Abstract
PURPOSE: To evaluate cephalad fluid shift countermeasures (CMs) as well as optic nerve structure and vasculature in a strict and chronic head-down tilt bedrest (HDTBR) model of Spaceflight-Associated Neuro-ocular Syndrome (SANS). DESIGN: A prospective randomized interventional study. PARTICIPANTS: Forty-seven subjects. METHODS: An HDTBR study was performed with 4 groups. One group underwent 30 days of strict HDTBR. The remaining groups did the same with one of three fluid shift CMs: lower body negative pressure, exercise with veno-constrictive thigh cuffs (EX + CUFF), or intermittent upright posture (all groups, n = 11-12). All subjects underwent testing pre-BR, in HDTBR, and after returning to an upright posture. Ocular tests included optical coherence tomography (OCT), OCT-angiography, multicolor imaging, and intravenous fluorescein angiography. Total retinal thickness 250 microns away from Bruch's membrane opening (TRT250) was measured using a National Aeronautics and Space Administration-defined convention of ∆TRT250 > 20 μm as OCT-determined disc edema in SANS. RESULTS: Only the upright posture (which intermittently reverses headward fluid shifts) resulted in a ∆TRT250 of <20 microns (18.6 ± 5.5 μm; mean ± 95% CI). The remaining three groups (including two CMs) showed a ∆TRT250 of > 20 microns with no differences between groups. As a result, all subjects were then combined. Pre-HDTBR cup width, depth, and volume were associated with increasing ∆TRT250 (P = .001-.002). Increasing ∆TRT250 was associated with both increasing optic nerve hyperfluorescence on intravenous fluorescein angiography (P < .001-.002) and decreasing peripapillary perfusion density on OCT-angiography (P = .04). DISCUSSION: Upright posture is the first SANS CM to show a ∆TRT250 less than the National Aeronautics and Space Administration threshold for optic disc change in this HDTBR Earth-bound analogue of SANS, supporting the headward fluid-shift hypothesis in SANS. The inability to distinguish between the other conditions may have been due to risk factors that are not fully understood. This includes the risk factor of a smaller baseline optic nerve cup, which is associated with SANS-like changes in this study, and as previously shown in astronauts. Finally, the presence of optic disc vascular alterations (increased hyperfluorescence and decreased peripapillary perfusion density), which are also observed in Earth-bound disc edemas, highlights that optic nerve vascular damage is occurring.