Layer-specific choroidal vascular adaptation to high-altitude hypoxia revealed by functional OCT at 3,800 m

Ascent to high-altitude induces systemic and ocular changes that alter vision. The functional responses of the choroidal vasculature at different depths to hypoxia remain incompletely understood. In this study, we used functional optical coherence tomography (f-OCT) to quantify changes in choroidal vascular perfusion density (VPD) across superficial, deep, and total choroidal layers in 16 healthy participants. Imaging was performed at baseline (1,100 m) and during acute (day 2) and prolonged exposure (day 9) to high altitude (3,800 m). Our depth-resolved analysis showed a modest but statistically significant decline in superficial choroidal VPD from baseline to day 2 (P = 0.031; Cohen's d = -0.73). In contrast, both deep and total choroidal VPD increased significantly from baseline to day 2 (P = 0.002 and P = 0.003, respectively; Cohen's d > 0.9). Changes in superficial, deep, and total choroidal VPD persisted from day 2 through day 9 at 3,800 m. [Formula: see text] showed a strong negative correlation with deep choroidal (r = -0.655; P = 0.0003) and total choroid VPD (r = -0.566; P = 0.0014), but no significant correlation was observed with the VPD of the superficial layer (r = 0.018; P = 0.93). The strong correlation between VPD and the stimulus index ([Formula: see text]/[Formula: see text]) in the total choroid suggests that hypoxia-induced vasodilation outweighs hypocapnic vasoconstriction, leading to increased perfusion (r = 0.629; P = 0.0003). These findings suggest that deep choroidal hyperperfusion on ascent to high altitude helps sustain outer retinal oxygenation. Depth-resolved choroid imaging may offer new insights into ocular resilience to environmental challenges and provide a valuable tool to monitor spaceflight-related ocular changes associated with neuro-ocular syndrome.NEW & NOTEWORTHY This study reveals that the human choroid mounts a depth-specific vascular response to high-altitude hypoxia. Rather than showing uniform vasodilation, superficial choroidal perfusion decreases, whereas deep choroidal perfusion increases and remains elevated after prolonged altitude exposure. The strong relationship between deep choroidal perfusion and arterial blood gases suggests that hypoxia-driven vasodilation outweighs hypocapnic vasoconstriction. These data highlight functional OCT as a powerful tool for measuring how physiological stress reshapes ocular vascular function and suggest that combining high-altitude exposure with depth-resolved functional OCT may provide a useful terrestrial model for vascular changes relevant to spaceflight-associated neuro-ocular syndrome.