Effects of mild hypercapnia and head-down tilt on translaminar pressure and ocular structures in healthy human subjects

Abstract

Purpose : To determine if mild hypercapnia combined with a cephalad fluid shift due to head-down tilt (HDT), a space flight analog, induces ocular changes similar to those reported by astronauts during and after long-duration space flight and if ocular changes are associated with increased intracranial pressure (ICP).

Methods : We conducted 3 1-h trials: 1) seated upright, room air; 2) 6° HDT, room air (HDT); and 3) 6° HDT, breathing 1% CO₂, 21% O₂, 78% N₂ (HDT+CO₂). The seated trial occurred first and the order of HDT and HDT+CO₂ was randomized. Noninvasive ICP (nICP) was estimated using a novel algorithm modeling the middle cerebral artery blood flow velocity (transcranial Doppler ultrasound), arterial blood pressure (Finometer), and ECG. Optic nerve sheath diameter (ONSD) was measured using ultrasound. Spectralis optical coherence tomography imaging of the choroid was acquired with the scanning head custom mounted on a surgical arm to enable imaging during HDT. MATLAB software was developed to analyze choroidal thickness of a 3-mm foveal area from a cross-sectional scan passing through the fovea and optic disc. Intraocular pressure (IOP) was measured using the Icare Pro tonometer. Mixed-effects linear regression modeling was used to assess differences between trials.

Results : Six healthy male subjects have completed the study. During HDT and HDT+CO₂ nICP, ONSD, choroidal thickness, and IOP increased significantly compared to seated (p-values .003 to <.001), but HDT and HDT+CO₂ were not different from each other. Compared to seated (8.5 mm Hg), nICP increased by 6.0 and 5.3 mm Hg during HDT and HDT+CO₂, respectively. ONSD increased from 5.94 mm (seated) to 6.58 (HDT) and 6.55 mm (HDT+CO₂). Choroidal thickness increased by 18.8 and 19.4 µm during HDT and HDT+CO₂, respectively. IOP was statistically elevated during HDT (16.4 mm Hg) and HDT+CO₂ (16.8 mm Hg) compared to seated (15.4 mm Hg). This resulted in a significant fall in translaminar pressure gradient (TPG=IOP-ICP) from 7.0 mm Hg (seated) to 1.9 mm Hg (HDT) and 3.1 mm Hg (HDT+CO₂).

Conclusions : In healthy subjects, HDT increased nICP, ONSD, and choroidal thickness, and led to a fall in TPG; adding mild hypercapnia did not augment these changes. These novel nICP and choroid measurement techniques may help determine if ICP and/or TPG contribute to ocular changes and vision impairment in astronauts as well as glaucoma patients.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.