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NASA NTRS2017

Validation of a Manually Oscillating Chair for In-The-Field Assessment of Dynamic Visual Acuity on Crewmembers Within Hours of Returning From Long-Duration Spaceflight

Long-duration spaceflight results in sensorimotor adaptations, which cause functional deficits during gravitational transitions, such as landing on a planetary surface after long-duration microgravity exposure. Both the vestibular system and the central nervous system are affected by gravitational transitions. These systems are responsible for coordinating head and eye movements via the vestibulo-ocular reflex (VOR) and go through an adaptation period upon exposure to microgravity. Consequently, they must also re-adapt to Earth's gravitational environment upon landing. This re-adaptation causes decrements in gaze control and dynamic visual acuity, with crewmembers reporting oscillopsia and blurred vision caused by retinal slip, or the inability to keep an image focused on their retina. This is thought to drive motion sickness symptoms experienced by most crewmembers following landing. Retinal slip can be estimated by dynamic visual acuity (DVA); visual acuity while in motion. Previously, DVA has been assessed in the laboratory where subjects walked at 6.4 km/hr on a motorized treadmill. Using this method, Peters et al. (2011) found that DVA is worsened in astronauts by an average of 0.75 eye-chart lines one day after landing. However, it is believed that re-adaptation occurs quickly and that DVA might be worse immediately upon re-exposure to a gravitational environment. Since many crewmembers are unable to walk safely upon landing, it was necessary to develop a method for replicating the vertical head movements associated with walking. In addition, the use of a chair to imitate the head displacement caused by walking isolates eye-head interactions without allowing for trunk and lower-body compensation, as seen with treadmill walking (Mulavara & Bloomberg 2003). Therefore, a modality for assessing DVA in the field within a few hours of landing was developed. In this study, we validated the ability of a manually operated oscillating chair to reproduce the oscillatory frequency of walking on a treadmill. Healthy non-astronaut subjects (n=14) participated in one test session and completed three static (seated) and three dynamic (walking/oscillated) visual acuity tests. DVA was assessed using a motorized treadmill, an automated oscillating chair, and a manually operated chair, both developed in the Neuroscience Laboratory at JSC. The automated chair was motor-driven and set to oscillate vertically at 2 Hz with a vertical displacement of +/- 5 cm to simulate vertical translation while walking. The manually operated chair was oscillated vertically by a test operator to the beat of a metronome at 120 beats/min (2 Hz) and a vertical displacement of approximately +/- 5 cm. As the subject was oscillated, they were asked to discern the direction gap of Landolt-C optotypes of varying sizes and verbally reported the direction while an operator recorded their response using a gamepad. Subjects were outfitted with accelerometers (sampling rate = 128 Hz) on their head, trunk and lumbar spine. A fast Fourier transform was performed on the vertical trunk acceleration to compare the peak and spread of the distribution of oscillation frequencies for each oscillating condition. The spread of the frequency distribution for the manual chair was not significantly different from either the treadmill or the automated chair. However, all three conditions had similar non-zero standard error values, suggesting a variance in head movement frequency which may affect DVA. The average oscillation frequency of the manual chair (1.85 Hz) was significantly different (α=0.05) from that of treadmill walking (2.24 Hz), but not significantly different from that of the automated chair (1.85 Hz) and all three conditions had small standard errors (SEM = 0.04, 0.06, and 0.08 Hz for manual, treadmill, and automated respectively). This implies that both chairs oscillate at a frequency below that of treadmill walking, but are comparable to each other and reproducible across sessions. Additionally, DVA scores did not vary significantly across conditions. The smaller spread values of the oscillating chairs' frequencies indicated mitigation of variation induced by locomotor strategies, which enables better examination of the issue of VOR adaptation. Furthermore, due to the deconditioned state of crewmembers in the initial hours after landing, it is easier to transport a manual bouncing chair into the field and safer to perform a vision test while seated in a chair versus walking on a treadmill. Therefore, the manually oscillating chair has been deemed to meet and exceed the DVA testing capabilities previously obtained by treadmill walking.

Kreutzberg, G. A.↗
NASA NTRS2017

VIIP 2017 Clinical Update

INTRODUCTION: NASA's Space Medicine community knowledge regarding the "Vision Impairment Intracranial Pressure", or VIIP.has been evolving over time.. Various measures of occupational health related to this condition had to be determined and then plans/processes put into place. The most robust of these processes were inititated in 2010. This presentation will provide a clinic update of the astronaut occupational health data related to VIIP. METHODS: NASA and its international partners require its astronauts to undergo routine health measures deemed important to monitoring VIIP. The concern is that the spaceflight environment aboard ISS could cause some astronauts to have physiologic changes detrimental to either ongoing mission operations or long-term health related to the ocular system and possibly the CNS. Specific medical tests include but are not limited to brain/orbit MRI (NASA unique protocol), OCT, fundoscopy and ocular ultrasound. Measures are taken prior to spaceflight, in-flight and post-flight. Measures to be reported include incidence of disc edema, globe flattening, choroidal folds, ONSD and change in refractive error. RESULTS: 73 ISS astronauts have been evaluated at least partially for VIIP related measures. Of these individuals, approximately 1 in 7 have experienced disc edema. The prevalence of the other findings is more complicated as the medical testing has changed over time. Overall, 26 separate individuals have experienced at least one of the findings NASA has associated with VIIP Another confounding factor is most of the astronauts have prior spaceflight experience at the time of the "pre-flight" testing. DISCUSSION: In 2010 NASA and its US operating segment (USOS) partners (CSA, ESA and JAXA) began routine occupational monitoring and data collection for most VIIP related changes. Interpretation of that data is extremely challenging for several reasons. For example, the determination of disc edema is the most complete finding as we have had highly qualified optometrists routinely and competently performing post-flight funduscopic exams for the entirety of the ISS program. Yet in 2013 NASA added OCT to our in-flight suite of eye exams. Shortly after routine screening with the OCT, a new term appeared within VIIP vernacular - "subclinical disc edema". OCT has much greater ability to measure change within the retina and provides significantly more data to analyze, understand and communicate out. Communicating VIIP data clearly adds even more challenge. Historically we've reported data per eye and not necessarily per person. This has led to difficulty in understanding how many individuals have experienced "VIIP" within the aerospace medicine community. The presenter will attempt to provide clear and concise communication of VIIP findings.

Tarver, William↗
NASA NTRS2017

Stroboscopic Goggles as a Countermeasure for Dynamic Visual Acuity and Landing Sickness After Long-Duration Spaceflight

Gravity transitions cause changes in the vestibulo-occular reflex (VOR), which manifests as poor gaze control, a decrement in dynamic visual acuity (the ability to maintain gaze while in motion), both of which are caused by retinal slip. Retinal slip, the inability to keep an image focused on the retina, can drive or worsen sensory conflict, resulting in motion sickness (MS). Currently 100% of returning crewmembers report MS symptoms, which might affect their ability to perform mission critical tasks immediately after landing. Reschke et al. (2007) demonstrate that stroboscopic vision goggles improve motion sickness onset and symptom severity in motion sickness driven by retinal slip.

Rosenberg, M. J. F.↗
NASA NTRS2017

Analysis by NASA's VESGEN Software of Retinal Blood Vessels in Human Subjects Undergoing Head-Down Tilt During 70-Day Bed Rest

Significant risks for visual impairment associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions [1]. We hypothesize that microgravity-induced fluid shifts result in pathological changes within blood vessels of the retina that precede development of visual and other ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated for two studies in 30deg infrared (IR) Heidelberg Spectralis(Registered Trademark) images with NASA's innovative VESsel GENeration Analysis (VESGEN) software [2,3]. The retrospective studies include: (1) before, during and after (pre, mid and post) 6º head-down tilt (HDT) in human subjects during 70 days of bed rest, and (2) before and after missions to the International Space Station (ISS) by U.S. crew members. Results for both studies are almost complete. A preliminary example for HDT is described below.

Microgravity↗
NASA NTRS2017

Association Between Vascular Density and Loss of Protective RAS During Early NPDR by Fractal Dimension

Purpose: Our hypothesis predicts that blood vessels within the retina increase in density during early-stage nonproliferative diabetic retinopathy (NPDR), based on previous results of a small retrospective study. For the current prospective study, the remodeling of arteries and veins during progression of early NPDR is assessed by a repertoire of parameters that includes the fractal dimension (D(sub f) ). In complex structures such as branching vascular trees, D(sub f) is a sensitive measure of space-filing capacity. The renin-angiotensin system (RAS) is implicated in DR pathogenesis and the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population instrumental in vascular repair. Methods: Arterial and venous branching patterns were extracted from images of 6 normal controls and 3 early NPDR subjects (2 moderate, 1 mild) acquired by Heidelberg Spectralis (Registered Trademark) OCT following fluorescein angiography (FA). The vascular branching patterns were analyzed by NASAs VESsel GENeration Analysis (VESGEN) software, in which skeletonized representations were generated automatically to yield D(sub f) by the box-counting method. For binary 2D images, D(sub f) varies between limiting Euclidean dimensions of 1 and 2. Peripheral blood of diabetics and controls was collected for CD34+ CAC isolation. The gene expression of RAS in CACs was assessed by qPCR for Mas receptor to Ang-(1-7). The vasoreparative function of the CACs was measured by migration ability toward CXCL12 (SDF-1). Results: By D(sub f), venous and arterial densities were 1.370 +/- 0.006 and 1.329 +/- 0.016 for early NPDR, compared to 1.318 +/- 0.012 and 1.320 +/- 0.036 for control. The space filling capacity in early NPDR measured by D(sub f), a sensitive parameter, therefore demonstrated a pronounced increase for veins, but not for arteries. Mas receptor mRNA in CACs was increased in diabetics without DR but reduced with onset of NPDR, indicating possible loss of compensation of protective RAS during early DR. Migratory dysfunction of CD34+ cells was further associated with DR. Conclusions: As assessed by the fractal dimension in our preliminary study, the space-filling capacity of veins, but not arteries, was greater in early NPDR than in control. Larger patient populations will be examined as we complete our ongoing longitudinal study. Results further suggest the protective RAS axis within diabetic CACs is lost early in DR and is associated with increased vascular remodeling as evidenced by VESGEN analysis.

vascular↗
NASA NTRSDate not supplied

B Complex 5-Methyltetrahydrofolate, Riboflavin, Pyridoxine, and Methylcobalamin Supplementation as a Non-Mechanical Countermeasure to Mitigate Optic Disc Edema Changes During Strict 6º Head-Down Tilt Bed Rest

A subset of astronauts on International Space Station missions have experienced optic disc edema, part of what is characterized as Spaceflight Associated Neuro-ocular Syndrome (SANS). While the precise cause of SANS is unknown, it is likely that there are multiple contributing factors, including genetic and environmental factors. Our recent work has shown that crewmembers with SANS have higher concentrations of metabolic biomarkers of impairments in the one-carbon metabolic pathway compared to unaffected astronauts - before, during, and after f light (1). B-vitamin status and the presence of one-carbon pathway single nucleotide polymorphism (SNP) variants predicted the incidence of SANS pathologies, including optic disc edema (2). Specifically, the G allele of methionine synthase reductase (MTRR) A66G and the C allele of serine hydroxymethyltransferase-1 (SHMT1) C1420T were associated with increased incidence of SANS pathologies (2). In a recent 30-d bed rest head-down tilt study with 0.5% CO2 exposure, 5 of 11 subjects developed optic disc edema (4) and the same SHMT1 C1420T and MTRR A66G genetic variants were associated with a larger increase in total retina thickness, a quantitative measure of optic disc edema (5). We published a multi-hit hypothesis of how genetics represents an indispensable element of SANS, which is a multifactorial problem (6). In brief: endothelial dysfunction secondary to genetic, biochemical/nutritional, and physiological (e.g., cardiovascular/fluid shift) f actors could lead to optic disc edema and the other ocular changes that occur in SANS. We expanded this hypothesis to include the possibility that genetic effects on B-vitamin status can alter nitric oxide synthesis and oxidative stress in the endothelium. This in turn could alter the turnover of structural components of the sclera, making it more susceptible to pathologic changes when faced with stressors related to the unrelenting headward fluid shift that occurs in weightlessness and strict head-down tilt bed rest (5). If the relationships that we have observed in flight and ground-based research hold true for the SANS Countermeasure Study, these genetic factors could predict who will be more susceptible to the development of SANS, and more importantly could also provide countermeasure options. As has been shown extensively in the literature, vitamin supplementation can serve to overcome genetic hindrances to one-carbon biochemistry and vascular physiology. Thus, based on our findings, publications, and hypotheses, supported by extensive supporting literature, we had hoped to test in the SANS Countermeasure Study the efficacy of a bioactive B-vitamin complex as a countermeasure to optimize function of the one-carbon pathway and prevent or mitigate optic disc edema during strict 6-degree head down tilt bed rest, and ultimately in space f light. While the supplement is no longer planned to be tested in the SANS Countermeasure Study because of laws regulating supplementation studies like this costing much more than initially planned, we will assess the contribution of one-carbon pathway genetics and B-vitamin status to SANS risk.

S R Zwart↗
NASA NTRSDate not supplied

Comparison of Multispectral Imaging and Traditional Fundoscopy in the Detection of Terrestrial Retinal and Optic Nerve Pathologies like those Encountered During and/or Immediately Following Long-Duration Spaceflight

INTRODUCTION: The purpose of this investigation was to evaluate if MultiColor Imaging (MCI) can replace color fundus photography (CFP) as a diagnostic screening tool during spaceflight. MCI significantly reduces crew time (approx. 115 minutes/session, 36 hours/year) by eliminating nominal on-orbit fundoscopy sessions, while also providing the option to capture a larger field of view (55 vs. 35). METHODS: A comprehensive PubMed literature search was conducted using the following key words: multicolor, multispectral, imaging, retina, choroid, optic nerve, optic disc, and papilledema. Publications were filtered based on optic nerve and chorioretinal pathologies matching those seen during or immediately after spaceflight: optic disc edema (ODE), cotton wool spots (CWS), retinal hemorrhage, pigment epithelial detachment (PED), and serous chorioretinopathy (SCR). In a separate effort, 44 multicolor images (30 abnormal) of terrestrial patients were graded and compared to corresponding color fundus images acquired at the Doheny Eye Centers and UCLA. RESULTS: The search identified 340 articles; 9 describing MCI in relevant pathologies, 6 comparing MCI to CFP. MCI is superior in detecting CWS (1 paper), PED (2 papers), retinal hemorrhages (2 papers), and choroidal folds (1 paper), and can better delineate extent or boundaries of subretinal fluid and identify areas of RPE damage in SCR (2 papers). On MCI, ODE was described as a hyperreflective ring with a green shift and indistinct disc margins, with equaldetectability as using CFP (3 papers). Grading at Doheny Eye Institute confirmed these findings. DISCUSSION: MCI can effectively detect all retinal and optic nerve findings detectable by CFP during and immediately post-spaceflight and represents a suitable replacement as an on-orbit diagnostic screening tool. Additionally, by eliminating the nominal on-orbit fundoscopy sessions, dozens of crew hours are spared per year by utilizing MCI.

Jorge Nagel↗
NASA NTRSDate not supplied

Correlated Changes in Retinal Thickness and Visuomotor Function in Asymptomatic Plaquenil Toxicity Patients

We have previously shown that a 5-minute eye-movement test can capture a number of largely independent “oculometric” parameters of human visual/visuomotor function (Liston & Stone, 2014). This test has been successfully used to characterize mild neural impairment due to traumatic brain injury, sleep and circadian disruption, and alcohol consumption (Liston et al., 2017; Stone et al, 2019; Tyson et al, 2021). Here, we extend this approach to study patients at risk of progressive posterior-segment illness to see how oculometrics relate to standard clinical ophthalmological measures. Five female patients (<20:40 BCVA, 34-60 years old) undergoing hydroxychloroquine treatment (2-7mg/kg/day for 10-23 years for rheumatologic illness) have participated thus far. Under monocular viewing conditions in randomized order, they tracked a moving spot undergoing radial step-ramp motion in one of 90 randomized directions, at one of 5 randomized speeds, starting at random times (for details, see Stone et al, 2019). We computed nine independent oculometrics (latency, initial acceleration, steady-state gain, proportion smooth, saccadic rate, saccadic amplitude, direction noise, speed responsiveness, and speed noise). Spectral-domain optical coherence tomography (Zeiss, Dublin, CA) was used to measure the average thickness of the nine Early Treatment Diabetic Retinopathy Study macular sectors from the internal limiting membrane to the retinal pigmented epithelium. We used Pearson’s correlation between retinal thickness and our oculometrics with t-statistics to test separate one-sided hypotheses across 10 retinae. Our preliminary analysis found significant changes in several different aspects of visuomotor performance. Most notably, latency increased, initial acceleration decreased, and steady-state pursuit gain decreased as retinal thickness decreased (r2 = 0.364, 0.579, and 0.692; one-tailed P = 0.032, 0.005, and 0.001, respectively). Speed responsiveness appeared to decrease, but this effect was marginal for our current sample (r2 = 0.253, P = 0.069). Lastly, direction discrimination and saccadic behavior appeared unchanged. We conclude that oculometrics may provide sensitive measures of changes in retinal thickness. More importantly, oculometrics have the potential to detect impairment before it becomes evident with standard clinical imaging tools, while also providing insight into the behavioral implications of any resulting deficits in visual/visuomotor function.

eye movements↗
NASA NTRS2022

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

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Interventions or Exposures: Spaceflight and lower-body negative pressure. Main Outcomes and Measures: Changes in minimum rim width, optic cup volume, Bruch membrane opening height, peripapillary total retinal thickness, and macular thickness. Results: 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 mm^3; 95% CI, 0.030-0.046 mm^3; 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. Conclusions and Relevance: 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.

Laura P. Pardon↗
NASA NTRSDate not supplied

An Oculometric Standard to Assess the Performance of the Ocular System for Long Duration Spaceflight

Changes in the human brain, due to spaceflight, have been a challenge to the space program since its inception; a challenge that is becoming more acute as extended International Space Station (ISS) missions become routine, a return to crewed lunar exploration is about to begin, and a multi-year crewed trip to Mars is being planned. Determining the extent to which neurophysiological adaptations may adversely impact performance in operational tasks, assessing the full-time course of these changes, and identifying/mitigating any potential long-term health consequences are crucial steps required to enable safe crew-autonomous, long-duration, deep-space missions. Vision is the predominant perceptual sense used to guide cognition and motor control in humans. Thus, it is critical for the success of any future, long-duration mission to understand how long-term exposure to microgravity and to other stressors of spaceflight and their interactions, impact visual function. This is an especially challenging task given the small and disparate samples from which we have been and will be able to collect human performance data. NASA has recently been carefully tracking spaceflight-induced ophthalmic changes, driven in large part by the fluid shifts related to microgravity. In particular, a recent study of Optical Coherence Tomography (OCT) postflight measures revealed that more than two-thirds of US crew members experience significant increases in retinal thickness after 6month or longer ISS missions. Space Associated Neuro-ocular Syndrome (SANS) also includes visual acuity decrements and other ocular structural changes that could adversely impact in-flight performance as missions become longer. However, the impact of spaceflight on the visual system is not limited to the retina. Recent comparisons of pre-and post-flight brain images have revealed structural changes throughout the brain that implicate visual, visuomotor, and visual-cognitive pathways, consistent with observed functional impacts (e.g., decreased speed/accuracy/timing of fine goal-oriented movements). Current limitations on inflight testing make it very difficult to determine when and under what conditions SANS and other disruptions of human neurological subsystems arise. Currently, one cannot anticipate the time course and extent of impairment and recovery. This study addresses this knowledge gap by creating an integrated framework of the relevant existing literature on visual and oculomotor function during spaceflight with an eye towards complementing current structural measures of visuomotor impairment with new oculometric standard measures. Using eye-movement based visual function assessment and diagnostics would provide a valuable enhancement of crew health and performance monitoring in support of deepspace exploration.

Vision↗
NASA NTRS2022

A Multi-omics Longitudinal Study of the Murine Retinal Response to Chronic Low-dose Irradiation and Simulated Microgravity

The space environment includes unique hazards like radiation and microgravity which can adversely affect biological systems. We assessed a multi-omics NASA GeneLab dataset where mice were hindlimb unloaded and/or gamma irradiated for 21 days followed by retinal analysis at 7 days, 1 month or 4 months post-exposure. We compared time-matched epigenomic and transcriptomic retinal profiles resulting in a total of 4,178 differentially methylated loci or regions, and 457 differentially expressed genes. Highest correlation in methylation difference was seen across different conditions at the same time point. Nucleotide metabolism biological processes were enriched in all groups with activation at 1 month and suppression at 7 days and 4 months. Genes and processes related to Notch and Wnt signaling showed alterations 4 months post-exposure. A total of 23 genes showed significant changes in methylation and expression compared to unexposed controls, including genes involved in retinal function and inflammatory response. This multi-omics analysis interrogates the epigenomic and transcriptomic impacts of radiation and hindlimb unloading on the retina in isolation and in combination and highlights important molecular mechanisms at different post-exposure stages.

Prachi Kothiyal↗
NASA NTRS2022

Optimizing Screening for Preventable Blindness With Head-Mounted Visual Assessment Technology

Age-related macular degeneration (AMD) is a leading cause of blindness and is diagnosed as early-stage or late-stage. Early-stage AMD is usually asymptomatic and entails pigmentary changes of the retina (Ayoub & Patel, 2009). As the disorder progresses, there are atrophic or neovascular changes that distort vision, especially the central visual field (Ayoub & Patel, 2009). There are several genetic and non-genetic risk factors for AMD and no proven therapy to slow or reverse late-stage atrophic AMD, while anti-VEGF has effectively treated late-stage neovascular AMD. Several genes of interest have also been investigated thoroughly thus far in their connection to AMD and the CFH and ARMS2 genes have shown promise in understanding the genetic basis of the disorder (Awh et al., 2013). There are other epigenetic and environmental factors as well including smoking and low antioxidant levels (Cano et al., 2010). Ongoing investigations include antioxidant supplementation and a smoking cessation regimen to reverse early-stage AMD (Cano et al., 2010). Progress in treating AMD as a disorder across its varied stages requires newer therapeutics along with a more detailed understanding of the genetic and cellular pathways of pathophysiology is needed to better counter this prevalent disorder of the eye.

age-related macular degeneration↗
NASA NTRS2024

Oculometric Biomarkers of Visuomotor Deficits in Clinically Asymptomatic Patients With Systemic Lupus Erythematosus Undergoing Long-Term Hydroxychloroquine Treatment

Introduction: This study examines a set of oculomotor measurements, or “oculometric” biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

eye movements↗
NASA NTRSDate not supplied

Extraordinary Accomplishments of the In Space Production Applications Portfolio in 2024

The purpose of the NASA In-Space Production Applications (InSPA) program is to provide funding and expertise to help brilliant United States innovators and businesses traverse the technology “Valley of Death” by proving out their concepts for in-space manufactured materials and products that will ultimately be sold to customers on the Earth. Scientific and technological advances on the International Space Station (ISS) and on Earth coupled with evolving societal needs are collectively enabling InSPA-funded teams to produce data streams and advanced biological, chemical, and physical materials solutions with economic value. We report on an extraordinary year of accomplishments on the ISS and highlight top InSPA and ISS National Lab results that span historic firsts in cancer research, stem cells, crystal production, optical fiber production, drug discovery, in-space treatments with RNA therapeutics, and production of artificial retinas from space. We assert that the results have enormous potential, are transforming the space exploration ecosystem and are the “seeds” of a microgravity industrial revolution that are shaping national microgravity strategy.

in spa↗