RESUMEN

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

RESUMEN

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 if 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 six-degree 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-minute intermittent AG (iAG), and daily 30-minute 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 3T. MRI was performed at baseline, 14 and 52 days into HDTBR, and three 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 to 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 to HDTBR alone, indicating that thirty minutes 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.

RESUMEN

With plans for future long-duration crewed exploration, NASA has identified several high priority potential health risks to astronauts in space. One such risk is a collection of neurologic and ophthalmic findings termed spaceflight associated neuro-ocular syndrome (SANS). The findings of SANS include optic disc edema, globe flattening, retinal nerve fiber layer thickening, chorioretinal folds, hyperopic shifts, and cotton-wool spots. The cause of SANS was initially thought to be a cephalad fluid shift in microgravity leading to increased intracranial pressure, venous stasis and impaired CSF outflow, but the precise etiology of SANS remains ill defined. Recent studies have explored multiple possible pathogenic mechanisms for SANS including genetic and hormonal factors; a cephalad shift of fluid into the orbit and brain in microgravity; and disruption to the brain glymphatic system. Orbital, ocular, and cranial imaging, both on Earth and in space has been critical in the diagnosis and monitoring of SANS (e.g., fundus photography, optical coherence tomography (OCT), magnetic resonance imaging (MRI), and orbital/cranial ultrasound). In addition, we highlight near-infrared spectroscopy and diffusion tensor imaging, two newer modalities with potential use in future studies of SANS. In this manuscript we provide a review of these modalities, outline their current and potential use in space and on Earth, and review the reported major imaging findings in SANS.

Asunto(s)

RESUMEN

Long-duration spaceflight (LDSF) is associated with unique hazards and linked with numerous human health risks including Spaceflight Associated Neuro-ocular Syndrome (SANS). The proposed mechanisms for SANS include microgravity induced cephalad fluid shift and increased Intracranial Pressure (ICP). SANS is a disorder seen only after LDSF and has no direct terrestrial pathologic counterpart as the zero G environment cannot be completely replicated on Earth. Head-down tilt, bed rest studies however have been used as a terrestrial analog and produce the cephalad fluid shift. Some proposed countermeasures for SANS include vasoconstrictive thigh cuffs and lower body negative pressure. Another potential researched countermeasure is the impedance threshold device (ITD) which can reduce ICP. We review the mechanisms of the ITD and its potential use as a countermeasure for SANS.

Asunto(s)

Asunto(s)

RESUMEN

Purpose: To provide an automated system for synthesizing fluorescein angiography (FA) images from color fundus photographs for averting risks associated with fluorescein dye and extend its future application to spaceflight associated neuro-ocular syndrome (SANS) detection in spaceflight where resources are limited. Design: Development and validation of a novel conditional generative adversarial network (GAN) trained on limited amount of FA and color fundus images with diabetic retinopathy and control cases. Participants: Color fundus and FA paired images for unique patients were collected from a publicly available study. Methods: FA4SANS-GAN was trained to generate FA images from color fundus photographs using 2 multiscale generators coupled with 2 patch-GAN discriminators. Eight hundred fifty color fundus 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 3 other GAN architectures trained on the same data set. Furthermore, we test the robustness of the models against acquisition noise and retaining structural information when introduced to artificially created biological markers. Main Outcome Measures: For GAN synthesis, metric Fréchet Inception Distance (FID) and Kernel Inception Distance (KID). Also, two 1-sided tests (TOST) based on Welch's t test for measuring statistical significance. Results: On test FA images, mean FID for FA4SANS-GAN was 39.8 (standard deviation, 9.9), which is better than GANgio model's mean of 43.2 (standard deviation, 13.7), Pix2PixHD's mean of 57.3 (standard deviation, 11.5) and Pix2Pix's mean of 67.5 (standard deviation, 11.7). Similarly for KID, FA4SANS-GAN achieved mean of 0.00278 (standard deviation, 0.00167) which is better than other 3 model's mean KID of 0.00303 (standard deviation, 0.00216), 0.00609 (standard deviation, 0.00238), 0.00784 (standard deviation, 0.00218). For TOST measurement, FA4SANS-GAN was proven to be statistically significant versus GANgio (P = 0.006); versus Pix2PixHD (P < 0.00001); and versus Pix2Pix (P < 0.00001). Conclusions: Our study has shown FA4SANS-GAN to be statistically significant for 2 GAN synthesis metrics. Moreover, it is robust against acquisition noise, and can retain clear biological markers compared with the other 3 GAN architectures. This deployment of this model can be crucial in the International Space Station for detecting SANS. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

RESUMEN

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.

RESUMEN

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.

RESUMEN

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.

Asunto(s)

RESUMEN

The translaminar pressure gradient (TLPG) refers to two forces at the lamina cribosa of the optic nerve: the anteriorly acting intracranial pressure (ICP), and posteriorly-acting intraocular pressure (IOP). It has been proposed that controlling the translaminar pressure gradient at regular intervals may preserve the optic nerve and slow the course of glaucoma. The precisional modulation of this TLPG is a recently introduced concept that may play a role in the treatment of ophthalmic diseases such as glaucoma. In this manuscript, we review the applications of pressurized goggles on ophthalmic diseases. We also elaborate upon current investigations in modulation of the TLPG including goggles and the multi-pressure dial goggle. We discuss future research directions for ophthalmic diseases including spaceflight associated neuro-ocular syndrome (SANS), a large physiological barrier to future long-duration spaceflight.

RESUMEN

Spaceflight associated neuro-ocular syndrome (SANS) is a unique phenomenon that has been observed in astronauts who have undergone long-duration spaceflight (LDSF). The syndrome is characterized by distinct imaging and clinical findings including optic disc edema, hyperopic refractive shift, posterior globe flattening, and choroidal folds. SANS serves a large barrier to planetary spaceflight such as a mission to Mars and has been noted by the National Aeronautics and Space Administration (NASA) as a high risk based on its likelihood to occur and its severity to human health and mission performance. While it is a large barrier to future spaceflight, the underlying etiology of SANS is not well understood. Current ophthalmic imaging onboard the International Space Station (ISS) has provided further insights into SANS. However, the spaceflight environment presents with unique challenges and limitations to further understand this microgravity-induced phenomenon. The advent of artificial intelligence (AI) has revolutionized the field of imaging in ophthalmology, particularly in detection and monitoring. In this manuscript, we describe the current hypothesized pathophysiology of SANS and the medical diagnostic limitations during spaceflight to further understand its pathogenesis. We then introduce and describe various AI frameworks that can be applied to ophthalmic imaging onboard the ISS to further understand SANS including supervised/unsupervised learning, generative adversarial networks, and transfer learning. We conclude by describing current research in this area to further understand SANS with the goal of enabling deeper insights into SANS and safer spaceflight for future missions.

RESUMEN

The National Aeronautics and Space Administration (NASA) has rigorously documented a group of neuro-ophthalmic findings in astronauts during and after long-duration spaceflight known as spaceflight associated neuro-ocular syndrome (SANS). For astronaut safety and mission effectiveness, understanding SANS and countermeasure development are of utmost importance. Although the pathogenesis of SANS is not well defined, a leading hypothesis is that SANS might relate to a sub-clinical increased intracranial pressure (ICP) from cephalad fluid shifts in microgravity. However, no direct ICP measurements are available during spaceflight. To further understand the role of ICP in SANS, pupillometry can serve as a promising non-invasive biomarker for spaceflight environment as ICP is correlated with the pupil variables under illumination. Extended reality (XR) can help to address certain limitations in current methods for efficient pupil testing during spaceflight. We designed a protocol to quantify parameters of pupil reactivity in XR with an equivalent time duration of illumination on each eye compared to pre-existing, non-XR methods. Throughout the assessment, the pupil diameter data was collected using HTC Vive Pro-VR headset, thanks to its eye-tracking capabilities. Finally, the data was used to compute several pupil variables. We applied our methods to 36 control subjects. Pupil variables such as maximum and minimum pupil size, constriction amplitude, average constriction amplitude, maximum constriction velocity, latency and dilation velocity were computed for each control data. We compared our methods of calculation of pupil variables with the non-XR methods existing in the literature. Distributions of the pupil variables such as latency, constriction amplitude, and velocity of 36 control data displayed near-identical results from the non-XR literature for normal subjects. We propose a new method to evaluate pupil reactivity with XR technology to further understand ICP's role in SANS and provide further insight into SANS countermeasure development for future spaceflight.

Asunto(s)

RESUMEN

Spaceflight associated neuro-ocular syndrome (SANS) is one of the potential barriers to human long-duration spaceflight (LDSF), including a manned mission to Mars. While a large barrier, the pathophysiology of SANS is not well understood, and functional and structural findings from SANS continue to be further characterized. Currently on the International Space Station (ISS), scheduled visual assessments are static visual acuity, Amsler grid, and a self-reported survey. Additional visual assessments may help the understanding of this neuro-ophthalmic phenomenon, as well as the effects of spaceflight of overall ocular health. In this paper, a case is made for expanding scheduled visual assessments to include dynamic visual, contrast sensitivity (CS), visual field testing, and virtual reality-based metamorphopsia assessment during spaceflight. These further assessments may play a key role in helping to determine the structural and functional changes associated with SANS, which are crucial to maintain astronaut vision during LDSF, as well as for developing countermeasures. Finally, a brief discussion is provided about current challenges to expanding visual testing during spaceflight and potential solutions to these barriers, specifically head-mounted visual assessment technology.

Asunto(s)

RESUMEN

In anticipation of space exploration where astronauts are traveling away from Earth, and for longer durations with an increasing communication lag, artificial intelligence (AI) frameworks such as large language learning models (LLMs) that can be trained on Earth can provide real-time answers. This emerging technology may be helpful for acute medical emergencies, particularly in austere and distant space environments. In this manuscript, we provide an overview of generative pre-trained transformer (GPT) technology, a rapidly emerging AI technology, and implications, considerations, and limitations of such technology for space health.

Asunto(s)

RESUMEN

Spaceflight-Associated Neuro-ocular Syndrome (SANS) is a descriptor of several ocular and visual signs and symptoms which commonly afflicts those exposed to microgravity. We propose a new theory for the driving force leading to the development of Spaceflight-Associated Neuro-ocular Syndrome which is described via a finite element model of the eye and orbit. Our simulations suggest that the anteriorly directed force produced by orbital fat swelling is a unifying explanatory mechanism for Spaceflight-Associated Neuro-ocular Syndrome, as well as producing a larger effect than that generated by elevation in intracranial pressure. Hallmarks of this new theory include broad flattening of the posterior globe, loss of tension in the peripapillary choroid, decreased axial length, consistent with findings in astronauts. A geometric sensitivity study suggests several anatomical dimensions may be protective against Spaceflight-Associated Neuro-ocular Syndrome.

Asunto(s)

RESUMEN

BACKGROUND: "Spaceflight associated neuro-ocular syndrome" (SANS) represents a challenging health condition in modern space medicine. Forty-eight percent of astronauts are diagnosed with SANS after long-term space missions. The pathophysiological mechanism seems to be multifactorial, and yet remains unknown. In this proof-of-concept study we plan to investigate retinal microcirculatory changes in weightlessness and aim to identify their role in the development of SANS. METHODS AND DESIGN: Healthy individuals will take part in a parabolic flight campaign, which recreates fractioned total weightlessness periods. The airplane is specifically equipped, and designed for the execution of parabolic flight maneuvers and scientific research in microgravity. Retinal microcirculation will be assessed with a modified fundus camera, which allows dynamic vessel analysis. We will additionally measure intra-ocular pressure and hemodynamic changes during each phase of the flight. Blood samples will be analyzed at baseline, one hour and 24 hours after exposure to weightlessness. CONCLUSIONS: This pilot study aims to investigate the feasibility of retinal microcirculation assessment during varying gravity. Results of this study may generate insights whether venous stasis in the eye, surrogated by the dilatation of retinal vessels and increase in intraocular pressure as signs of venous insufficiency, may potentially contribute to the development of SANS.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Introduction: Entry into weightlessness results in a fluid shift and a loss of hydrostatic gradients. These factors are believed to affect the eye and contribute to the ocular changes that occur in space. We measured eye parameters during fluid shifts produced by lower body negative pressure (LBNP) and lower body positive pressure (LBPP) and changes in hydrostatic gradient direction (supine-prone) in normal subjects to assess the relative effects of fluid shifts and hydrostatic gradient changes on the eye. Methods: Ocular parameters (intraocular pressure (IOP), ocular geometry, and optical coherence tomography measures) were measured in the seated, supine, and prone positions. To create a fluid shift in the supine and prone positions, the lower body chamber pressure ranged from -40 mmHg to +40 mmHg. Subjects maintained each posture and LBNP/LBPP combination for 15 min prior to data collection. A linear mixed-effects model was used to determine the effects of fluid shifts (as reflected by LBNP/LBPP) and hydrostatic gradient changes (as reflected by the change from seated to supine and from seated to prone) on eye parameters. Results: Chamber pressure was positively correlated with both increased choroidal thickness (ß = 0.11 , p = 0.01) and IOP (ß = 0.06 p < 0.001). The change in posture increased IOP compared to seated IOP (supine ß = 2.1, p = 0.01, prone ß = 9.5, p < 0.001 prone) but not choroidal thickness. IOP changes correlated with axial length (R = 0.72, p < 0.001). Discussion: The effects of hydrostatic gradients and fluids shifts on the eye were investigated by inducing a fluid shift in both the supine and prone postures. Both hydrostatic gradients (posture) and fluid shifts (chamber pressure) affected IOP, but only hydrostatic gradients affected axial length and aqueous depth. Changes in choroidal thickness were only significant for the fluid shifts. Changes in hydrostatic gradients can produce significant changes in both IOP and axial length. Fluid shifts are often cited as important factors in the pathophysiology of SANS, but the local loss of hydrostatic gradients in the head may also play an important role in these ocular findings.