Purpose of Review:A growing number of opportunities for paying customers to travel to space are becoming available. Preflight medical screening of these potential private astronauts will likely be performed by local physicians, with referral to specialists in aerospace medicine as required for more in-depth evaluation before flight qualification. Neurologic concerns contribute a portion of the potential medical risks for these private astronauts, especially with the participation of more diversified crews than traditional governmental astronauts. The objective of this article was to review the current knowledge base concerning cerebrovascular adaptation to spaceflight to inform risk factor assessment for flight-associated cerebrovascular emergencies by the neurologic community when performing initial medical screening of potential private astronauts. Recent Findings:A review of published human spaceflight studies and medical guidelines regarding cerebrovascular risks for spaceflight was conducted. Most of the available literature describes cohorts of a small number of astronauts undergoing spaceflight missions of various flight profiles. While there are gaps in the literature, cerebrovascular adaptation to spaceflight occurs, which may alter the medical risk profile in susceptible individuals. The occurrence of an inflight cerebrovascular emergency could have devastating consequences; therefore, additional screening tests may be required, based on risk level and mission profile, in assessing the more diverse commercial spaceflight population expected over the next decade. Summary:With increasing interest in commercial space tourism among diverse participant populations, the stroke risk in microgravity/reduced gravity environments is unknown. Furthermore, stresses of rocket ascent/descent, abnormal fluid dynamics in microgravity, altered atmospheric conditions, and other unknown occupational hazards add additional complexity. Because inflight emergency management protocols have yet to be developed, the most effective tool to ensure spaceflight participant safety is comprehensive preflight preventative screenings. Determining neurologic risk factors is critical for developing evidence-based guidelines for preventative measures and treatment protocols in the future.

BACKGROUND: This article documents the stability of photorefractive keratectomy (PRK) and laser -assisted in situ keratomileusis (LASIK) in two astronauts during 6-mo missions to the International Space Station. CASE REPORTS: Ocular examinations including visual acuity, cycloplegic refraction, slit lamp examination, corneal topography, central corneal thickness, optical biometry (axial length/keratometry), applanation tonometry, and dilated fundus examination were performed on each astronaut before and after their missions, and in-flight visual acuity testing was done on flight day 30, 90, and R-30 (30 d before return). They were also questioned regarding visual changes during flight. DISCUSSION: We documented stable vision in both PRK and LASIK astronauts during liftoff, entry into microgravity, 6 mo on the International Space Station, descent, and landing. Our results suggest that both PRK and LASIK are stable and well tolerated during long -duration spaceflight.

ImportanceUnderstanding potential predisposing factors associated with spaceflight-associated neuro-ocular syndrome (SANS) may influence its management.ObjectiveTo describe a severe case of SANS associated with 2 potentially predisposing factors.Design, Setting, and ParticipantsOcular testing of and blood collections from a female astronaut were completed preflight, inflight, and postflight in the setting of the International Space Station (ISS).ExposureWeightlessness throughout an approximately 6-month ISS mission. Mean carbon dioxide (CO2) partial pressure decreased from 2.6 to 1.3 mm Hg weeks before the astronaut’s flight day (FD) 154 optical coherence tomography (OCT) session. In response to SANS, 4 B-vitamin supplements (vitamin B6, 100 mg; L-methylfolate, 5 mg; vitamin B12, 1000 μg; and riboflavin, 400 mg) were deployed, unpacked on FD153, consumed daily through FD169, and then discontinued due to gastrointestinal discomfort.Main Outcomes and MeasuresRefraction, distance visual acuity (DVA), optic nerve, and macular assessment on OCT.ResultsCycloplegic refraction was −1.00 diopter in both eyes preflight and +0.50 − 0.25 × 015 in the right eye and +1.00 diopter in the left eye 3 days postflight. Uncorrected DVA was 20/30 OU preflight, 20/16 or better by FD90, and 20/15 OU 3 days postflight. Inflight peripapillary total retinal thickness (TRT) peaked between FD84 and FD126 (right eye, 401 μm preflight, 613 μm on FD84; left eye, 404 μm preflight, 636 μm on FD126), then decreased. Peripapillary choroidal folds, quantified by surface roughness, peaked at 12.7 μm in the right eye on FD154 and 15.0 μm in the left eye on FD126, then decreased. Mean choroidal thickness increased throughout the mission. Genetic analyses revealed 2 minor alleles for MTRR 66 and 2 major alleles for SHMT1 1420 (ie, 4 of 4 SANS risk alleles). One-week postflight, lumbar puncture opening pressure was normal, at 19.4 cm H2O.Conclusions and RelevanceTo the authors’ knowledge, no other report of SANS documented as large of a change in peripapillary TRT or hyperopic shift during a mission as in this astronaut, and this was only 1 of 4 astronauts to experience chorioretinal folds approaching the fovea. This case showed substantial inflight improvement greater than the sensitivity of the measure, possibly associated with B-vitamin supplementation and/or reduction in cabin CO2. However, as a single report, such improvement could be coincidental to these interventions, warranting further evaluation.

Spaceflight associated neuro-ocular syndrome (SANS) refers to a distinct constellation of ocular, neurological and neuroimaging findings observed in astronauts during and following long duration spaceflight. These ocular findings, to include optic disc oedema, posterior globe flattening, chorioretinal folds and hyperopic shifts, were first described by NASA in 2011. SANS is a potential risk to astronaut health and will likely require mitigation prior to planetary travel with prolonged exposures to microgravity. While the exact pathogenesis of SANS is not completely understood, several hypotheses have been proposed to explain this neuro-ocular phenomenon. In this paper, we briefly discuss the current hypotheses and contributing factors underlying SANS pathophysiology as well as analogues used to study SANS on Earth. We also review emerging potential countermeasures for SANS including lower body negative pressure, nutritional supplementation and translaminar pressure gradient modulation. Ongoing investigation within these fields will likely be instrumental in preparing and protecting astronaut vision for future spaceflight missions including deep space exploration.

ImportanceThe primary contributing factor for development of chorioretinal folds during spaceflight is unknown. Characterizing fold types that develop and tracking their progression may provide insight into the pathophysiology of spaceflight-associated neuro-ocular syndrome and elucidate the risk of fold progression for future exploration-class missions exceeding 12 months in duration.ObjectiveTo determine the incidence and presentation of chorioretinal folds in long-duration International Space Station crew members and objectively quantify the progression of choroidal folds during spaceflight.Design, Setting, and ParticipantsIn this retrospective cohort study, optical coherence tomography scans of the optic nerve head and macula of crew members completing long-duration spaceflight missions were obtained on Earth prior to spaceflight and during flight. A panel of experts examined the scans for the qualitative presence of chorioretinal folds. Peripapillary total retinal thickness was calculated to identify eyes with optic disc edema, and choroidal folds were quantified based on surface roughness within macular and peripapillary regions of interest.Interventions or ExposuresSpaceflight missions ranging 6 to 12 months.Main Outcomes and MeasuresIncidence of peripapillary wrinkles, retinal folds, and choroidal folds; peripapillary total retinal thickness; and Bruch membrane surface roughness.ResultsA total of 36 crew members were analyzed (mean [SD] age, 46 [6] years; 7 [19%] female). Chorioretinal folds were observed in 12 of 72 eyes (17%; 6 crew members). In eyes with early signs of disc edema, 10 of 42 (24%) had choroidal folds, 4 of 42 (10%) had inner retinal folds, and 2 of 42 (5%) had peripapillary wrinkles. Choroidal folds were observed in all eyes with retinal folds and peripapillary wrinkles. Macular choroidal folds developed in 7 of 12 eyes (4 of 6 crew members) with folds and progressed with mission duration; these folds extended into the fovea in 6 eyes. Circumpapillary choroidal folds developed predominantly superior, nasal, and inferior to the optic nerve head and increased in prevalence and severity with mission duration.Conclusions and RelevanceChoroidal folds were the most common fold type to develop during spaceflight; this differs from reports in idiopathic intracranial hypertension, suggesting differences in the mechanisms underlying fold formation. Quantitative measures demonstrate the development and progression of choroidal folds during weightlessness, and these metrics may help to assess the efficacy of spaceflight-associated neuro-ocular syndrome countermeasures.

Background: Long-duration spaceflight crewmembers are at risk for spaceflight-associated neuro-ocular syndrome (SANS). One of the earliest manifestations of SANS is optic disc edema (ODE), which could be missed using the subjective Frisén scale. The primary objective of this study is to determine the inter-rater and intrarater reliability of Frisén grade for SANS-induced ODE among a trained observer cohort. The secondary objective is to propose a standardized evaluation process for SANS-induced ODE across International Space Station Partner Agencies. Methods: Retrospective, double-blinded diagnostic study. Preflight and postflight fundus photographs were presented to subject matter experts who identified and graded ODE. Pairs of images were also compared side-by-side for disc ranking. Grader concordance was assessed for Frisén grading and disc ranking. Results: Expert graders identified Grade 1 ODE in 17.35% of images from 62 crewmembers (9 female, mean [SD] age, 47.81 [5.19] years). Grades 2 and 3 were identified less than 2% of the time. Concordance in Frisén grades among pairs of graders was 70.99%. Graders identified a difference in preflight and postflight fundus photographs 17.21% of the time when using disc ranking. Pairs of graders had complete concordance in disc ranking 79.79% of the time. Perfect intrarater agreement between Frisén grade and disc ranking occurred 77.7% of the time. Conclusions: These findings demonstrate intergrader and intragrader variability when using the Frisén scale to identify SANS-induced ODE, which is typically milder in presentation than terrestrial cases of idiopathic intracranial hypertension. It is possible to miss early ODE on fundoscopy alone, making it insufficient as a sole criterion for the diagnosis of SANS. A more sensitive and objective method of surveillance is necessary to monitor international crewmembers for ODE, perhaps using a multimodal approach that includes technology such as optical coherence tomography.

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Posterior globe flattening has been well-documented in astronauts both during and after long-duration space flight (LDSF) and has been observed as early as 10 days into a mission on the International Space Station. Globe flattening (GF) is thought to be caused by the disc centred anterior forces created by elevated volume and/or pressure within the optic nerve sheath (ONS). This might be the result of increased intracranial pressure, increased intraorbital ONS pressure from compartmentalisation or a combination of these mechanisms. We report posterior GF in three astronauts that has persisted for 7 years or more following their return from LDSFs suggesting that permanent scleral remodelling may have occurred.

Background: Spaceflight-associated neuro-ocular syndrome (SANS) was first described in 2011 and is associated with structural ocular changes found to occur in astronauts after long-duration missions. Despite multiple insufficient potential terrestrial models, an understanding of the etiology has yet to be described. Evidence Acquisition: A systematic review was conducted on literature published about the pathophysiology of cerebral edema. Databases searched include PubMed, Scopus, and the Texas Medical Center Online Library. This information was then applied to create theories on mechanisms on SANS etiology. Results: Cerebral edema occurs through 2 general mechanisms: redistribution of ions and water intracellularly and displacement of ions and water from the vascular compartment to the brain parenchyma. These processes occur through interconnected endocrine and inflammatory pathways and involve mediators such as cytokines, matrix metalloproteases, nitric oxide, and free radicals. The pathways ultimately lead to a violation of cellular membrane ionic gradients and blood-brain barrier degradation. By applying the principles of cerebral edema pathophysiology to the optic disc edema (ODE) see in SANS, several theories regarding its etiology can be formed. Venous stasis may lead to ODE through venous and capillary distension and leak, as well as relative hypoxia and insufficient ATP substrate delivery causing axoplasmic flow stasis and local oxidative stress. Conclusions: Using the pathophysiology of cerebral edema as a model, hypotheses can be inferred as to the etiology of ODE in SANS. Further studies are needed to determine the presence and contribution of local vascular stasis and resulting inflammation and oxidative stress to the pathophysiology of SANS.

INTRODUCTION: Spaceflight Associated Neuro-ocular Syndrome (SANS) results from long-duration spaceflight and presents with a constellation of signs (e.g., optic disc edema, choroidal folds, globe flattening, refractive error shifts, etc.). Optic nerve tortuosity (ONT) has been detected in approximately 47% of astronauts after long-duration spaceflight but has not yet been fully analyzed. This review examines terrestrial ONT in order to better understand how the condition is caused and measured.METHODS: References were identified by PubMed and ScienceDirect searches covering 1955 to October 2018 using the terms "optic nerve tortuosity," "optic nerve kinking," "optic disc torsion," "optic kinking," and "ocular torsion." Additional references were identified by searching relevant articles.RESULTS: ONT measurements have evolved and become more objective. One measure consists of meeting two criteria: 1) lack of optic nerve congruity in >1 coronal section; and 2) subarachnoid space dilation. This "criteria measure" is objective, sensitive, and specific for determining the presence of tortuosity. Another measure is the tortuosity index, which offers additional benefits by measuring the degree of ONT, including the potential to track changes over time. There are numerous terrestrial ONT causes, including intracranial hypertension, hydrocephalus, Chiari malformation, neurofibromatosis, glaucoma, and progeria, among others.DISCUSSION: To accurately measure ONT, it is crucial to adhere to objective, standardized techniques. The tortuosity index offers the potential to measure intraindividual change in ONT. Among the varied conditions associated with ONT, one commonality is pressure change. The impact of intracranial pressure on the vascular system and vice versa may offer insight into what is occurring in space.Scott RA, Tarver WJ, Brunstetter TJ, Urquieta E. Optic nerve tortuosity on Earth and in space. Aerosp Med Hum Perform. 2020; 91(2):91-97.

Prolonged microgravity exposure during long-duration spaceflight (LDSF) produces unusual physiologic and pathologic neuro-ophthalmic findings in astronauts. These microgravity associated findings collectively define the “Spaceflight Associated Neuro-ocular Syndrome” (SANS). We compare and contrast prior published work on SANS by the National Aeronautics and Space Administration’s (NASA) Space Medicine Operations Division with retrospective and prospective studies from other research groups. In this manuscript, we update and review the clinical manifestations of SANS including: unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and focal areas of ischemic retina (i.e., cotton wool spots). We also discuss the knowledge gaps for in-flight and terrestrial human research including potential countermeasures for future study. We recommend that NASA and its research partners continue to study SANS in preparation for future longer duration manned space missions.

NASA’s plans for space exploration include a return to the Moon to stay—boots back on the lunar surface with an orbital outpost. This station will be a launch point for voyages to destinations further away in our solar system, including journeys to the red planet Mars. To ensure success of these missions, health and performance risks associated with the unique hazards of spaceflight must be adequately controlled. These hazards—space radiation, altered gravity fields, isolation and confinement, closed environments, and distance from Earth—are linked with over 30 human health risks as documented by NASA’s Human Research Program. The programmatic goal is to develop the tools and technologies to adequately mitigate, control, or accept these risks. The risks ranked as “red” have the highest priority based on both the likelihood of occurrence and the severity of their impact on human health, performance in mission, and long-term quality of life. These include: (1) space radiation health effects of cancer, cardiovascular disease, and cognitive decrements (2) Spaceflight-Associated Neuro-ocular Syndrome (3) behavioral health and performance decrements, and (4) inadequate food and nutrition. Evaluation of the hazards and risks in terms of the space exposome—the total sum of spaceflight and lifetime exposures and how they relate to genetics and determine the whole-body outcome—will provide a comprehensive picture of risk profiles for individual astronauts. In this review, we provide a primer on these “red” risks for the research community. The aim is to inform the development of studies and projects with high potential for generating both new knowledge and technologies to assist with mitigating multisystem risks to crew health during exploratory missions.

IMPORTANCE Exposure to a weightless environment during spaceflight results in a chronic headward blood and tissue fluid shift compared with the upright posture on Earth, with unknown consequences to cerebral venous outflow. OBJECTIVES To assess internal jugular vein (IJV) flow and morphology during spaceflight and to investigate if lower body negative pressure is associated with reversing the headward fluid shift experienced during spaceflight. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study included 11 International Space Station crew members participating in long-duration spaceflight missions. Internal jugular vein measurements from before launch and approximately 40 days after landing were acquired in 3 positions: seated, supine, and 15 degrees head-down tilt. In-flight IJV measurements were acquired at approximately 50 days and 150 days into spaceflight during normal spaceflight conditions as well as during use of lower body negative pressure. Data were analyzed in June 2019. EXPOSURES Posture changes on Earth, spaceflight, and lower body negative pressure. MAIN OUTCOMES AND MEASURES Ultrasonographic assessments of IJV cross-sectional area, pressure, blood flow, and thrombus formation. RESULTS The 11 healthy crew members included in the study (mean [SD] age, 46.9 [6.3] years, 9 [82%] men) spent a mean (SD) of 210 (76) days in space. Mean IJV area increased from 9.8 (95% CI, -1.2 to 20.7) mm(2) in the preflight seated position to 70.3 (95% CI, 59.3-81.2) mm(2) during spaceflight (P < .001). Mean IJV pressure increased from the preflight seated position measurement of 5.1 (95% CI, 2.5-7.8) mm Hg to 21.1 (95% CI, 18.5-23.7) mm Hg during spaceflight (P < .001). Furthermore, stagnant or reverse flow in the IJV was observed in 6 crew members (55%) on approximate flight day 50. Notably, 1 crew member was found to have an occlusive IJV thrombus, and a potential partial IJV thrombus was identified in another crew member retrospectively. Lower body negative pressure was associated with improved blood flow in 10 of 17 sessions (59%) during spaceflight. CONCLUSIONS AND RELEVANCE This cohort study found stagnant and retrograde blood flow associated with spaceflight in the IJVs of astronauts and IJV thrombosis in at least 1 astronaut, a newly discovered risk associated with spaceflight. Lower body negative pressure may be a promising countermeasure to enhance venous blood flow in the upper body during spaceflight.

Individuals frequently seek medical care for musculoskeletal disorders of the shoulder and astronauts are no different. The purpose of this study was: 1) to determine the impact of age and sex as risk factors for orthopedic shoulder consultations and surgery in a cohort population; and 2) to determine if NASA astronauts are at a higher risk for consultations and surgery than a cohort population. The cohort (n = 347,540) was a group of working individuals that participated in a capitated insurance plan managed by their employers over a 10-year period. The astronaut cohort was comprised of NASA astronauts selected from 1959 through December 31, 2014 (n = 338). Both populations were limited to individuals between 25 and 64 years. Incidence rates indicate that age and sex were risk factors for consultation and surgery. As age increased, consultations increased significantly for both sexes in a stair-step manner. Males consistently had a higher rate than females in all age categories (all p 0.001) except for 55-64 year-olds (p = 0.228). Survival analysis confirmed that age (p < 0.001) was a significant risk factor and that male astronauts had a higher rate of consultations (p < 0.001) but not surgery (p = 0.938) as compared to the male cohort. The consultation rates were not significantly different in females when accounting for follow-up time (p = 0.14). Cohort data show that both age and sex were risk factors for consultation and surgery. Additionally, male astronauts were referred to orthopedists more often than the cohort population, but surgery rates did not differ between groups.

Interesting novel and somewhat perplexing physiologic and pathologic neuro-ocular findings have been documented in astronauts during and after long duration space flight (LDSF). These findings collectively have been termed the “space flight-associated neuro-ocular syndrome” (SANS). The National Aeronautics and Space Administration (NASA) in the United States has meticulously and prospectively documented the clinical, ultrasound, optical coherence tomography imaging, and radiographic findings of SANS including unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts (i.e., cotton wool spots). NASA and collaborating researchers continue to study SANS in preparation for future manned missions to space, including continued trips to the ISS, a return to the moon, or perhaps new voyages to the asteroid belt, or the planet, Mars.

While astronauts are returning from long duration spaceflight with multiple ocular signs that mimic those seen in terrestrial patients with elevated intracranial pressure (ICP), evidence has yet to prove a clinically significant increase in ICP during space.1 Preliminary research evidence may even suggest that ICP decreases in microgravity. Idiopathic intracranial hypertension (IIH) has long been considered the ideal terrestrial analogue to Spaceflight Associated Neuro-ocular Syndrome (SANS).1 However, there are several critical features of SANS that do not complement any reported case of IIH on Earth. These findings mandate a closer look at the accuracy of IIH as a terrestrial SANS analog.

Vision changes identified in long duration spaceflight astronauts has led Space Medicine at NASA to adopt a more comprehensive clinical monitoring protocol. Optical Coherence Tomography (OCT) was recently implemented at NASA, including on board the International Space Station in 2013. NASA is collaborating with Heidelberg Engineering to increase the fidelity of the current OCT data set by integrating the traditional circumpapillary OCT image with radial and horizontal block images at the optic nerve head. The retinal nerve fiber layer was segmented by two experienced individuals. Intra-rater (N=4 subjects and 70 images) and inter-rater (N=4 subjects and 221 images) agreement was performed. The results of this analysis and the potential benefits will be presented.