HRR - Risk - Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS)

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Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS)

Short Title: SANS Last Published: 04/26/21 11:45:34 AM (Central)

Element: Human Health Countermeasures (HHC)

Evidence: Report

Risk Master Logic Diagram: Not Available

Point of Contact: Steve Laurie

HRP Risk Status: Active [current research ongoing]

Risk Ratings and Dispositions per Design Reference Mission (DRM) Category

DRM Categories	Mission Type and Duration	Operations		Long-Term Health
DRM Categories	Mission Type and Duration	LxC	Risk Disposition *	LxC	Risk Disposition *
Low Earth Orbit	Short (<30 days)	3x1	Accepted	3x2	Accepted
Low Earth Orbit	Long (30 days-1 year)	3x2	Accepted	3x3	Accepted
Lunar Orbital	Short (<30 days)	3x1	Accepted	3x2	Accepted
Lunar Orbital	Long (30 days-1 year)	3x2	Accepted	3x3	Accepted
Lunar Orbital + Surface	Short (<30 days)	3x1	Accepted	3x2	Accepted
Lunar Orbital + Surface	Long (30 days-1 year)	3x2	Accepted	3x2	Accepted
Mars	Preparatory (<1 year)	3x2	Accepted	3x3	Accepted
Mars	Mars Planetary (730-1224 days)	3x4	Requires Mitigation	3x4	Requires Mitigation
Note: LxC is the likelihood and consequence rating. The information above was last approved by the Human System Risk Board in 4/2020.

Risk Statement

Given that ocular and brain structural changes develop during spaceflight, there is a possibility that these changes could lead to short-term or long-term vision alterations, cognitive effects, or other deleterious health effects.

HSRB State of Knowledge

The Risk Context section in the HRR is no longer applicable for this risk based on the last updated date. The content is maintained within other sections of the HSRB risk record.

Mitigation Strategy

The Human Research Program (HRP) is dedicated to discovering the best methods and technologies to determine the cause and contributing factors to SANS, as well as developing strategies and countermeasures to prevent or mitigate SANS. Space Medicine Operations manages the risk from a clinical perspective. Since 2009, medical surveillance has expanded and includes comprehensive pre-, in-, and postflight assessment of ocular parameters, including optical coherence tomography (OCT) images, ocular ultrasound, ophthalmic imaging, and visual acuity testing. Ultimately, the goal of both Space Medicine Operations and HRP is to identify and implement a set of preventative and/or countermeasures for SANS. There is a multifaceted research approach that aims to determine the underlying risk factors for developing SANS, to test possible countermeasures to prevent or reverse it, and to identify potential long-term health outcomes resulting from SANS findings. Findings from this research will be used to inform mitigation strategies.

Research is currently being conducted through retrospective data sharing to conduct advanced novel quantitative analyses and identify correlations among the SANS signs and symptoms. Studies also include use of modeling to help inform the SANS etiology. Moreover, prospective research studies are being conducted to characterize SANS, which include determining the role of the cephalad fluid shift, identifying potential visual functional changes, tied to the ocular structural findings, investigations to determine relationships between the documented ocular and brain structure changes, and investigating potential genetic or anatomical predisposition to developing SANS. Recently, research findings have provided evidence that the earliest signs of optic disc edema can be detected based on an increase in total retinal thickness measured from optical coherence tomography images. These data suggest ~70% of crew flying 4-6 month long missions to the International Space Station develop early signs of optic disc edema.

Technology currently on ISS to address SANS includes visual acuity testing software, ocular ultrasound, ophthalmic imaging, and optical coherence tomography, including OCT MulitColor Imaging. In addition, research studies include preflight and postflight MRI of the brain and eye. Additional research will focus on following astronauts after return from long-duration ISS missions to determine if any long term visual function deficits develop.

Use of strict head-down tilt bed rest as a ground-based analog of SANS was first established in 2017 and will be used to test potential countermeasures starting in 2021. In addition, parabolic flight studies are planned to characterize acute cephalad venous fluid shifts, including use of a spectrum of gravitational levels to understand if surface operations on the Moon or Mars may reverse the headward fluid shift that occurs in weightlessness. SANS murine ISS experiments will determine the interplay of arterial, venous, and lymphatic alterations, along with contributions of space radiation. Data obtained from these studies will enable closure of these gaps and facilitate SANS countermeasure development. Medical Standards and Clinical Practice Guidelines are used by Space Medicine Operations to protect the safety of the crew, and as research progresses, findings will be transferred to Operations.

Gaps (14)

SANS-101: Determine the relationship between fluid shifts (intravascular, interstitial, CSF) and ocular manifestations in astronauts during spaceflight.

SANS-102: Determine the relationship between the fluid-shifts induced ocular changes and fluid shifts in the CNS, including whether elevated intracranial pressure or brain edema play a role.

SANS-103: Determine whether ground-based induced fluid shifts lead to ocular manifestations.

SANS-104: Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights.

SANS-201: Determine if altered atmospheric conditions (e.g., elevated ambient CO2, mild hypoxia from exploration atmosphere) has a contributing role in the development of ocular manifestations.

SANS-202: Determine if genetic/metabolic/anatomic dispositions and biomarkers, and sex differences have a contributing role in the development of ocular manifestations.

SANS-203: Determine if radiation has a contributing role in the development of ocular manifestations.

SANS-204: Determine if sleep/glymphatics has a contributing role in the development of ocular manifestations.

SANS-301: Develop and test mechanical countermeasures in the laboratory.

SANS-302: Test mechanical countermeasures in a strict bed rest analog.

Ground-Based Flight Analogs	Bedrest [e.g., envihab, other bedrest facilities]
Number of Subjects	10

Ground-Based Flight Analogs	Bedrest [e.g., envihab, other bedrest facilities]
Number of Subjects	24

Ground-Based Flight Analogs	Bedrest [e.g., envihab, other bedrest facilities]
Number of Subjects	12

Ground-Based Flight Analogs	Bedrest [e.g., envihab, other bedrest facilities]
Number of Subjects	12

Ground-Based Flight Analogs	Bedrest [e.g., envihab, other bedrest facilities]
Number of Subjects	15

Specific Aim I

Specific Aim II

Specific Aim III

Ground-Based Flight Analogs	Reduced Gravity Flight
Number of Subjects	8

Ground-Based Flight Analogs	Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO]
Number of Subjects	30