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A multifactorial, evidence-based analysis of pathophysiology in Spaceflight Associated Neuro-Ocular Syndrome (SANS)

Eye volume 39, pages 700–709 (2025)Cite this article

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Abstract

The National Aeronautics and Space Administration (NASA) in the United States has been studying a fascinating and unique constellation of neuro-ophthalmic findings collectively known as Spaceflight Associated Neuro-Ocular Syndrome (SANS). SANS is unique to the space environment of microgravity and produces novel physiological and pathological findings that have no direct terrestrial equivalent. The neuro-ophthalmic phenomenon is a major physiologic barrier to future planetary spaceflight. The underlying pathophysiology of SANS remains ill-defined, but since its initial report in 2011, several hypotheses have been proposed including increased intracranial pressure, cerebral venous congestion and glymphatic stasis, compartmentalization of CSF within the orbital nerve sheath sub-arachnoid space (SAS), upward brain shift, inflammation, disrupted axoplasmic transport, and radiation exposure. These aetiologies may not be mutually exclusive and may be interconnected, leading to an integrative, multifactorial aetiology of SANS. This paper critically analyses the various hypotheses of this neuro-ophthalmic phenomenon and the connections between the physiologic and anatomical evidence-based changes observed in spaceflight and terrestrial analogues. Continued prospective, longitudinal study and development of practical countermeasures for SANS will be necessary for future human spaceflight missions including the mission to Mars.

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Fig. 1: Optical coherence tomography (OCT) of an astronaut pre-flight and 30 days prior to returning from long-duration spaceflight (R-30).
Fig. 2: Multi-colour imaging of an astronaut with spaceflight-associated neuro-ocular syndrome (SANS).
Fig. 3: Flowchart showing possible multifactorial, integrative aetiologies of SANS pathophysiology.

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Authors and Affiliations

  1. Department of Emergency Medicine, Memorial Hermann The Woodlands, The Woodlands, TX, USA

    Laura A. Galdamez

  2. NASA Ophthalmology Consultant, Moab, UT, USA

    Thomas H. Mader

  3. Department of Ophthalmology and Visual Sciences, University of Michigan Kellogg Eye Center, Ann Arbor, MI, USA

    Joshua Ong

  4. Department of Neurology, Houston Methodist Hospital, Houston, TX, USA

    Cihan Mehmet Kadipasaoglu

  5. Department of Ophthalmology, Houston Methodist Hospital, Houston, TX, USA

    Andrew G. Lee

  6. Baylor College of Medicine and the Baylor Center for Space Medicine, Houston, TX, USA

    Andrew G. Lee

  7. Departments of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medicine New York, New York, NY, USA

    Andrew G. Lee

  8. Department of Ophthalmology, The University of Texas Medical Branch (UTMB), Galveston, TX, USA

    Andrew G. Lee

  9. Department of Ophthalmology, The University of Iowa Hospitals and Clinics, Iowa City, IA, USA

    Andrew G. Lee

  10. The UT MD Anderson Cancer Center, Houston, TX, USA

    Andrew G. Lee

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  1. Laura A. Galdamez
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  2. Thomas H. Mader
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  5. Andrew G. Lee
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Contributions

LAG, THM, JO, and AGL wrote the original draft of the manuscript. LAG, THM, JO, CMK, and AGL reviewed and edited the manuscript. All authors reviewed and approved the final manuscript.

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Correspondence to Andrew G. Lee.

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AGL is a consultant for the National Aeronautics and Space Administration (NASA) and serves on the editorial board of Eye.

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Galdamez, L.A., Mader, T.H., Ong, J. et al. A multifactorial, evidence-based analysis of pathophysiology in Spaceflight Associated Neuro-Ocular Syndrome (SANS). Eye 39, 700–709 (2025). https://doi.org/10.1038/s41433-025-03618-3

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