Spaceflight-associated Neuro-ocular Syndrome Research Articles

Change in Eye Hydrodynamics as a Pathogenesis Factor of Space-Flight Associated Neuro-Ocular Syndrome (SANS)

Change in Eye Hydrodynamics as a Pathogenesis Factor of Space-Flight Associated Neuro-Ocular Syndrome (SANS)

MRI-based quantification of posterior ocular globe flattening during 60 days of strict 6° head-down tilt bed rest with and without daily centrifugation.

Spaceflight associated neuro-ocular syndrome (SANS) is associated with acquired optic disc edema, hyperopia, and posterior globe flattening in some astronauts during long-duration spaceflight possibly due to the headward fluid redistribution in microgravity. The goal of this study was to assess whether strict head-down tilt (HDT) bed rest as a spaceflight analog would produce globe flattening and whether centrifugation could prevent these changes. Twenty-four healthy subjects separated into three groups underwent 60 days of strict 6° HDT bed rest: one control group with no countermeasure (n = 8) and two countermeasure groups exposed to 30 min daily of short-arm centrifugation as a means of artificial gravity (AG), either intermittent (iAG, n = 8) or continuous (cAG, n = 8). Magnetic resonance images (MRI) were collected at baseline, HDT-day 14, HDT-day 52, and 3 days after bed rest. An automated method was applied to quantify posterior globe volume displacement compared with baseline scans. On average, subjects showed an increasing degree of globe volume displacement with bed rest duration (means ± SE: 1.41 ± 1.01 mm3 on HDT14 and 4.04 ± 1.19 mm3 on HDT52) that persisted post-bed rest (5.51 ± 1.26 mm3). Application of 30 min daily AG did not have a significant impact on globe volume displacement (P = 0.42 for cAG and P = 0.93 for iAG compared with control). These results indicate that strict 6° HDT bed rest produced displacement of the posterior globe with a trend of increasing displacement with longer duration that was not prevented by daily 30 min exposure to AG.NEW & NOTEWORTHY Head-down tilt (HDT) bed rest is commonly used as a spaceflight analog for investigating spaceflight associated neuro-ocular syndrome (SANS). Posterior ocular globe flattening has been identified in astronauts with SANS but until now has not been investigated during HDT bed rest. In this study, posterior ocular globe volume displacement was quantified before, during, and after HDT bed rest and countermeasures were tested for their potential to reduce the degree of globe flattening.

The ex vivo human translaminar autonomous system to study spaceflight associated neuro-ocular syndrome pathogenesis

Spaceflight-Associated Neuro-ocular Syndrome (SANS) is a significant unexplained adverse reaction to long-duration spaceflight. We employ an ex vivo translaminar autonomous system (TAS) to recreate a human ocular ground-based spaceflight analogue model to study SANS pathogenesis. To recapitulate the human SANS conditions, human ocular posterior segments are cultured in the TAS model for 14 days. Translaminar pressure differentials are generated by simulating various flow rates within intracranial pressure (ICP) and intraocular (IOP) chambers to maintain hydrostatic pressures of ICP: IOP (12:16, 15:16, 12:21, 21:16 mmHg). In addition, optic nerves are mechanically kinked by 6- and 10-degree tilt inserts for the ICP: IOP;15:16 mmHg pressure paradigm. The TAS model successfully maintains various pressure differentials for all experimental groups over 14 days. Post culture, we determine inflammatory and extracellular component expression changes within posterior segments. To further characterize the SANS pathogenesis, axonal transport capacity, optic nerve degeneration and retinal functional are measured. Identifiable pathogenic alterations are observed in posterior segments by morphologic, apoptotic, and inflammatory changes including transport and functional deficits under various simulated SANS conditions. Here we report our TAS model provides a unique preclinical application system to mimic SANS pathology and a viable therapeutic testing device for countermeasures.

Identification of Factors Associated With the Development of Optic Disc Edema During Spaceflight

Approximately 70% of crew members who complete long-duration missions to the International Space Station develop signs of optic disc edema, a hallmark finding of spaceflight-associated neuro-ocular syndrome. The onset and magnitude of edema differ across individuals, and the reason for this variability remains unknown. Identifying risk factors for spaceflight-induced disc edema is important because this condition may become more severe during extended-duration missions to the moon and Mars and could be associated with irreversible vision loss. To assess whether preflight indicators of crowded optic nerve head morphology, other ocular measures (such as choroid thickness and axial length), body weight, body mass index, sex, age, and previous flight experience are associated with optic disc edema development. This cohort study analyzed ocular, body weight, and demographic data collected from 31 US and international crew members before, during, and after spaceflight at the NASA Johnson Space Center and International Space Station. Ocular factors assessed included preflight and in-flight peripapillary total retinal thickness, minimum rim width, optic cup volume, mean cup depth, mean cup width, cup-disc ratio, Bruch membrane opening area, retinal nerve fiber layer thickness, choroid thickness, axial length, and refractive error. In addition, body weight, body mass index, sex, age, and previous spaceflight experience were assessed for associations with optic disc edema development. The data were analyzed from August 2021 to June 2022. Approximately 6 to 12 months of spaceflight. In-flight increases in peripapillary total retinal thickness. Linear mixed models were used to assess for associations between a wide range of risk factors and in-flight increases in peripapillary total retinal thickness, which is a sensitive objective measure for detecting optic disc edema. This study included 31 International Space Station crew members with a mean (SD) age of 46.9 (6.0) years (25 men [80.6%]). During spaceflight, mean (SE) peripapillary total retinal thickness increased from 392.0 (5.8) μm to 430.2 (9.6) μm (P < .001), and greater individual changes were associated with smaller preflight cup volume (slope [SE], -62.8 [18.9]; P = .002), shallower preflight cup depth (slope [SE], -0.11 [0.03]; P < .001), and narrower preflight cup width (slope [SE], -0.03 [0.01]; P = .03). No associations were observed between changes in peripapillary total retinal thickness and any other variable evaluated. Findings of this cohort study suggest that smaller optic cup morphology may be associated with optic disc edema development during spaceflight. Crew members with this cup profile may benefit from enhanced ophthalmic monitoring during spaceflight and use of countermeasures against spaceflight-associated neuro-ocular syndrome.

Protective effect of TPP-Niacin on microgravity-induced oxidative stress and mitochondrial dysfunction of retinal epithelial cells

Adverse effects of spaceflight on the human body are attritubuted to microgravity and space radiation. One of the most sensitive organs affected by them is the eye, particularly the retina. The conditions that astronauts suffer, such as visual acuity, is collectively called a spaceflight-associated neuro-ocular syndrome (SANS); however, the underlying molecular mechanism of the microgravity-induced ocular pathogenesis is not clearly understood. The current study explored how microgravity affects the retina function in ARPE19 cells in vitro under time-averaged simulated microgravity (μG) generated by clinostat. We found multicellular spheroid (MCS) formation and a significantly decreased cell migration potency under μG conditions compared to 1G in ARPE19 cells. We also observed that μG increases intracellular reactive oxygen species (ROS) and causes mitochondrial dysfunction in ARPE19 cells. Subsequently, we showed that μG activates autophagic pathways and ciliogenesis. Furthermore, we demonstrated that mitophagy activation is triggered via the mTOR-ULK1-BNIP3 signaling axis. Finally, we validated the effectiveness of TPP-Niacin in mitigating μG-induced oxidative stress and mitochondrial dysfunction in vitro, which provides the first experimental evidence for TPP-Niacin as a potential therapeutic agent to ameliorate the cellular phenotypes caused by μG in ARPE19 cells. Further investigations are, however, required to determine its physiological functions and biological efficacies in primary human retinal cells, in vivo models, and target identification.

Future research directions to identify risks and mitigation strategies for neurostructural, ocular, and behavioral changes induced by human spaceflight: A NASA-ESA expert group consensus report.

A team of experts on the effects of the spaceflight environment on the brain and eye (SANS: Spaceflight-Associated Neuro-ocular Syndrome) was convened by NASA and ESA to (1) review spaceflight-associated structural and functional changes of the human brain and eye, and any interactions between the two; and (2) identify critical future research directions in this area to help characterize the risk and identify possible countermeasures and strategies to mitigate the spaceflight-induced brain and eye alterations. The experts identified 14 critical future research directions that would substantially advance our knowledge of the effects of spending prolonged periods of time in the spaceflight environment on SANS, as well as brain structure and function. They used a paired comparison approach to rank the relative importance of these 14 recommendations, which are discussed in detail in the main report and are summarized briefly below.

Antioxidants Derived from Natural Products Reduce Radiative Damage in Cultured Retinal Glia to Prevent Oxidative Stress

Retinal pathologies have been heavily studied in response to radiation and microgravity, including spaceflight-associated neuro-ocular syndrome (SANS), which is commonly developed in space flight. SANS has been characterized in clinical studies of astronauts returning to Earth and includes a range of symptoms, such as globe flattening, optic-disc edema, retinal folds, and retinal ischemia. In cases of retinal insult, Müller glia (MG) cells respond via neuroprotective gliotic responses that may become destructive to produce glial scarring and vison loss over time. Retinal pathology is further impacted by the production of excessive reactive oxygen species (ROS) that stimulate retinal inflammation and furthers the gliosis of MG. Neuroprotectants derived from natural products (NPs) able to scavenge excess ROS and mitigate long-term, gliotic responses have garnered recent interest, especially among mature and aging adults. The natural antioxidants aloin and ginkgolide A flavonoids, derived from Aloe vera and Ginkgo biloba species, respectively, have been of particular interest due to their recent use in other nervous-system studies. The current study examined MG behaviors in response to different doses of aloin and ginkgolide A over time by measuring changes in morphology, survival, and ROS production within microscale assays. The study was further enhanced by using galactic cosmic rays (GCR) at the Brookhaven NASA Space Radiation Laboratory to simulate ionizing radiation in low- and high-radiation parameters. Changes in the survival and ROS production of radiation-treated MG were then measured in response to varying dosage of NPs. Our study used in vitro systems to evaluate the potential of NPs to reduce oxidative stress in the retina, highlighting the underexplored interplay between NP antioxidants and MG endogenous responses both in space and terrestrially.

Changes in Optic Nerve Head and Retinal Morphology During Spaceflight and Acute Fluid Shift Reversal

Countermeasures that reverse the headward fluid shift experienced in weightlessness have the potential to mitigate spaceflight-associated neuro-ocular syndrome. This study investigated whether use of the countermeasure lower-body negative pressure during spaceflight was associated with changes in ocular structure. To determine whether changes to the optic nerve head and retina during spaceflight can be mitigated by brief in-flight application of 25-mm Hg lower-body negative pressure. In the National Aeronautics and Space Administration's "Fluid Shifts Study," a prospective cohort study, optical coherence tomography scans of the optic nerve head and macula were obtained from US and international crew members before flight, in-flight, and up to 180 days after return to Earth. In-flight scans were obtained both under normal weightless conditions and 10 to 20 minutes into lower-body negative pressure exposure. Preflight and postflight data were collected in the seated, supine, and head-down tilt postures. Crew members completed 6- to 12-month missions that took place on the International Space Station. Data were analyzed from 2016 to 2021. Spaceflight and lower-body negative pressure. Changes in minimum rim width, optic cup volume, Bruch membrane opening height, peripapillary total retinal thickness, and macular thickness. Mean (SD) flight duration for the 14 crew members (mean [SD] age, 45 [6] years; 11 male crew members [79%]) was 214 (72) days. Ocular changes on flight day 150, as compared with preflight seated, included an increase in minimum rim width (33.8 μm; 95% CI, 27.9-39.7 μm; P < .001), decrease in cup volume (0.038 mm3; 95% CI, 0.030-0.046 mm3; P < .001), posterior displacement of Bruch membrane opening (-9.0 μm; 95% CI, -15.7 to -2.2 μm; P = .009), and decrease in macular thickness (fovea to 500 μm, 5.1 μm; 95% CI, 3.5-6.8 μm; P < .001). Brief exposure to lower-body negative pressure did not affect these parameters. Results of this cohort study suggest that peripapillary tissue thickening, decreased cup volume, and mild central macular thinning were associated with long-duration spaceflight. Acute exposure to 25-mm Hg lower-body negative pressure did not alter optic nerve head or retinal morphology, suggesting that longer durations of a fluid shift reversal may be needed to mitigate spaceflight-induced changes and/or other factors are involved.

Non-Invasive Intracranial Pressure Monitoring and Its Applicability in Spaceflight.

INTRODUCTION: Neuro-ophthalmic findings collectively defined as Spaceflight-Associated Neuro-ocular Syndrome (SANS) are one of the leading health priorities in astronauts engaging in long duration spaceflight or prolonged microgravity exposure. Though multifactorial in etiology, similarities to terrestrial idiopathic intracranial hypertension (IIH) suggest these changes may result from an increase or impairing in intracranial pressure (ICP). Finding a portable, accessible, and reliable method of monitoring ICP is, therefore, crucial in long duration spaceflight. A review of recent literature was conducted on the biomedical literature search engine PubMed using the search term "non-invasive intracranial pressure". Studies investigating accuracy of noninvasive and portable methods were assessed. The search retrieved different methods that were subsequently grouped by approach and technique. The majority of publications included the use of ultrasound-based methods with variable accuracies. One of which, noninvasive ICP estimation by optical nerve sheath diameter measurement (nICP_ONSD), presented the highest statistical correlation and prediction values to invasive ICP, with area under the curve (AUC) ranging from 0.75 to 0.964. One study even considers a combination of ONSD with transcranial Doppler (TCD) for an even higher performance. Other methods, such as near-infrared spectroscopy (NIRS), show positive and promising results [good statistical correlation with invasive techniques when measuring cerebral perfusion pressure (CPP): r = 0.83]. However, for its accessibility, portability, and accuracy, ONSD seems to present itself as the up to date, most reliable, noninvasive ICP surrogate and a valuable spaceflight asset.Félix H, Santos Oliveira E. Non-invasive intracranial pressure monitoring and its applicability in spaceflight. Aerosp Med Hum Perform. 2022; 93(6):517-531.

Simulated microgravity promotes oxidative stress-induced apoptosis in ARPE-19 cells associated with Nrf2 signaling pathway

Spaceflight associated neuro-ocular syndrome (SANS) has become a high-risk complication for astronauts in the microgravity environment. Growing evidences suggest that altered hemodynamics of the cerebrospinal fluid system under microgravity may affect optic nerve-related structures and lead to ocular diseases. Retinal pigment epithelial (RPE) cells play a pivotal role in maintaining the blood-retinal barrier, participating in the metabolism of visual circulation. Previous study has observed that the structure, shape, adhesion, migration and angiogenesis of RPE cells were significantly changed under microgravity. However, the interrelated molecular mechanisms underlying the cytological functions of RPE cells under microgravity have yet to be elucidated. Here, we exposed ARPE-19 cells in Random Positioning Machine (RPM) system. The preliminary analysis of cytological functions found that the viability of ARPE-19 cells was decreased and the cell cycle was arrested in S phase. Further results revealed that elevated ROS in microgravity caused oxidative stress, resulting in the activation of the Nrf2-HO-1 pathway. Meanwhile, cells subjected to oxidative damage result in apoptosis by regulating the expression of apoptosis-related genes. Taken together, these findings have significant implications for the understanding the molecular mechanism of SANS.

Longitudinal MRI-visible perivascular space (PVS) changes with long-duration spaceflight.

Humans are exposed to extreme environmental stressors during spaceflight and return with alterations in brain structure and shifts in intracranial fluids. To date, no studies have evaluated the effects of spaceflight on perivascular spaces (PVSs) within the brain, which are believed to facilitate fluid drainage and brain homeostasis. Here, we examined how the number and morphology of magnetic resonance imaging (MRI)-visible PVSs are affected by spaceflight, including prior spaceflight experience. Fifteen astronauts underwent six T1-weighted 3 T MRI scans, twice prior to launch and four times following their return to Earth after ~ 6-month missions to the International Space Station. White matter MRI-visible PVS number and morphology were calculated using an established, automated segmentation algorithm. We validated our automated segmentation algorithm by comparing algorithm PVS counts with those identified by two trained raters in 50 randomly selected slices from this cohort; the automated algorithm performed similarly to visual ratings (r(48) = 0.77, p < 0.001). In addition, we found high reliability for four of five PVS metrics across the two pre-flight time points and across the four control time points (ICC(3,k) > 0.50). Among the astronaut cohort, we found that novice astronauts showed an increase in total PVS volume from pre- to post-flight, whereas experienced crewmembers did not (p = 0.020), suggesting that experienced astronauts may exhibit holdover effects from prior spaceflight(s). Greater pre-flight PVS load was associated with more prior flight experience (r = 0.60–0.71), though these relationships did not reach statistical significance (p > 0.05). Pre- to post-flight changes in ventricular volume were not significantly associated with changes in PVS characteristics, and the presence of spaceflight associated neuro-ocular syndrome (SANS) was not associated with PVS number or morphology. Together, these findings demonstrate that PVSs can be consistently identified on T1-weighted MRI scans, and that spaceflight is associated with PVS changes. Specifically, prior spaceflight experience may be an important factor in determining PVS characteristics.

Does Long-Duration Exposure to Microgravity Lead to Dysregulation of the Brain and Ocular Glymphatic Systems?

Spaceflight-associated neuro-ocular syndrome (SANS) has been well documented in astronauts both during and after long-duration spaceflight and is characterized by the development of optic disc edema, globe flattening, choroidal folds, and hyperopic refractive error shifts. The exact mechanisms underlying these ophthalmic abnormalities remain unclear. New findings regarding spaceflight-associated alterations in cerebrospinal fluid spaces, specifically perivascular spaces, may shed more light on the pathophysiology of SANS. The preliminary results of a recent brain magnetic resonance imaging study show that perivascular spaces enlarge under prolonged microgravity conditions, and that the amount of fluid in perivascular spaces is linked to SANS. The exact pathophysiological mechanisms underlying enlargement of perivascular spaces in space crews are currently unclear. Here, we speculate that the dilation of perivascular spaces observed in long-duration space travelers may result from impaired cerebral venous outflow and compromised cerebrospinal fluid resorption, leading to obstruction of glymphatic perivenous outflow and increased periarterial cerebrospinal fluid inflow, respectively. Further, we provide a possible explanation for how dilated perivascular spaces can be associated with SANS. Given that enlarged perivascular spaces in space crews may be a marker of altered venous hemodynamics and reduced cerebrospinal fluid outflow, at the level of the optic nerve and eye, these disturbances may contribute to SANS. If confirmed by further studies, brain glymphatic dysfunction in space crews could potentially be considered a risk factor for the development of neurodegenerative diseases, such as Alzheimer’s disease. Furthermore, long-duration exposure to microgravity might contribute to SANS through dysregulation of the ocular glymphatic system. If prolonged spaceflight exposure causes disruption of the glymphatic systems, this might affect the ability to conduct future exploration missions, for example, to Mars. The considerations outlined in the present paper further stress the crucial need to develop effective long-term countermeasures to mitigate SANS-related physiologic changes during long-duration spaceflight.

Optic Disc Edema in Astronauts from a Choroidal Point of View.

INTRODUCTION: Optic disc edema has been well documented in astronauts both during and after long-duration spaceflight and is hypothesized to largely result from increased pressure within the orbital subarachnoid space brought about by a generalized rise in intracranial pressure or from sequestration of cerebrospinal fluid within the orbital subarachnoid space with locally elevated optic nerve sheath pressure. In addition, a recent prospective study documented substantial spaceflight-associated peripapillary choroidal thickening, which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. In the present article, based on the above, we offer a new perspective on the pathogenesis of microgravity-induced optic disc edema from a choroidal point of view. We propose that prolonged microgravity exposure may result in the transudation of fluid from the choroidal vasculature, which, in turn, may reach the optic nerve head, and ultimately may lead to fluid stasis within the prelaminar region secondary to impaired ocular glymphatic outflow. If confirmed, this viewpoint would shed new light on the development of optic disc edema in astronauts.Wostyn P, Gibson CR, Mader TH. Optic disc edema in astronauts from a choroidal point of view. Aerosp Med Hum Perform. 2022; 93(4):396-398.

A theory for why the spaceflight-associated neuro-ocular syndrome develops.

A theory for why the spaceflight-associated neuro-ocular syndrome develops.

Spaceflight-associated neuro-ocular syndrome: a review of potential pathogenesis and intervention.

With the continuing progress in space exploration, a new and perplexing condition related to spaceflight ocular syndrome has emerged in the past four decades. National Aeronautics and Space Administration (NASA) has named this condition "spaceflight-associated neuro-ocular syndrome" (SANS). This article gives an overview of the current research about SANS and traditional Chinese medicine (TCM) by analyzing the existing publications on PubMed and CNKI and reports from NASA about SANS, summarizing the potential pathogenesis of SANS and physical interventions for treating SANS, and discussing the feasibility of treating SANS with TCM. Due to the unique characteristics of the space environment, it is infeasible to conduct large-scale human studies of SANS. SANS may be the result of the interaction of multiple factors, including inflammation and fluid displacement in the optic nerve sheath and cerebrospinal fluid. We should pay attention to SANS. Visual function is not only related to the health of astronauts but also closely related to space operations. TCM has antioxidative stress and antiapoptotic effects and is widely used for optic nerve diseases. TCM has great potential to prevent SANS.

How spaceflight challenges human cardiovascular health.

The harsh environmental conditions in space, particularly weightlessness and radiation exposure, can negatively affect cardiovascular function and structure. In the future, preventive cardiology will be crucial in enabling safe space travel. Indeed, future space missions destined to the Moon and from there to Mars will create new challenges to cardiovascular health while limiting medical management. Moreover, commercial spaceflight evolves rapidly such that older persons with cardiovascular risk factors will be exposed to space conditions. This review provides an overview on studies conducted in space and terrestrial models, particularly head-down bedrest studies. These studies showed that weightlessness elicits a fluid shift towards the head, which likely predisposes to the spaceflight-associated neuro-ocular syndrome, neck vein thrombosis, and orthostatic intolerance after return to Earth. Moreover, cardiovascular unloading produces cardiopulmonary deconditioning, which may be associated with cardiac atrophy. In addition to limiting physical performance, the mechanism further worsens orthostatic tolerance after return to Earth. Finally, space conditions may directly affect vascular health; however, the clinical relevance of these findings in terms of morbidity and mortality is unknown. Targeted preventive measures, which are referred to as countermeasures in aerospace medicine, and technologies to identify vascular risks early on will be required to maintain cardiovascular performance and health during future space missions.

Contributed Session I: A Multi-Modal Visual Assessment System For Monitoring Spaceflight Associated Neuro-Ocular Syndrome (SANS) During Long Duration Spaceflight

Spaceflight Associated Neuro-Ocular Syndrome (SANS) refers to a unique collection of neuro-ophthalmic clinical and imaging findings that are observed in astronauts during long duration spaceflight. These findings include optic disc edema, posterior globe flattening, retinal nerve layer fiber thickening, optic nerve sheath distension, and hyperopic shift. SANS currently serves as a large barrier to deep space exploration; however, the exact pathophysiology is still being investigated. While in-flight imaging exists on the International Space Station, there are limitations to constant monitoring. To efficiently document the subtle changes that occur in SANS, NASA has funded the development of a head-mounted display, multi-modal visual assessment system; this novel device integrates visual acuity, visual field, contrast sensitivity, and metamorphopsia data (indirect indications) with known terrestrial neuro-ophthalmic imaging (direct indications) from astronauts and terrestrial analogs. By mapping these two indications, this visual assessment device will provide rapid in-flight monitoring of SANS symptoms and provide tools for the terrestrial development of countermeasures. We are in the process of beginning a pilot study of this multi-modal visual assessment device in healthy subjects to investigate the validity and reliability of this novel technology. This foundational study will compare the system with standard vision assessments utilized in clinical practice.

The Effects of Space Radiation and Microgravity on Ocular Structures

Long-term exposure to microgravity and space radiation leads to physiological and pathological changes in human biology. Pathological neuro-ocular changes are collected under the name spaceflight-associated neuro-ocular syndrome. This review examines studies on the effects of microgravity and space radiation on the ocular structures and their results. In addition, we discuss treatment methods and hypotheses to reduce the effects of microgravity and space radiation on biological structures.

Head-mounted digital metamorphopsia suppression as a countermeasure for macular-related visual distortions for prolonged spaceflight missions and terrestrial health.

During long-duration spaceflight, astronauts are exposed to various risks including spaceflight-associated neuro-ocular syndrome, which serves as a risk to astronaut vision and a potential physiological barrier to future spaceflight. When considering exploration missions that may expose astronauts to longer periods of microgravity, radiation exposure, and natural aging processes during spaceflight, more severe changes to functional vision may occur. The macula plays a critical role in central vision and disruptions to this key area in the eye may compromise functional vision and mission performance. In this article, we describe the development of a countermeasure technique to digitally suppress monocular central visual distortion with head-mounted display technology. We report early validation studies with this noninvasive countermeasure in individuals with simulated metamorphopsia. When worn by these individuals, this emerging wearable countermeasure technology has demonstrated a suppression of monocular visual distortion. We describe the considerations and further directions of this head-mounted technology for both astronauts and aging individuals on Earth.

Effect of Nightly Lower Body Negative Pressure on Choroid Engorgement in a Model of Spaceflight-Associated Neuro-ocular Syndrome

Astronauts returning from long-duration spaceflight experience ocular remodeling related to cephalad fluid shifts induced by microgravity. It is hypothesized that the absence of diurnal reductions in intracranial pressure in microgravity creates a low but persistent pressure gradient at the posterior aspect of the eye, which results in ocular remodeling and space-associated neuro-ocular syndrome (SANS) over many months. To determine whether partial reintroduction of footward fluid shifts during simulated microgravity via lower body negative pressure (LBNP) during sleep attenuates choroid engorgement, an early marker of ocular remodeling related to SANS. Between May 2019 and February 2020, participants with no major cardiovascular, kidney, or ophthalmic disease completed 3 days of supine (0°) bed rest with and 3 days without 8 hours of nightly LBNP in a randomized, crossover design. This single-center investigation took place at the UT Southwestern Medical Center. All analyses were conducted blinded to condition and time point. Eight hours of nightly LBNP (-20 mm Hg) vs no LBNP. The primary outcome was the change in choroid area and volume after 3 days of bed rest measured by optical coherence tomography. Of 10 participants, 5 were female, the mean (SD) age was 29 (9) years, and the age range was 18 to 55 years. Central venous pressure increased from the seated to supine position (mean [SD], seated: -2.3 [2.0] vs supine: 6.9 [2.0] mm Hg; P < .001), leading to choroid engorgement over 3 days of bed rest (Δ area: +0.09 mm2 [95% CI, 0.04-0.13]; P = .001; Δ volume: +0.37 mm3 [95% CI, 0.19-0.55]; P = .001). Nightly LBNP caused a sustained reduction in supine central venous pressure (mean [SD], 5.7 [2.2] mm Hg to 1.2 [1.4 mm Hg]; P < .001) and attenuated the increase in choroid area (74%) (Δ: 0.02 mm2 [95% -0.02 to 0.06]; P = .01) and volume (53%) (Δ: 0.17 mm3 [95% CI, 0.01-0.34]; P = .05) compared with control. Nightly LBNP reinstated a footward fluid shift and mitigated the increase in choroid area and volume. LBNP during sleep may be an effective countermeasure for ocular remodeling and SANS during long-duration space missions.