Effect of chronic high-altitude hypoxia on retinal vascular phenotype, choroidal and retinal vasoreactivity in...

High-altitude chronic hypoxia can induce excessive erythrocytosis (EE, defined as a haemoglobin concentration of ≥21 g/dL in men), leading to hyperviscosity and promoting endothelial dysfunction. We aimed to assess whether EE affects the retinal vascular phenotype and the ophthalmological vascular response to CO₂. We conducted an ophthalmological cross-sectional study among highlanders permanently living at 5100 m (La Rinconada, Peru). The central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE) and retinal vessel tortuosity were measured using semi-automatic imaging software (VAMPIRE) from the diameters of the six largest arteries and veins on fundus images. Choroidal blood flow was assessed using laser Doppler flowmetry. Measurements were performed at rest and during a hypercapnic challenge (+10.1 ± 1.4 mmHg end-tidal CO₂)_. Among the 62 included highlanders, 38 (61%) had EE. Compared with non-EE, highlanders with EE exhibited higher CRVE (278 ± 25 vs. 249 ± 24 µm, P < 0.001), with no other significant ophthalmological differences. Resting CRVE was significantly correlated (all P-values < 0.001) with haematocrit (r = 0.56), haemoglobin concentration (r = 0.65), blood volume (r = 0.55) and the arterial partial pressure of carbon dioxide (r = 0.46). Hypercapnia led to a moderate overall decrease in CRVE (-8.6 ± 22.0 µm, P = 0.02), without a specific effect of EE, and induced no other retinal vascular or choroidal blood flow changes in either group. We observed larger retinal vein diameters in EE highlanders compared with non-EE. Although hypercapnia is known to increase retinal vessel diameter in healthy lowlanders, it selectively decreased CRVE in highlanders, irrespective of EE status. These findings suggest a retinal vascular dysfunction in highlanders, probably induced by chronic exposure to severe hypoxia.