Optic nerve sheath diameter increases during 12◦ head-down tilt in healthy volunteers: a crossover pilot study informing the design of a spaceflight countermeasure trial

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Background Spaceflight-associated neuro-ocular syndrome (SANS) is hypothesized to arise from a headward fluid shift that elevates intracranial pressure and distends the optic nerve sheath. Head-down tilt (HDT) is the ground-based analog of microgravity, and optic nerve sheath diameter (ONSD) measured by transorbital B-mode ultrasound is a candidate non-invasive marker of intracranial pressure. Before a definitive trial in which lower body negative pressure (LBNP) is added to 12 ◦ HDT as a putative countermeasure, we conducted a pilot study to (i) confirm that 12 ◦ HDT detectably elevates ONSD with a high-frequency linear probe, (ii) identify the time of peak response, (iii) optimize the measurement schedule, and (iv) provide effect-size estimates for powering. Methods Eight healthy young participants (4 women, 4 men; mean age 30.9 years) underwent two conditions in a randomized, balanced two-period crossover with a 14-day washout: supine (0 ◦ HDT) and 12 ◦ HDT. Bilateral transorbital B-mode ultrasound was recorded with a 17-MHz linear probe (Philips iU22) at 0, 30, 60, 90, 120, 150, 180, 210 and 240 min. Five frames per clip were measured offline and averaged across both eyes. The primary analysis was a 2-way repeated-measures ANOVA (Condition × Time) with Greenhouse–Geisser correction. Posthoc paired comparisons at each time point used Bonferroni adjustment. Gender was examined in a secondary mixed model. Results The Condition × Time interaction was highly significant ( p GG < 0.001). ONSD did not differ between conditions up to 60 min but was larger under 12 ◦ HDT from 90 min onward, peaking at 150 min with a mean increment of 0.79 mm (95% CI 0.62–0.97), then partially regressing. No gender effect was detected, and baseline ONSD did not differ between visits, consistent with adequate washout. Conclusion A 12 ◦ HDT exposure of ≥ 90 min produces a reproducible, large-magnitude ONSD increase peaking at 150 min in healthy adults; a 0–180 min measurement window is sufficient. These data support a full three-arm crossover trial of LBNP as a candidate countermeasure, with graduated lower-limb compression included as a mechanistic positive control to verify that headward fluid redistribution is the aggravating factor.