Sex-Based Differences in Intraocular Pressure During Head-Down Tilt in a Spaceflight Analog Model

INTRODUCTION: Spaceflight-associated neuro-ocular syndrome is a high-priority research gap, especially regarding its mechanisms and individual susceptibility, including sex-based differences. This study investigates sex-specific intraocular pressure (IOP) responses during head-down tilt (HDT) to improve understanding of differential risk profiles and inform the development of targeted countermeasures. METHODS: A total of 15 healthy subjects (8 males, 7 females) completed a 60-min -12° HDT protocol. IOP was measured in a seated baseline condition and at 0, 30, and 60 min during HDT using a rebound tonometer. Blood pressure and heart rate were monitored continuously. Sex-based comparisons were evaluated using repeated measures analysis of variance. RESULTS: Males exhibited a progressive elevation, with mean changes of 2.00 ± 1.51 mmHg at 0 min, 3.50 ± 3.38 mmHg at 30 min, and 5.00 ± 3.12 mmHg at 60 min. In contrast, females showed a biphasic pattern with mean changes of 1.86 ± 2.73 mmHg at 0 min, 3.71 ± 2.75 mmHg at 30 min, and a slightly reduced elevation of 3.29 ± 3.09 mmHg at 60 min. While the overall IOP elevation was comparable between sexes, males demonstrated more sustained increases and females showed early elevation followed by partial recovery. DISCUSSION: These findings suggest that males may be more susceptible to sustained IOP elevations under fluid shift conditions, potentially increasing spaceflight-associated neuro-ocular syndrome risk. In contrast, the IOP modulation in females may reflect sex-specific regulatory mechanisms. These results support future development of personalized countermeasures for spaceflight and may inform adjunctive approaches for terrestrial ocular conditions. Walck CD, Frantz Z, Brattain NJ, Bolger B. Sex-based differences in intraocular pressure during head-down tilt in a spaceflight analog model. Aerosp Med Hum Perform. 2026; 97(2):69-74.