ALBERT

Description: Enhanced screening for the Visual Impairment/Intracranial Pressure (VIIP) syndrome has been implemented to better characterize the ocular and vision changes observed in some long-duration crewmembers. This includes implementation of in-flight ultrasound in 2010 and optical coherence tomography (OCT) in 2013. Potential risk factors for VIIP include cardiovascular health, diet, anatomical and genetic factors, and environmental conditions. Carbon dioxide (CO2), a potent vasodilator, is chronically elevated on the International Space Station (ISS) relative to ambient levels on Earth, and is a plausible risk factor for VIIP. In an effort to understand the possible associations between CO2 and VIIP, this study explores the relationship of ambient CO2 levels on ISS compared to inflight ultrasound and OCT measures of the eye obtained from ISS crewmembers. CO2 measurements were aggregated from Operational Data Reduction Complex and Node 3 major constituent analyzers (MCAs) on ISS or from sensors located in the European Columbus module, as available. CO2 levels in the periods between each ultrasound and OCT session are summarized using timeseries metrics, including time-weighted means and variances. Partial least squares regression analyses are used to quantify the complex relationship between specific ultrasound and OCT measures and the CO2 metrics simulataneously. These analyses will enhance our understanding of the possible associations between CO2 levels and structural changes to the eye which will in turn inform future analysis of inflight VIIP data.

Description: Research by NASA [1] established that significant risks for visual and ocular impairments associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. It is well established in physiology and pathology that a fundamental role of the microvasculature is to mediate fluid transfers and remodel actively in response to environmental, immune and other stresses. We therefore hypothesize that remodeling of retinal blood vessels necessarily occurs during accommodation of microgravity-induced fluid shifts prior to subsequent development of visual and ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASA's innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) U.S. crew members before and after ISS missions, and (2) head-down tilt in human subjects before and after 70 days of bed rest. We anticipate that results of the two studies will be complete by the Investigators Workshop (January 22, 2017). METHODS: For the 2013 NASA NRA award, we are concluding the analysis of 30 degree infrared (IR) Heidelberg Spectralis images of retinal blood vessels by VESGEN (patents pending), a mature, automated software developed as a translational and basic vascular research discovery tool, particularly for retinal vascular disease. Subjects of our retrospective study include eight ISS crew members monitored for routine occupational surveillance pre- and post-flight, who provided their study consents to NASAs Lifetime Surveillance of Astronaut Health (LSAH) in coordination with approval of the VESGEN retrospective study protocol by NASAs Institutional Review Board (IRB). The ophthalmic retinal images (average image resolution, approximately 5.6 microns per pixel) are blinded as to pre and post ISS status until the second portion of our study, when VESGEN results will be correlated with other ophthalmic and medical findings for the crew members. Due to image resolution challenges, a novel Matlab tool was developed for aligning pre and post images, and comparing (querying) the two images for differences in the morphology of small vessels. RESULTS: During the past year, LSAH approved the release of all astronaut retinal images to our study for VESGEN analysis. Substantial progress on the initial blinded portion of the study is in place. We anticipate that VESGEN analysis of the 32 Spectralis IR retinal images will be complete for presentation at the 2017 IWS meeting. CONCLUSIONS: Modified retinal vascular patterning may offer early-stage predictions of ocular changes resulting in decreased visual acuity for the VIIP syndrome. Novel insights provided by VESGEN into progressively pathological and blinding vascular remodeling in the human retina currently help to guide other NIH- and NASA-supported therapeutic studies of retinal disease and modeling of the VIIP risk. Results of our vascular investigation of the retinas of astronauts pre- and post-flight may help advance the understanding of both healthy and pathological adaptations to fluid shifts in microgravity associated with the VIIP syndrome. Preliminary results indicate that imaging of higher resolution, such as the new OCT angiography (OCT-A) technology, will be required to determine conclusively the role of the smaller retinal and choroidal vessels in VIIP etiology.

Description: Carbon dioxide (CO2) levels on ISS have typically averaged 2.3 to 5.3mm Hg, with large fluctuations occurring over periods of hours and days. CO2 has effects on cerebral vascular tone, resulting in vasodilation and alteration of cerebral blood flow(CBF). Increased CBF leads to elevated intracranial pressure(ICP), which is a factor leading to visual disturbance, headaches, and other central nervous system symptoms. Ultrasound of the optic nerve provides a surrogate measurement of ICP. Inflight ultrasounds were implemented as an enhanced screening tool for the Visual Impairment/Intracranial Pressure (VIIP) Syndrome. This analysis examines the relationships between ambient CO2 levels on ISS and ultrasound measures of the eye in an effort to understand how CO2 may be associated with VIIP and to inform future analysis of inflight VIIP data. Results as shown in Figure2, there was a large timeframe where CO2 readings were removed due to sensor fault errors(see Limitations), from June 2011 to January 2012. After extensive cleaning of the CO2 data, metrics for all of the data were calculated (Table2). Preliminary analyses showed possible associations between variability measures of CO2 and AP diameter (Figure3),and average CO2 exposure and ONSD(Figure4). Adjustments for multiple comparisons were not made due to the exploratory nature of the analysis.