronauts. They're not being selected because tests are excluding them," Smith said.
That, and we just haven't flown nearly as many women into space as men. Only 11 percent of all humans who've been to space have been women. Maybe if more of them made it onto Station, these problems would start to crop up in women, too.
"I'd say, based on the theory, if we were to fly women with PCOS into space, they'd all develop these vision issues," Smith said.
At the Mayo Clinic, researchers will soon begin recruiting women to participate in a clinical trial. They're hoping for 80 altogether, divided into four groups, including women with PCOS, with intracranial hypertension (an unexplained increased pressure in the skull, that also affects many women with PCOS, and is known to cause vision changes), and a healthy control. They'll be collecting data and comparing it to as many astronauts as they possibly can, both male and female—already, 49 astronauts were included in the January study.
I talked to Dr. Alice Chang, an endocrinologist at the Mayo Clinic who is principal investigator of this particular trial, and working with Smith. When he approached the clinic about doing it, "it was a little embarrassing, as a PCOS researcher, that [vision changes] were not at the forefront of our minds," she told me. Doctors screen these women for all kinds of things, from sleep apnea to pre-diabetes, but don't necessarily look for changes in their eyesight.
Depending on what comes out of this clinical trial, maybe that will change in the future.
As for whether PCOS could affect both sexes—not just women—Chang became thoughtful. "The name of the syndrome has been misleading," she said. "We get distracted by it." In reality, she said, this condition is more about having an excess of testosterone-like hormone, which can impact fertility and cause the downstream effects we see in PCOS.
So, yes, it's possible that men do experience a version of it.
Smith's research stands to help these patients, a group he probably never imagined would benefit when he started trying to figure out the root causes of astronaut vision loss.
The PCOS patients, meanwhile, could help humans fly more safely in space. Just as scientists do bedrest studies to get an idea about what zero gravity does to our bodies, Smith said, "we feel that women with PCOS might be a matching analog for these astronauts."
Photo above: Expedition 47 Commander Tim Kopra of NASA participates in the Ocular Health investigation aboard the International Space Station. The study seeks to help researchers better understand microgravity-induced visual impairment and changes believed to arise from elevated intracranial pressure.