Analysis of Retinal Segmentation Changes at High Altitude With and Without Acetazolamide

Our aim was to assess retinal venous diameter and segmented retinal layer thickness variation in acute systemic hypoxia with and without acetazolamide and to relate these changes to high altitude headache (HAH), as a proxy for intracerebral pathophysiology.

A total of 20 subjects participated in a 4-day ascent to the Margherita Hut (4,559 m) on Monte Rosa in the Italian Alps. Each participant was randomized to either oral acetazolamide 250 mg twice daily or placebo. A combination of digital imaging and optical coherence tomography was used to measure retinal vessel diameter and retinal layer thickness. Clinically-assessed HAH was recorded.

A total of 18 participants had usable digital and OCT images, with 12 developing HAH. Significant thickening was seen only in the two inner layers of the retina, the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) at P = 0.012 and P = 0.010, respectively, independent of acetazolamide. There was a significant positive correlation between HAH and both retinal venous diameter (T = 4.953, P = 0.001) and retinal artery diameter (T = 2.865, P = 0.015), with both unaffected by acetazolamide (F = 0.439, P = 0.518).

Retinal venous diameter correlates positively with HAH, adding further evidence for the proposed venous outflow limitation mechanism. The inner layers of the retina swelled disproportionately when compared to the outer layers under conditions of systemic hypoxia. Acetazolamide does not appear to influence altitudinal changes of retinal layers and vasculature.