Countermeasures for Visual Impairment in Astronauts

The visual impairment observed in many astronauts after long duration spaceflight aboard the International Space Station is considered the most important mission-threatening medical problem identified in the last decade of the space program. Between 2012 and 2014, NASA and NSBRI have spent $3-4 million/year investigating the clinical course and underlying mechanisms of this condition, termed the Visual Impairment Intracranial Pressure Syndrome (VIIP) because of its theoretical association with elevated intracranial pressure and central venous pressure. During the previous funding cycle, the investigators for this application performed the first invasive measures of intracranial pressure during acute (head down tilt bedrest and parabolic flight) and chronic (24 hours HDT bedrest) changes in gravitational gradients simulating spaceflight in healthy humans. Novel observations made from those studies determined that 1) there is a large range of central venous pressure experienced normally during changes in posture in daily life; 2) these changes occur within seconds of postural transients from upright to supine and then are stable over time in that position; 3) with acute assumption of simulated microgravity (HDT bedrest), intracranial pressure and central venous pressure goes up slightly from the supine position, but over the next 24 hours, returns toward, and sometimes below the supine value because of spatial compensation within the brain; 4) during true microgravity (parabolic flight), the acute reduction in central venous pressure reduces cerebral outflow resistance and ICP decreases compared to the supine position, though remains above the upright position in 1G.

The current hypothesis is that the VIIP syndrome is Not due to a pathologically elevated central venous or intracranial pressure. However, because there is not the usual reduction in pressure typically seen in the upright position on earth, the incessant, low level elevation in ICP (i.e., greater than upright, but less than supine) leads to adaptive changes in the eye which ultimately result in globe flattening, choroidal folds, and visual impairment. Preliminary data suggest that the use of lower body negative pressure (LBNP) can lower ICP while in the head down position, towards the values observed upright. The investigators propose that applying LBNP during sleep in space would be a practical strategy to restore a relevant (though reversed) circadian variability in central venous pressure that would then prevent adaptive changes in the eye. The investigators propose the following hypothesis:

Hypothesis 1: Repeated administration of LBNP at night will cause a safe, sustained reduction in central venous pressure while asleep. This restoration of effective circadian variability in central venous pressure will prevent structural changes in the eye induced by microgravity. To test this hypothesis, the long-term efficacy of nightly LBNP (6-8 hrs) to simulate the upright position and prevent structural changes in the eye during four days of bedrest. Comprehensive, non-invasive state-of-the-art imaging will be used to examine the structure of the visual apparatus, using optical coherence tomography combined with invasive direct measurement of CVP.