Spaceflight associated neuro-ocular syndrome

Spaceflight-associated neuro-ocular syndrome (SANS) is a collection of distinct findings seen in some astronauts following prolonged spaceflight and is characterized by: optic disc edema, globe flattening, and choroidal folds anemia and SANS ¹⁾.

More than half of astronauts returning from long-duration missions on the International Space Station present with neuro-ocular structural and/or functional changes, including optic disc edema, optic nerve sheath distension, globe flattening, choroidal folds, or hyperopic shifts. This spaceflight-associated neuro-ocular syndrome (SANS) represents a major risk to future exploration class human spaceflight missions, including Mars missions ²⁾

Current in-flight and post-flight imaging modalities (e.g., optical coherence tomography, orbital ultrasound, and funduscopy) have played an instrumental role in the understanding and monitoring of SANS development.

The precise etiology of this neuro-ophthalmic phenomenon is still not completely understood ³⁾.

SANS may be a potential barrier to future deep space missions, and therefore it is critical to further elucidate the underlying pathophysiology for effective countermeasures. The complexity and unique limitations of spaceflight require careful consideration and integration of leading technology to advance our knowledge of this extraterrestrial syndrome. We describe the current neuro-ophthalmic imaging modalities and hypotheses that have improved our current understanding of SANS, discuss newer developments in SANS imaging (including non-invasive near-infrared spectroscopy), and summarize emerging research in the development of an aspirational future head-mounted virtual reality display with multimodal visual assessment technology for the detection of neuro-ocular findings in SANS ⁴⁾.

Although the exact pathophysiology of SANS is unknown, the evidence thus far suggests that an increase in intracranial pressure (ICP) relative to the upright position on Earth, which is due to the loss of hydrostatic pressure gradients in space, may play a leading role ⁵⁾

Laurie et al. exposed healthy subjects (n = 24) to strict 6° head-down tilt bed rest (HDTBR), an analog of weightlessness that generates a sustained headward fluid shift, and monitored for ocular changes similar to findings that develop in Spaceflight associated neuro-ocular syndrome (SANS). Two-thirds of the subjects received daily 30-min exposure to artificial gravity (AG, 1 g at center of mass, ~0.3 g at eye level) during HDTBR by either continuous (cAG, n = 8) or intermittent (iAG, n = 8) short-arm centrifugation to investigate whether this intervention would attenuate headward fluid shift-induced ocular changes. Optical coherence tomography images were acquired to quantify changes in peripapillary total retinal thickness (TRT), retinal nerve fiber layer thickness, and choroidal thickness, and to detect chorioretinal folds. Intraocular pressure (IOP), optical biometry, and standard automated perimetry data were collected. TRT increased by 35.9 µm (95% CI, 19.9-51.9 µm, p < 0.0001), 36.5 µm (95% CI, 4.7-68.2 µm, p = 0.01), and 27.6 µm (95% CI, 8.8-46.3 µm, p = 0.0005) at HDTBR day 58 in the control, cAG, and iAG groups, respectively. Chorioretinal folds developed in six subjects across the groups, despite small increases in IOP. Visual function outcomes did not change. These findings validate strict HDTBR without elevated ambient CO2 as a model for investigating SANS and suggest that a fluid shift reversal of longer duration and/or greater magnitude at the eye may be required to prevent or mitigate SANS ⁶⁾.

During long-term missions, some astronauts experience structural and functional changes of the eyes and brain which resemble signs/symptoms experienced by patients with intracranial hypertension. Weightlessness prevents the normal cerebral volume and pressure “unloading” associated with upright postures on Earth, which may be part of the cerebral and ocular pathophysiology. By placing the lower body in a negative pressure device (LBNP) that pulls fluid away from cranial compartments, Petersen et al. from the Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Department of orthopedic surgery, University of California, San Diego, Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Dallas, Institut für Sportwissenschaft, Universität Innsbruck, Department of Neurosurgery, Rigshospitalet, Copenhagen, Baker Heart and Diabetes Institute, Melbourne, Department of Internal Medicine, Division of Cardiology. University of Colorado Anschutz Medical Campus, Aurora, CO, University of Washington School of Medicine, Departments of Neurology and Neurological Surgery, Seattle, simulated effects of gravity and significantly lowered pressure within the brain parenchyma and ventricle compartments. Application of incremental LBNP demonstrated a non-linear dose-response curve suggesting 20 mmHg LBNP as the optimal level for reducing pressure in brain without impairing cerebral perfusion pressure. This non-invasive method of reducing pressure in the brain holds potential as a countermeasure in space as well as treatment potential for patients on Earth with traumatic brain injury or other pathology leading to intracranial hypertension.

Patients with elevated intracranial pressure (ICP) exhibit neuro-ocular symptoms including headache, papilledema, and loss of vision. Some of these symptoms are also present in astronauts during and after prolonged space-flight where lack of gravitational stress prevents daily lowering of ICP associated with upright posture. Lower body negative pressure (LBNP) simulates the effects of gravity by displacing fluid caudally and we hypothesized that LBNP would lower ICP without compromising cerebral perfusion. Ten cerebrally intact volunteers were included: 6 ambulatory neurosurgical patients with parenchymal ICP-sensors and 4 former cancer patients with Ommaya-reservoirs to the frontal horn of a lateral ventricle. We applied LBNP while recording ICP and blood pressure while supine, and during simulated intracranial hypertension by 15° head-down tilt. LBNP from 0-50 mm Hg at increments of 10 mmHg lowered ICP in a non-linear dose-dependent fashion; when supine (N = 10), ICP was decreased from 15 ± 2 mmHg to 14 ± 4, 12 ± 5, 11 ± 4, 10 ± 3, 9 ± 4, respectively (P < 0.0001). Cerebral perfusion pressure (CPP), calculated as mean arterial blood pressure at midbrain-level minus ICP, was unchanged (from 70 ± 12 mmHg to 67 ± 9, 69 ± 10, 70 ± 12, 72 ± 13, 74 ± 15; P = 0.02). 15° head-down tilt (N = 6) increased ICP to 26 ± 4 mmHg, while application of LBNP lowered ICP (to 21 ± 4, 20 ± 4, 18 ± 4, 17 ± 4, 17 ± 4; P < 0.0001) and increased CPP (P < 0.01). Twenty mmHg LBNP may be the optimal level to lower ICP without impairing CPP to counteract spaceflight associated neuro-ocular syndrome in astronauts. Furthermore, LBNP holds clinical potential as a safe, non-invasive method for lowering ICP and improving CPP for patients with pathologically elevated ICP on Earth ⁷⁾.