Exploring the galaxy has long been one of mankind's greatest ambitions. But extraordinary voyages sometimes come with extraordinary price tags. And we're not talking about invoices from Elon Musk.

Long-duration spaceflight has given rise to a unique medical diagnosis not seen on Earth: spaceflight associated neuro-ocular syndrome (SANS).

"Individuals affected by spaceflight associated neuro-ocular syndrome become more far-sighted and have trouble seeing things close up, which can be anticipated and mitigated with glasses," said Dr. Andrew Lee, chair of Ophthalmology at Houston Methodist and a consulting physician for astronauts with the condition. "However, there's still a lot we don't know about SANS, including the precise cause, risk factors and countermeasures, why it impacts some people and not others, and whether it's a sign that something more serious is going on."

A top research priority

The condition is difficult to study because the sample size is tiny, and it only occurs in microgravity, making evaluations performed on Earth less relevant. Tests such as MRI and spinal tap could reveal useful information, but scientists haven't figured out how to safely perform them in space.

Despite the earthbound obstacles, Dr. Lee is leading the research effort to better understand the mysterious syndrome, which could ground NASA's plans for travelling to Mars before they get a chance to lift off. The research, a joint venture by Houston Methodist and NASA, aims to predict, monitor, treat and hopefully prevent SANS.

"It's important to figure this out because SANS is a dose-dependent phenomenon, meaning the longer you're in space, the more substantial the risk," said Dr. Lee. "A round trip crewed mission to Mars is likely to take up to 2 to 2.5 years, longer than a typical tour of duty on the International Space Station. We don't know the impact of such a long deployment."

Understanding microgravity's effects

Believed to be the result of weightlessness redistributing fluids within the body and causing increased pressure in the head and swelling behind the eyes, SANS affects the eyesight of about 70% of astronauts who spend an extended amount of time (>6 months) in space.

The constellation of neuro-ophthalmic symptoms associated with SANS includes optic disc edema, globe flattening, retinal and choroidal folds, hyperopic refractive error shifts and cotton wool spots.

Although no astronauts have experienced significant, permanent loss of vision so far, the effects of SANS are believed to be cumulative. Some conditions — choroidal folds and hyperopic refractive shifts, for instance — can persist even after the astronauts return to Earth and its normal gravitational environment.

"Our big fear is that the vision issue is a warning sign of other, more serious health effects," Dr. Lee explained. "Human bodies evolved for life on Earth, where everything stays in place because it's constantly being pulled toward the ground."

Head-down tilt bed rest studies

Because astronaut research is limited by the small sample size of humans undergoing long-duration spaceflight, identifying a terrestrial experimental model of SANS is imperative to facilitate its study and test possible preventative measures and treatments.

"On Earth, we don't have a good way to replicate zero gravity or the cephalad fluid shift that occurs in space," said Dr. Lee. "The closest analogy we have are head-down tilt bed rest (HDTBR) studies, which require participants to lie down in a bed, sometimes for months at a time."

Because of this requirement, HDTBR studies also suffer from small sample sizes. In addition, a recent study found that while some SANS findings are observed in study participants, others are not, suggesting that HDTBR is a close but imperfect model for SANS.

"Head-down tilt studies remain ongoing, however, and have been really helpful in the identification of other key risk factors, including genetic traits that may predispose astronauts to SANS," Dr. Lee said. "The current research also helps us look at the effectiveness of potential countermeasures for SANS, such as a lower body negative pressure device, which is technology that currently exists on the ISS."

HDTBR has also been leveraged to identify better ways to monitor SANS. Since invasive intracranial pressure measurements like lumbar puncture are currently not feasible on the ISS, HDTBR studies have been able to test some non-invasive measures like otoacoustic emissions probes, which measure changes in the positioning and tension of the middle ear, as a potential tool for measuring intracranial pressure in space.

To infinity and beyond

"We have also looked at developing a portable goggles-based device that would allow us to create virtual and real measurements of astronauts during space flight," Dr. Lee said, noting that such a device would eventually have terrestrial patient care applications as well.

Meanwhile, the researchers are working to leverage artificial intelligence to help monitor and assist with any urgent medical issues that arise, because communication delays will be significant between the Earth and Mars.

Dr. Lee's extensive body of research recently led to the publication of the first textbook on spaceflight associated neuro-ocular syndrome.

"It's weird to write a book on a condition I will never see on Earth or be able to observe face-to-face on a spacecraft in an astronaut," Dr. Lee said. "But that is one of the many benefits of working here at Houston Methodist. We get to partner with extraordinary people to study something completely unique that could pave the way for future interplanetary travel. Doesn't get much cooler than that."