Dynamic changes in ocular and retinal function across acute hypobaric hypoxia

Visual impairment and intracranial pressure (VIIP) syndrome has been recognized as a major health risk during long-duration spaceflight, but the underlying mechanisms remain incompletely understood. Terrestrial high-altitude hypoxia provides a relevant analog to investigate these processes. In this study, 39 healthy participants were evaluated at baseline (sea level) and during acute exposure to 3500 m, 4000 m, and 4500 m. Measurements included refraction [sphere (SPH), cylinder (CYL)], intraocular pressure (IOP), and electroretinography (ERG). The results demonstrated subtle, non-significant fluctuations in refraction and IOP across different altitudes. ERG responses showed a reduction in amplitude and an increase in latency, especially a significant reduction in the amplitude of the flicker b-wave, suggesting that the inner retinal layer is extremely sensitive to hypoxia. Regression analyses identified a significant negative association between IOP and flicker B-wave amplitude (β = -0.307, p = 0.031), whereas no significant associations were found between refractive status and ERG parameters. These findings suggest that acute hypoxic exposure affects retinal function while subtly altering ocular optics, reflecting aspects of the VIIP syndrome and acute mountain sickness (AMS). Therefore, our findings provide a rationale for future validation of noninvasive ocular measurements, including refraction and ERG, as candidate biomarkers for hypoxia-related visual and neurological risk in both high-altitude and spaceflight environments.