The Case for Expanding Visual Assessments During Spaceflight

Spaceflight associated neuro-ocular syndrome (SANS) alters the vision of astronauts during long-duration spaceflights. There is controversy regarding SANS being similar to patients with idiopathic intracranial hypertension (IIH). IIH has been shown to be due to an elevation in venous sinus pressure. The literature suggests an increase in jugular vein pressure secondary to a headward shift of fluid occurs in SANS but this may not be enough to significantly alter the intracranial pressure (ICP). The literature regarding cardiac output and cerebral blood flow (CBF) in long-duration spaceflight is contradictory, however, more recent data suggests increased flow. Recent modelling has shown that an increase in CBF can significantly increase sinus pressure. The purpose of the present paper is to review the SANS vascular dynamics literature and through mathematical modelling suggest the possible underlying cause of SANS as an elevation in venous sinus pressure, secondary to the redistribution of fluids towards the head, together with a significant increase in pressure drop across the venous system related to the CBF.

A unique constellation of ocular structural changes and visual anomalies known as Spaceflight Associated Neuro-ocular Syndrome (SANS) affects 70 % of crew members after long-duration spaceflight. Current hypotheses regarding the etiology of SANS discuss cephalad fluid shifts and venous congestion, which are correlated with elevated intra-cranial pressure (ICP) and enlarged perivascular spaces (PVS). These PVS comprise the glymphatic system (GS), a recently discovered network of influx and efflux pathways for cerebrospinal fluid (CSF) and metabolites in the central nervous system (CNS). Both glymphatic clearance and traditionally understood CSF circulation are affected by sleep-wake cycles, displaying a significant increase in fluid flow during sleep. Natural sleep has been associated with a 60 % increase in interstitial space in animal studies, which likely enhances GS exchange and outflow. Corresponding studies in humans using contrast-enhanced MRI associate sleep with greater glymphatic clearance compared to wakefulness. The sleep problems of astronauts during long-duration spaceflight have been well documented, ranging from sleep disruption and decreased quality to insufficient sleep duration. With recent terrestrial studies providing evidence that sleep deprivation impairs molecular clearance from the human brain, it follows that similar glymphatic dysfunction may arise due to these conditions in astronauts. Thus, in addition to impairing crew member work performance on long-duration space missions, sleep deprivation may exert long-term neuro-ocular effects via decreased glymphatic efficiency and clearance. The adverse impact of the resulting cognitive and visual disturbances presents a major future performance risk to astronauts. This work discusses the existing body of literature regarding the connections between circadian disruption and glymphatic disruption as a potential contributing mechanism for the development of SANS. This association should receive focused attention in future research as a potential risk factor for SANS. In addition, interventions that enhance extraterrestrial sleep quality and duration may prove to be practical countermeasures for the prevention of this syndrome.

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

Re: Stenger et al.: Focus on the optic nerve head in spaceflight-associated neuro-ocular syndrome (Ophthalmology. 2019;126:1604–1606)

During long-duration spaceflights, nearly all astronauts exhibit some change in ocular structure within the spectrum of spaceflight-associated neuro-ocular syndrome. To quantitatively determine in a prospective study whether changes in ocular structures hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome occur during 6-month missions on board the International Space Station (ISS). The Ocular Health ISS Study of astronauts is a longitudinal prospective cohort study that uses objective quantitative imaging modalities. The present cohort study investigated the ocular structure of 11 astronauts before, during, and after a 6-month mission on board the ISS. Changes in ocular structure (peripapillary edema, axial length, anterior chamber depth, and refraction) hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome during 6-month missions on board the ISS were assessed. Statistical analyses were conducted from August 2018 to January 2019. Before launch, the 11 astronauts were a mean (SD) age of 45 (5) years, a mean (SD) height of 1.76 (0.05) m, and a mean (SD) weight of 75.3 (7.1) kg. Six astronauts did not have prior spaceflight experience, 3 had completed short-duration missions on board the Space Shuttle, and 2 had previous long-duration spaceflight missions on board the ISS. Their mean (SD) duration on board the ISS in the present study was 170 (19) days. Optic nerve head rim tissue and peripapillary choroidal thickness increased from preflight values during early spaceflight, with maximal change typically near the end of the mission (mean change in optic nerve head rim tissue thickness on flight day 150: 35.7 μm; 95% CI, 28.5-42.9 μm; P < .001; mean choroidal thickness change on flight day 150: 43 μm; 95% CI, 35-46 μm; P < .001). The mean postflight axial length of the eye decreased by 0.08 mm (95% CI, 0.10-0.07 mm; P < .001) compared with preflight measures, and this change persisted through the last examination (1 year after spaceflight: 0.05 mm; 95% CI, 0.07-0.03 mm; P < .001). This study found that spaceflight-associated peripapillary optic disc edema and choroid thickening were observed bilaterally and occurred in both sexes. In addition, this study documented substantial peripapillary choroid thickening during spaceflight, which has never been reported in a prospective study cohort population and which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. Data collection on spaceflight missions longer than 6 months will help determine whether the duration of the mission is associated with exacerbating these observed changes in ocular structure or visual function.

Jumping at a chance to control cerebral blood flow in astronauts.

PurposeTo present a systematic review of the current body of literature surrounding spaceflight associated neuro-ocular syndrome (SANS) and highlight priorities for future research.MethodsThree major biomedical databases were searched with the following terms: ((neuro ocular) OR ((brain) AND (eye))) AND ((spaceflight) OR (astronaut) OR (microgravity)) AND (ENGLISH[Language]). Once duplicates were removed, 283 papers were left. Articles were excluded if they were not written in English or conference abstracts only. We avoided including review papers which did not provide any new information; however, two reviews on the pathophysiology of SANS were included for completeness. No limitations on date of publication were used. All included entries were then summarized for their contribution to knowledge about SANS.ResultsFour main themes among the publications emerged: papers defining the clinical entity of SANS, its pathophysiology, technology used to study SANS, and publications on possible prevention of SANS. The key clinical features of SANS include optic nerve head elevation, hyperopic shifts, globe flattening, choroidal folds, and increased cerebrospinal fluid (CSF) volume in optic nerve sheaths. Two main hypotheses are proposed for the pathophysiology of SANS. The first being elevated intracranial pressure and the second compartmentalization of CSF to the globe. These hypotheses are not mutually exclusive, and our understanding of the pathophysiology of SANS is still evolving. The use of optical coherence tomography (OCT) has greatly furthered our knowledge about SANS, and with the deployment of OCT to the International Space Station, we now have ability to collect intraflight data. No effective prevention for SANS has been found, although fortunately, even with persistent anatomic and physiologic neuro-ocular changes, any functional impact has been correctable with spectacles.ConclusionThis is the first systematic review of SANS. Despite the limitations of studying a syndrome that can only occur in a small, discrete population, we present a thorough overview of the literature surrounding SANS and several key areas important for future research are identified.

Objective: To assess the impact of microgravity exposure on ocular rigidity (OR), intraocular pressure (IOP), and ocular pulse amplitude (OPA) following long-term space missions. OR was evaluated using optical coherence tomography (OCT) and deep learning-based choroid segmentation. IOP and OPA were measured with the PASCAL Dynamic Contour Tonometer (DCT). Results: The study included 26 eyes from 13 crew members who spent 157 to 186 days on the International Space Station. Post-mission results showed a 25% decrease in OPA (p < 0.005), an 11% decrease in IOP from 16.0 mmHg to 14.2 mmHg (p = 0.04), and a 33% reduction in OR (p = 0.04). No significant differences were observed between novice and experienced astronauts. Conclusions: These findings reveal previously unknown effects of microgravity on the eye's mechanical properties, contributing to a deeper understanding of Spaceflight-Associated Neuro-ocular Syndrome (SANS). Long-term space missions significantly alter ocular biomechanics and have the potential to become biomarkers of disease progression.

ABSTRACTComputed perimetry remains the gold standard of visual field measurement among glaucoma patients. However, several emerging technologies, made possible by advances in computer programming, smartphone, tablet, or virtual reality, allow alternative means of visual function assessment. These new visual tests may one day have a useful complementary role in visual field testing and to bridge the gap between perimetry and daily experience. Many of these emerging technologies have distinct practical advantages over Ganzfield bowl-based computed perimetry. This paper outlines a discussion of some of these emerging techniques in visual function assessment in glaucoma.How to cite this articleSkalicky SE, Kong GYX. Novel Means of Clinical Visual Function Testing among Glaucoma Patients, Including Virtual Reality. J Curr Glaucoma Pract 2019;13(3):83–87.

Spaceflight associated neuro-ocular syndrome (SANS) is a mission-critical limitation of long-duration spaceflight. The syndrome is comprised of globe flattening, hyperopic shifts, chorioretinal folds, optic disc edema, and cotton-wool spots; however, not every astronaut develops this pathology. Here, we present a hypothesis regarding one potential mechanism, intraocular pressure fluctuations, for the pathophysiology of the development of SANS. Further, we suggest ways in which this mechanism can be tested terrestrially.

Background: Effects of pressure changes especially by long term stay in high altitude area are well known but effect of high atmospheric pressure on ocular tissue is not studied in detail. This study intends to find out the effect of long term exposure to high pressure due to diving on certain parameters of ocular functions Material and Methods: Single centre study performed during 2010–11, for a group of retired naval divers (actively diving) (52 eyes) and a control group of non-divers (retired surface naval personal) (52 eyes). Both groups were matched for age, sex baseline visual status and various parameter related to diving and their detailed ophthalmologic examination was carried out which consisted of testing of visual acuity, IOP, contrast sensitivity, color vision and visual fields. Results: Mean IOP was higher in the diver group (Diver group: 17.04 mm Hg, Control group: 14.81 mm Hg,p > 0.05) and it was statistically significant. There was a high frequency of red-green axis color vision defects (30.7 %) in the diver group. Visual field assessment also showed some difference in both groups but no conclusive pattern could be determined. No significant difference in visual acuity and contrast sensitivity were found between the two groups. Conclusions: There is a definite effect of long term diving on ocular tissue and visual functions. Mean IOP was found high in the diving group and color vision defects were also found more commonly in divers group though no significant difference in visual acuity and contrast sensitivity was found between the two groups.

IntroductionOne of the primary health concerns faced by NASA astronauts on board the International Space Station is a decline in visual acuity. It is believed that increases in intracranial pressure (ICP) due to resistive exercise performed on the station's Advanced Resistive Exercise Device (ARED) may contribute to Spaceflight Associated Neuro‐Ocular Syndrome (SANS), also referred to as the Visual Impairment and Intracranial Pressure (VIIP) syndrome. In a manner similar to low level Valsalva exertion, it is hypothesized that ICP would increase during low level resistance exercise.MethodsSix healthy subjects (4 male, 2 female, age: 27 ± 10 years, weight: 77 ± 15 kg) were recruited to perform low‐level resistance exercises in both the seated and supine positions. A Cerebral Cochlear Fluid Pressure analyzer (CCFP) was used to noninvasively measure ICP by assessing tympanic membrane displacement (Vm) in the inner ear following an auditory stimulus. Increased values of Vm correspond to a decrease in ICP. After a 10‐minute acclimation period, a baseline measurement was taken with the subject at rest in the seated position. ICP was then measured during randomized, isometric, overhead shoulder holds with weights of 0lbs, 2lbs, and 5lbs (per hand). This procedure was then repeated in the supine position. ICP was also measured in the 15‐degree head down tilt (HDT) position following a 10‐minute acclimation period. Significant differences between groups were determined at p&lt;0.05 using a Student's T‐test.ResultsThe relative changes in Vm with increased loading by position are shown in Figure 1. Vm decreased by 40% ± 15% (p=0.001) in the HDT position as compared to the supine baseline, showing a predicted, reliable increase in ICP for positional changes. In the seated position, displacement increased slightly from baseline (12% ± 63%, p=0.412) for all subjects across all weight levels, indicating a statistically nonsignificant decrease in ICP. Measurements in the supine position were more consistent, with decreasing Vm (3% ± 3%, p=0.563) for all subjects across all weight levels, indicating a nonsignificant increase in ICP.DiscussionContrary to our hypothesis, measured data showed no significant change in ICP during low level resistance exercise in either the seated or supine positions. Based on these results, resistance exercise may not be the primary contributing factor to the development of SANS in astronauts. This study will form the basis of future investigation into the effects of exercise and ICP in different such as gender, age, and clinical populations. Sensitivity of the CCFP to motion and pulse artifacts will also be addressed to reduce variability between subjects.Support or Funding InformationSupported by NASA grant NNX13AJ12GThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Astronauts routinely perform submaximal graded exercise testing using cycle ergometry before and during International Space Station (ISS) missions. Aerobic capacity has been estimated from linear extrapolation of heart rate (HR) response and submaximal oxygen consumption (VO2). The elevated HR response to standardized exercise work rates during ISS flight typically has been interpreted as aerobic deconditioning. However, until recently VO2 has not been measured during these tests. PURPOSE: To determine if submaximal VO2 and HR measured during exercise tests on the ISS differ from preflight values as a function of time on board and of exercise intensity. METHODS: Astronauts (n=7) performed exercise tests before flight on a standard cycle ergometer and during flight on the ISS cycle ergometer. In-flight exercise tests were conducted at intervals between days 21 and 149 of the missions. The protocol for submaximal exercise tests consisted of three 5-minute stages at work rates prescribed to elicit 25, 50, and 75% of preflight peak VO2. HR was obtained from ECG and VO2 from metabolic gas analysis. Mixed modeling was used to examine the mean differences between preflight and in-flight measurements of VO2 and of HR over time and at each work rate. RESULTS: During flight, VO2 was significantly lower during the 25% and higher during the 75% exercise stages but did not differ from preflight VO2 at the 50% stage. These differences were consistent across in-flight time points. HR was unchanged from preflight HR at the 25% stage of exercise, although the HR at this stage tended to lower as flight duration increased. At the 50% and 75% stages, HR was elevated early during the missions but did not differ from preflight values later during flight. CONCLUSIONS: The preflight relationship between VO2 and work rate is not maintained during flight, perhaps because of microgravity and/or differences between the ergometers. The changing HR responses across mission duration, some of which do not parallel the VO2 findings, may indicate an acute adaptation early during flight that normalizes later during the missions, and/or an exercise training effect during flight. Thus, estimating aerobic capacity during flight by using only HR responses to submaximal work rates may result in erroneous conclusions. Supported by NASA Contract NAS 9-02078

Microgravity (µG) experienced during space flights promotes adaptation in several astronauts’ organs and tissues, with skeletal muscles being the most affected. In response to reduced gravitational loading, muscles (especially, lower limb and antigravity muscles) undergo progressive mass loss and alteration in metabolism, myofiber size, and composition. Skeletal muscle precursor cells (MPCs), also known as satellite cells, are responsible for the growth and maintenance of muscle mass in adult life as well as for muscle regeneration following damage and may have a major role in µG-induced muscle wasting. Despite the great relevance for astronaut health, very few data are available about the effects of real µG on human muscles. Based on the MyoGravity project, this study aimed to analyze: (i) the cellular and transcriptional alterations induced by real µG in human MPCs (huMPCs) and (ii) the response of human skeletal muscle to normal gravitational loading after prolonged exposure to µG. We evaluated the transcriptomic changes induced by µG on board the International Space Station (ISS) in differentiating huMPCs isolated from Vastus lateralis muscle biopsies of a pre-flight astronaut and an age- and sex-matched volunteer, in comparison with the same cells cultured on the ground in standard gravity (1×g) conditions. We found that huMPCs differentiated under real µG conditions showed: (i) upregulation of genes related to cell adhesion, plasma membrane components, and ion transport; (ii) strong downregulation of genes related to the muscle contraction machinery and sarcomere organization; and (iii) downregulation of muscle-specific microRNAs (myomiRs). Moreover, we had the unique opportunity to analyze huMPCs and skeletal muscle tissue of the same astronaut before and 30 h after a long-duration space flight on board the ISS. Prolonged exposure to real µG strongly affected the biology and functionality of the astronaut’s satellite cells, which showed a dramatic reduction of responsiveness to activating stimuli and proliferation rate, morphological changes, and almost inability to fuse into myotubes. RNA-Seq analysis of post- vs. pre-flight muscle tissue showed that genes involved in muscle structure and remodeling are promptly activated after landing following a long-duration space mission. Conversely, genes involved in the myelination process or synapse and neuromuscular junction organization appeared downregulated. Although we have investigated only one astronaut, these results point to a prompt readaptation of the skeletal muscle mechanical components to the normal gravitational loading, but the inability to rapidly recover the physiological muscle myelination/innervation pattern after landing from a long-duration space flight. Together with the persistent functional deficit observed in the astronaut’s satellite cells after prolonged exposure to real µG, these results lead us to hypothesize that a condition of inefficient regeneration is likely to occur in the muscles of post-flight astronauts following damage.

Partial or total unilateral vestibular loss is the third most common cause of peripheral vestibular dysfunction. Dysfunction of one or both of the vestibular mechanisms can manifest physically as abnormalities of posture, balance, and/or visual acuity. This case report describes physical therapy examination and individualized intervention with vestibular rehabilitation for a patient with unilateral vestibular hypofunction. The patient was an 80-year-old male with electronystamographically confirmed unilateral vestibular loss of 98.3%. He demonstrated altered balance and gaze stability classifying him as having an increased risk for falling. After 5 weeks of individualized vestibular rehabilitation, the patient significantly decreased his fall risk from 11 to 20 of 24 on the Dynamic Gait Index. His gaze stability also improved from a 4 to 1 line disparity with dynamic visual acuity testing. The patient also had a decrease in perceived disability on the Dizziness Handicap Inventory from 30/100 at evaluation to 12/100 at discharge. Individualized vestibular rehabilitation decreased fall risk and improved gaze stability for a patient with significant unilateral vestibular hypofunction.