Repeat Exposures to Spaceflight or Bed Rest and Spaceflight-Associated Neuro-Ocular Syndrome Findings

Importance: Crewmembers on long-duration spaceflight missions are at risk of developing mild to moderate optic disc edema and ventricular volume expansion. The effect of repeat exposures on ocular and brain tissues is unknown and needs to be better understood for astronauts flying multiple missions. Objective: To evaluate whether a second exposure to spaceflight or a spaceflight analog is associated with larger changes in optic disc edema or brain ventricular volume expansion. Design, Setting, and Participants: Peripapillary total retinal thickness (TRT) extending from the Bruch membrane opening to 250 µm was quantified using optical coherence tomography imaging before and during spaceflight or the spaceflight analog head-down tilt bed rest (HDTBR). Magnetic resonance imaging was performed before and after spaceflight or HDTBR to quantify changes in brain volumetrics. Included were astronauts and participants in HDTBR from the International Space Station or German Aerospace Center :envihab facility. Study data were analyzed from November to December 2025. Exposures: Two spaceflight missions of approximately 6 months or 2 HDTBR campaigns of 30 to 60 days in duration. Main Outcomes and Measures: The change in TRT (∆TRT) from preflight/pre-HDTBR to approximately 30 days before return to Earth or 30 days into HDTBR and the change in lateral ventricular volume (∆LVV) from preexposure to postexposure. Data were analyzed to determine if repeat exposure to spaceflight or HDTBR augmented the magnitude of change from the first exposure to the second. Results: This study included a total of 7 astronauts (mean [SD] age, 43 [5] years; 5 male [71%]) and 5 participants in HDTBR (mean [SD] age, 35 [9] years; 3 male [60%]). ΔTRT was not different between spaceflight missions (mean difference, -5.6 µm; 95% CI, -15 to 3.7 µm; P = .23) or between HDTBR campaigns (mean difference, 3.1 µm; 95% CI, -3.3 to 9.5 µm; P = .33). ΔLVV was not different between spaceflight missions (mean difference, 0.1 mL; 95% CI, -0.9 to 1.1 mL; P = .78). The 3 participants in HDTBR with magnetic resonance imaging data presented with a similar ΔLVV after each campaign (0.4 vs 0.1, 1.1 vs 0.4, and 0.9 vs -0.2 mL, respectively). Conclusions and Relevance: Findings of this case series show that a single repeat exposure to HDTBR or spaceflight did not appear to be associated with an increase in the magnitude of change in ocular or brain structures. Whether these exposures are additive in causing increased long-term functional changes remains unknown. These findings may be used by the space medicine community to guide the prediction of changes that might occur in those who undertake multiple spaceflight missions.