Spaceflight-associated Neuro-ocular Syndrome Research Articles

Women in space: A review of known physiological adaptations and health perspectives.

Exposure to the spaceflight environment causes adaptations in most human physiological systems, many of which are thought to affect women differently from men. Since only 11.5% of astronauts worldwide have been female, these issues are largely understudied. The physiological nuances affecting the female body in the spaceflight environment remain inadequately defined since the last thorough published review on the subject. A PubMed literature search yielded over 2200 publications. Using NASA's 2014 review series 'The effects of sex and gender on adaptation to space' as a benchmark, we identified substantive advancements and persistent knowledge gaps in need of further study from the nearly 600 related articles that have been published since the initial review. This review highlights the most critical issues to mitigate medical risk and promote the success of missions to the Moon and Mars. Salient sex-linked differences observed terrestrially should be studied during upcoming missions, including increased levels of inflammatory markers, coagulation factors and leptin levels following sleep deprivation; correlation between body mass and the severity of spaceflight-associated neuro-ocular syndrome; increased incidence of orthostatic intolerance; increased severity of muscle atrophy and bone loss; differences in the incidence of urinary tract infections; and susceptibility to specific cancers after exposure to ionizing radiation. To optimize health and well-being among all astronauts, it is imperative to prioritize research that considers the physiological nuances of the female body. A more robust understanding of female physiology in the spaceflight environment will support crew readiness for Artemis missions and beyond.

Artificial gravity: an effective countermeasure for microgravity-induced headward fluid shift?

Long-duration spaceflight is associated with pathophysiological changes in the intracranial compartment hypothetically linked to microgravity-induced headward fluid shift. This study aimed to determine whether daily artificial gravity (AG) sessions can mitigate these effects, supporting its application as a countermeasure to spaceflight. Twenty-four healthy adult volunteers (16 men) were exposed to 60 days of 6° head-down tilt bed rest (HDTBR) as a ground-based analog of chronic headward fluid shift. Subjects were divided equally into three groups: no AG (control), daily 30-min intermittent AG (iAG), and daily 30-min continuous (cAG). Internal carotid artery (ICA) stroke volume (ICASV), ICA resistive index (ICARI), ICA flow rate (ICAFR), aqueductal cerebral spinal fluid flow velocity (CSFV), and intracranial volumetrics were quantified at 3 T. MRI was performed at baseline, 14 and 52 days into HDTBR, and 3 days after HDTBR (recovery). A mixed model approach was used with intervention and time as the fixed effect factors and the subject as the random effect factor. Compared with baseline, HDTBR was characterized by expansion of lateral ventricular, white matter, gray matter, and brain + total intracranial cerebral spinal fluid volumes, increased CSFv, decreased ICASV, and decreased ICAFR by 52 days into HBTBR (All Ps < 0.05). ICARI was only increased 14 days into HDTBR (P < 0.05). Neither iAG nor cAG significantly affected measurements compared with HDTBR alone, indicating that 30 min of daily exposure was insufficient to mitigate the intracranial effects of headward fluid shift. Greater AG session exposure time, gravitational force, or both are suggested for future countermeasure research.NEW & NOTEWORTHY Brief exposure to continuous or intermittent artificial gravity via short-arm centrifugation was insufficient in mitigating the intracranial pathophysiological effects of the headward fluid shift simulated during head-down tilt bed rest (HDTBR). Our results suggest that greater centrifugation session duration, gravitational force, or both may be required to prevent the development of spaceflight-associated neuro-ocular syndrome and should be considered in future ground-based countermeasure studies.

Differential Functional Changes in Visual Performance during Acute Exposure to Microgravity Analogue and Their Potential Links with Spaceflight-Associated Neuro-Ocular Syndrome.

Spaceflight-Associated Neuro-Ocular Syndrome (SANS) is a complex pathology threatening the health of astronauts, with incompletely understood causes and no current specific functional diagnostic or screening test. We investigated the use of the differential performance of the visual system (central vs. perimacular visual function) as a candidate marker of SANS-related pathology in a ground-based microgravity analogue. We used a simple reaction time (SRT) task to visual stimuli, presented in the central and perimacular field of view, as a measure of the overall performance of the visual function, during acute settings (first 10 min) of vertical, bed rest (BR), -6°, and -15° head-down tilt (HDT) presentations in healthy participants (n = 8). We built dose-response models linking the gravitational component to SRT distribution parameters in the central vs. perimacular areas. Acute exposure to microgravity induces detectable changes between SRT distributions in the perimacular vs. central retina (increased mean, standard deviation, and tau component of the ex-Gaussian function) in HDT compared with vertical presentation. Functional testing of the perimacular retina might be beneficial for the earlier detection of SANS-related ailments in addition to regular testing of the central vision. Future diagnostic tests should consider the investigation of the extra-macular areas, particularly towards the optic disc.

Severe Spaceflight-Associated Neuro-Ocular Syndrome in an Astronaut With 2 Predisposing Factors

Understanding potential predisposing factors associated with spaceflight-associated neuro-ocular syndrome (SANS) may influence its management. To describe a severe case of SANS associated with 2 potentially predisposing factors. Ocular testing of and blood collections from a female astronaut were completed preflight, inflight, and postflight in the setting of the International Space Station (ISS). Weightlessness 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. Refraction, distance visual acuity (DVA), optic nerve, and macular assessment on OCT. Cycloplegic 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. To 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.

Self-Generated Lower Body Negative Pressure Exercise: A Low Power Countermeasure for Acute Space Missions.

Microgravity in spaceflight produces headward fluid shifts which probably contribute to Spaceflight-Associated Neuro-Ocular Syndrome (SANS). Developing new methods to mitigate these shifts is crucial for preventing SANS. One possible strategy is the use of self-generated lower body negative pressure (LBNP). This study evaluates biological or physiological effects induced by bed rest to simulate adaptations to microgravity. Participants were tested during powered LBNP and dynamic self-generated (SELF) LBNP at 25 mmHg for 15 min. The results were compared to the physiologic responses observed in seated upright and supine positions without LBNP, which served as controls for normal gravitational effects on fluid dynamics. Eleven participants' (five male, six female) heart rates, blood pressures, and cross-sectional areas (CSA) of left and right internal jugular veins (IJV) were monitored. Self-generated LBNP, which requires mild to moderate physical activity, significantly elevated heart rate and blood pressure (p < 0.01). Self-generated LBNP also significantly reduced right IJV CSA compared to supine position (p = 0.005), though changes on the left side were not significant (p = 0.365). While the effects of SELF and traditional LBNP on IJV CSA were largely similar, traditional LBNP significantly reduced IJV CSA on both sides. Given its low mass, volume, and power requirements, SELF LBNP is a promising countermeasure against SANS. Results from this study warrant longer-term studies of SELF LBNP under simulated spaceflight conditions.

Daily use of veno-constrictive thigh cuffs during 30 days of strict 6° head-down tilt bedrest to reverse the headward fluid shift

Introduction: Chronic exposure to weightlessness induces a persistent headward fluid shift, which may contribute to the development of Spaceflight Associated Neuro-ocular Syndrome (SANS). Strict 6° head-down tilt bedrest (HDTBR) is a spaceflight analog that induces a headward fluid shift and development of SANS findings, enabling the evaluation of potential countermeasures. Lower body exercise can induce a sustained post-exercise hyperemia thereby shifting blood away from the central circulation. In addition, veno-constrictive thigh cuffs (VTC) can sequester blood volume in the legs. The purpose of this study was to determine whether 6 hours of daily VTC use following cycling exercise (Ex+VTC) could reverse the headward fluid shift during 30 days of strict 6° HDTBR. We hypothesized that Ex+VTC would sequester fluid in the legs leading to increased thigh circumference and reduced stroke volume (SV), cardiac output (CO), internal jugular vein (IJV) cross-sectional area (CSA) and pressure, and intraocular pressure (IOP). Methods: Participants were randomly assigned to a Control (n=12, 6 female) or Ex+VTC (n=12, 4 female) group and completed baseline data collection (BDC) in the seated and supine posture followed by 30 days of strict 6° HDTBR. The Ex+VTC group completed a maximal exercise test on a cycle ergometer in 6° HDT posture during BDC to establish work rates during HDTBR. The Ex+VTC group performed 10 minutes of light cycle exercise, cycled for 45 minutes at 45% of their max wattage, and then donned VTC to ~50 mmHg for 6 hours on 6 of 7 days per week during HDTBR. Data were collected before exercise and 30 minutes and 6 hours after exercise and donning VTCs on days 3, 17, and 29 of HDTBR. Controls were studied at similar time points. Days were nested within the models. Mixed models were used to determine differences between groups in the change in thigh circumference measured using a flexible tape measure, bilateral IOP measured using tonometry, CO measured using the inert gas rebreathe technique (Innocor), and ultrasound of bilateral IJV CSA and pressure from before to 30 min and 6 hours after use of the countermeasure. Left and right IJV and IOP data were nested within each participant. Results: The Ex+VTC group completed all exercise sessions followed by 6 hours of VTC use. Compared to Control, thigh circumference was greater after 30 minutes (+1.3 vs. -0.2 cm, p&lt;0.001) and 6 hours of VTC use (+2.5 cm vs. -0.1 cm in controls, p&lt;0.001). SV (-38 vs. 2 ml, p&lt;0.001) and CO (-1.5 vs. 0.3 L/min, p&lt;0.001) were reduced at 30 minutes and 6 hours of VTC use (SV: -30 vs. 5 ml, p&lt;0.001; CO: -1.1 vs. 0.6 L/min, p&lt;0.001) compared to Control. IJV CSA and pressure were reduced at 30 minutes (CSA, p&lt;0.001; pressure, p=0.001) and 6 hours of VTC use (CSA, p&lt;0.001; pressure, p=0.007). IOP was not different compared to Control. Conclusions:Use of VTC for 6 hours after 45 minutes of exercise successfully sequestered fluid in the legs, leading to a reduction in central blood volume, IJV CSA, and IJV pressure. Thus, an Ex+VTC countermeasure resulted in a partial fluid shift reversal. This research was supported by the NASA Human Research Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Modeling the impact of thoracic pressure on intracranial pressure

A potential contribution to the progression of Spaceflight Associated Neuro-ocular Syndrome is the thoracic-to-spinal dural sac transmural pressure relationship. In this study, we utilize a lumped-parameter computational model of human cerebrospinal fluid (CSF) systems to investigate mechanisms of CSF redistribution. We present two analyses to illustrate potential mechanisms for CSF pressure alterations similar to those observed in microgravity conditions. Our numerical evidence suggests that the compliant relationship between thoracic and CSF compartments is insufficient to solely explain the observed decrease in CSF pressure with respect to the supine position. Our analyses suggest that the interaction between thoracic pressure and the cardiovascular system, particularly the central veins, has greater influence on CSF pressure. These results indicate that future studies should focus on the holistic system, with the impact of cardiovascular changes to the CSF pressure emphasized over the sequestration of fluid in the spine.

SANS-CNN: An automated machine learning technique for spaceflight associated neuro-ocular syndrome with astronaut imaging data

Spaceflight associated neuro-ocular syndrome (SANS) is one of the largest physiologic barriers to spaceflight and requires evaluation and mitigation for future planetary missions. As the spaceflight environment is a clinically limited environment, the purpose of this research is to provide automated, early detection and prognosis of SANS with a machine learning model trained and validated on astronaut SANS optical coherence tomography (OCT) images. In this study, we present a lightweight convolutional neural network (CNN) incorporating an EfficientNet encoder for detecting SANS from OCT images titled “SANS-CNN.” We used 6303 OCT B-scan images for training/validation (80%/20% split) and 945 for testing with a combination of terrestrial images and astronaut SANS images for both testing and validation. SANS-CNN was validated with SANS images labeled by NASA to evaluate accuracy, specificity, and sensitivity. To evaluate real-world outcomes, two state-of-the-art pre-trained architectures were also employed on this dataset. We use GRAD-CAM to visualize activation maps of intermediate layers to test the interpretability of SANS-CNN’s prediction. SANS-CNN achieved 84.2% accuracy on the test set with an 85.6% specificity, 82.8% sensitivity, and 84.1% F1-score. Moreover, SANS-CNN outperforms two other state-of-the-art pre-trained architectures, ResNet50-v2 and MobileNet-v2, in accuracy by 21.4% and 13.1%, respectively. We also apply two class-activation map techniques to visualize critical SANS features perceived by the model. SANS-CNN represents a CNN model trained and validated with real astronaut OCT images, enabling fast and efficient prediction of SANS-like conditions for spaceflight missions beyond Earth’s orbit in which clinical and computational resources are extremely limited.

Spaceflight-associated neuro-ocular syndrome: potential etiologies and connections to the glymphatic system.

The etiology of spaceflight-associated neuro-ocular syndrome (SANS) is a developing field of research, with many current hypotheses receiving varying degrees of support. This syndrome affects ∼70% of astronauts both during and after long-duration space missions, resulting in impaired near vision and visual scotomas (blind spots). In this article, three prominent risk factors for SANS including zero gravity conditions, extraterrestrial hypercapnic environments, and individual genetic predisposition are described. These risk factors are then compared and their pathophysiological pathways are divided into five current hypotheses for the development of SANS. Finally, glymphatic system impairment is explored as a potential mutual end point for these pathways in the development of SANS.

Ultrasound Biomicroscopy as a Novel, Potential Modality to Evaluate Anterior Segment Ophthalmic Structures during Spaceflight: An Analysis of Current Technology.

Ocular health is currently a major concern for astronauts on current and future long-duration spaceflight missions. Spaceflight-associated neuro-ocular syndrome (SANS) is a collection of ophthalmic and neurologic findings that is one potential physiologic barrier to interplanetary spaceflight. Since its initial report in 2011, our understanding of SANS has advanced considerably, with a primary focus on posterior ocular imaging including fundus photography and optical coherence tomography. However, there may be changes to the anterior segment that have not been identified. Additional concerns to ocular health in space include corneal damage and radiation-induced cataract formation. Given these concerns, precision anterior segment imaging of the eye would be a valuable addition to future long-duration spaceflights. The purpose of this paper is to review ultrasound biomicroscopy (UBM) and its potential as a noninvasive, efficient imaging modality for spaceflight. The analysis of UBM for spaceflight is not well defined in the literature, and such technology may help to provide further insights into the overall anatomical changes in the eye in microgravity.

Dynamic changes in perivascular space morphology predict signs of spaceflight-associated neuro-ocular syndrome in bed rest

During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Linking cerebral hemodynamics and ocular microgravity-induced alterations through an in silico-in vivo head-down tilt framework

Head-down tilt (HDT) has been widely proposed as a terrestrial analog of microgravity and used also to investigate the occurrence of spaceflight-associated neuro-ocular syndrome (SANS), which is currently considered one of the major health risks for human spaceflight. We propose here an in vivo validated numerical framework to simulate the acute ocular-cerebrovascular response to 6° HDT, to explore the etiology and pathophysiology of SANS. The model links cerebral and ocular posture-induced hemodynamics, simulating the response of the main cerebrovascular mechanisms, as well as the relationship between intracranial and intraocular pressure to HDT. Our results from short-term (10 min) 6° HDT show increased hemodynamic pulsatility in the proximal-to-distal/capillary-venous cerebral direction, a marked decrease (-43%) in ocular translaminar pressure, and an increase (+31%) in ocular perfusion pressure, suggesting a plausible explanation of the underlying mechanisms at the onset of ocular globe deformation and edema formation over longer time scales.

Development of optic disc edema during 30 days of hypercapnic head-down tilt bed rest is associated with short sleep duration and blunted temperature amplitude.

Sleep and circadian temperature disturbances occur with spaceflight and may, in part, result from the chronically elevated carbon dioxide (CO2) levels on the international space station. Impaired sleep may contribute to decreased glymphatic clearance and, when combined with the chronic headward fluid shift during actual spaceflight or the spaceflight analog head-down tilt bed rest (HDTBR), may contribute to the development of optic disc edema. We determined if strict HDTBR combined with mildly elevated CO2 levels influenced sleep and core temperature and was associated with the development of optic disc edema. Healthy participants (5 females) aged 25-50 yr, underwent 30 days of strict 6° HDTBR with ambient Pco2 = 4 mmHg. Measures of sleep, 24-h core temperature, overnight transcutaneous CO2, and Frisén grade edema were made pre-HDTBR, on HDTBR days 4, 17, 28, and post-HDTBR days 4 and 10. During all HDTBR time points, sleep, core temperature, and overnight transcutaneous CO2 were not different than the pre-HDTBR measurements. However, independent of the HDTBR intervention, the odds ratios {mean [95% confidence interval (CI)]} for developing Frisén grade optic disc edema were statistically significant for each hour below the mean total sleep time (2.2 [1.1-4.4]) and stage 2 nonrapid eye movement (NREM) sleep (4.8 [1.3-18.6]), and above the mean for wake after sleep onset (3.6 [1.2-10.6]) and for each 0.1°C decrease in core temperature amplitude below the mean (4.0 [1.4-11.7]). These data suggest that optic disc edema occurring during HDTBR was more likely to occur in those with short sleep duration and/or blunted temperature amplitude.NEW & NOTEWORTHY We determined that sleep and 24-h core body temperature were unaltered by 30 days exposure to the spaceflight analog strict 6° head-down tilt bed rest (HDTBR) in a 0.5% CO2 environment. However, shorter sleep duration, greater wake after sleep onset, and lower core temperature amplitude present throughout the study were associated with the development of optic disc edema, a key finding of spaceflight-associated neuro-ocular syndrome.

FA4SANS-GAN: A Novel Machine Learning Generative Adversarial Network to Further Understand Ophthalmic Changes in Spaceflight Associated Neuro-Ocular Syndrome (SANS)

PurposeTo provide automated system for synthesizing fluorescein angiography (FA) images from color fundus (CF) photographs for averting risks associated with fluorescein dye and extend its future application to Space-associated neuro-ocular syndrome (SANS) detection in spaceflight where resources are limited. DesignDevelopment and validation of a novel conditional generative adversarial network (GAN) trained on limited amount of fluorescein angiography and color fundus images with diabetic retinopathy and control cases. ParticipantsColor fundus and fluorescein angiography paired images for unique patients were collected from a publicly available study. MethodsFA4SANS-GAN was trained to generate fluorescein angiography images from color fundus photographs using two multi-scale generators coupled with two patch-GAN discriminators. 850 CF and FA images were utilized for training by augmenting images from 17 unique patients. The model was evaluated on 56 fluorescein images collected from 14 unique patients. In addition, it was compared with three other GAN architectures trained on the same dataset. Furthermore, we test the robustness of the models against acquisition noise and retaining structural information when introduced to artificially created biological markers. Main Outcome MeasureFor GAN synthesis metric Fréchet Inception Distance (FID) and Kernel Inception Distance (KID). Also, two one-sided tests (TOST) based on Welch's t-test for measuring statistical significance. ResultsOn test FA images, mean FID for FA4SANS-GAN was 39.8 (SD 9.9), which is better than GANgio model’s mean of 43.2 (SD 13.7), Pix2PixHD’s mean of 57.3 (SD 11.5) and Pix2Pix’s mean of 67.5 (SD 11.7). Similarly for KID, FA4SANS-GAN achieved mean of 0.00278 (SD 0.00167) which is better than other three model’s mean KID of 0.00303 (SD 0.00216), 0.00609 (SD 0.00238), 0.00784 (SD 0.00218). For TOST measurement, FA4SANS-GAN has proven to be statistically significant vs. GANgio (p = 0.006); vs Pix2PixHD (p < 0.00001); and vs. Pix2Pix (p < 0.00001). ConclusionOur study has shown FA4SANS-GAN to be statistically significant for two GAN synthesis metrics. Moreover, it is robust against acquisition noise, and can retain clear biological markers compared to the other three GAN architectures. This deployment of this model can be crucial in International Space Station (ISS) for detecting Spaceflight-associated neuro-ocular syndrome (SANS).

Navigating the Unknown: A Comprehensive Review of Spaceflight-Associated Neuro-Ocular Syndrome.

Spaceflight-associated neuro-ocular syndrome (SANS) is a complex and multifaceted condition that affects astronauts during and after their missions in space. This comprehensive review delves into the various aspects of SANS, providing a thorough understanding of its definition, historical context, clinical presentation, epidemiology, diagnostic techniques, preventive measures, and management strategies. Various ocular and neurological symptoms, including visual impairment, optic disc edema, choroidal folds, retinal changes, and increased intracranial pressure, characterize SANS. While microgravity is a primary driver of SANS, other factors like radiation exposure, genetic predisposition, and environmental conditions within spacecraft contribute to its development. The duration of space missions is a significant factor, with longer missions associated with a higher incidence of SANS. This review explores the diagnostic criteria and variability in SANS presentation, shedding light on early detection and management challenges. The epidemiology section provides insights into the occurrence frequency, affected astronauts' demographics, and differences between long-term and short-term missions. Diagnostic tools, including ophthalmological assessments and imaging techniques, are crucial in monitoring astronaut health during missions. Preventive measures are vital in mitigating the impact of SANS. Current strategies, ongoing research in prevention methods, lifestyle and behavioral factors, and the potential role of artificial gravity are discussed in detail. Additionally, the review delves into interventions, potential pharmacological treatments, rehabilitation, and long-term management considerations for astronauts with SANS. The conclusion underscores the importance of continued research in SANS, addressing ongoing challenges, and highlighting unanswered questions. With the expansion of human space exploration, understanding and managing SANS is imperative to ensure the health and well-being of astronauts during long-duration missions. This review is a valuable resource for researchers, healthcare professionals, and space agencies striving to enhance our knowledge and address the complexities of SANS.

Spaceflight associated neuro-ocular syndrome: connections with terrestrial eye and brain disorders.

Spaceflight Associated Neuro-ocular Syndrome (SANS) is a series of findings found in astronauts who have experienced long-duration spaceflight. It is characterized by neuro-ocular changes that may irreversibly alter vision and increase the risk for the development of terrestrial eye and brain disorders. Theories regarding its etiology and countermeasures to combat the findings seen continue to evolve. There is currently no direct treatment for SANS. Traditional Chinese Medicine (TCM) modalities have been used to treat eye and brain disorders on Earth that are pathogenically similar to SANS, therefore, TCM may be able to target corresponding pathology in astronauts, prevent and mitigate SANS findings, and decrease the risk for future development of disorders. This paper intends to discuss pathological similarities between SANS and terrestrial eye and brain disorders and how TCM has been used to treat those disorders.

State of the Retina and Optic Nerve in 21-Day Head-Down Tilt Bed Rest

Studies in conditions of head-down tilt bed rest are widely used experiments which imitate redistribution of body fluids similar to the redistribution of fluid media in microgravity. To study the mechanism of development of spaceflight-associated neuro-ocular syndrome (SANS) in head-down tilt bed rest studies scientists have evaluated, among other things, participants’ visual system parameters. The main symptom of SANS is an edema of an optic disc and a retina. To date, the results describing the influence of head-down tilt bed rest on the visual system are ambiguous, which determines the relevance of further research. The aim of the study is to analyze retinal morphometry in the optic disc area and macular area in participants before and after 21-day head-down tilt bed rest. The study was performed using an optical coherence tomography with angiography function (Optovue RTVue XR Avanti System) before and after 21-days of head-down tilt bed rest. In 4 participants (8 eyes) (men, mean age ± standard deviation: 29.3 ± 3.9 years) the macular zone and optic disc area were evaluated according to standard scanning modes. To analyze the values obtained, we used mean tendency scores, mean comparison criteria, and graphical analysis. The results of the retinal thickness in the optic disc zone were consistent with those of other researchers, indicating a possible increase in retinal thickness, but our results did not reach the level of statistical significance. A statistically significant thickening of the retina in the macular zone was shown for the first time, but the increase is significantly less in amplitude than the thickening of the nerve fiber layer in the optic disc zone. Analysis of vascular density under head-down tilt bed rest conditions was performed for the first time both for the optic disc zone and the macula zone, but additional studies are required to obtain steady conclusions. For the first time, an increase in retinal thickness in the macula zone in participants of head-down tilt bed rest experiments was shown; for the optic disc zone, data consistent with the results of other researchers were obtained. For the first time, angiographic data were obtained for the macula and optic disk areas, but the obtained differences in vascular density did not reach the level of statistical significance.

Optic disc edema during strict 6° head-down tilt bed rest is related to one-carbon metabolism pathway genetics and optic cup volume.

Some astronauts on International Space Station missions experience neuroophthalmological pathologies as part of spaceflight associated neuro-ocular syndrome (SANS). Strict head-down tilt bed rest (HDTBR) is a spaceflight analog that replicates SANS findings and those who had 3-4 risk alleles (G and C alleles from the methionine synthase reductase [MTRR] A66G and serine hydroxymethyltransferase [SHMT1] C1420T, respectively) as compared to 1-2 risk alleles, had a greater increase in total retinal thickness (TRT). The objective of this study was to identify factors that contribute to the individual variability of the development of SANS in a 60d HDTBR at the German Aerospace Center's:envihab facility, Cologne Germany. 22 of 24 subjects who participated in the HDTBR study provided blood samples for genetic analysis. Total retinal thickness and optic cup volume were measured before and after bed rest. Subjects with 3-4 versus 0-2 risk alleles had greater ΔTRT during and after bed rest, and the model improved with the addition of baseline optic cup volume. This bed rest study confirms that variants of MTRR and SHMT1 are associated with ocular pathologies. Subjects with more risk alleles had the greatest HDTBR-induced ΔTRT, reaffirming that genetics predispose some individuals to developing SANS. Preflight optic cup volume and genetics better predict ΔTRT than either one alone. Whether nutritional supplements can override the genetic influences on biochemistry, physiology, and pathophysiology remains to be tested. These findings have significant implications for both aerospace and terrestrial medicine.

Ocular rigidity and choroidal thickness changes in response to microgravity: A case study

PurposeTo evaluate ocular rigidity and choroidal thickness changes in response to microgravity and the Valsalva maneuver in a private astronaut. MethodsOphthalmological examination and Optical Coherence Tomography were performed before, during, and after space flight. Choroidal thickness was measured at all time points at rest and during the Valsalva maneuver. Ocular rigidity was obtained before and after flight using a non-invasive method enhanced with deep learning-based choroid segmentation. ResultsOcular rigidity decreased after space flight compared to baseline. There was an increase in average choroidal thickness during the Valsalva maneuver compared to the resting condition before, during, and after space flight, and such increase was greater when the Valsalva maneuver was performed during space flight. Conclusions and importanceThe data indicates biomechanical changes to ocular tissues because of space flight and greater choroidal thickness increase. The findings could lead to a better understanding of space flight-associated neuro-ocular syndrome and may have repercussions for short duration missions in a nascent industry.

Intraocular Pressure during Spaceflight and Risk of Glaucomatous Damage in Prolonged Microgravity

Microgravity introduces diverse pathological and various physiological changes to the human body, including intraocular pressure. Astronauts may develop a constellation of symptoms and signs including optic disc edema, choroidal folds, and a hyperopic shift from the flattening of the globe. These ocular findings have been collectively termed spaceflight-associated neuro-ocular syndrome (SANS). SANS is a condition that is unique to long-duration spaceflight. The precise pathogenesis of SANS remains ill-defined, but several hypotheses have been proposed that may be influenced by intraocular pressure. Countermeasures for SANS research also include techniques that impact intraocular pressure. In this article, we discuss intraocular pressure during spaceflight, the translaminar pressure gradient, SANS and potential SANS countermeasures, and the potential for glaucomatous damage during spaceflight.