Safety protocols, precautions, and countermeasures aboard the International Space Station (ISS) to prevent ocular injury.

The International Space Station (ISS) is a $100 billion epicenter of human activity in the vacuum of space, displaying mankind's collective endeavor to explore the cosmic frontier. Even within the marvels of technological sophistication aboard the ISS, the human eye remains a highly vulnerable structure. In the absence of multiple layers of protection and risk assessments, crewmembers would face a substantial increase in vulnerability to ocular injury. Aside from stringent preflight screening criteria for astronauts, the ISS is equipped with ophthalmic medications, environmental control and life support systems (e.g., humidity regulation, carbon dioxide removal, pressurized device regulators), and radiation protection to reduce ocular injury. Moreover, additional countermeasures are currently being developed to mitigate the effects of spaceflight-associated neuro-ocular syndrome (SANS) and lunar dust toxicity for the Artemis Program missions. The success of future endeavors hinges not only on continued technological innovation, but also respecting the intricate interplay between human physiology and the extraterrestrial environments. Establishing habitations on the Moon and Mars, as well as NASA's Gateway Program (humanity's first space station around the Moon), will introduce a new set of challenges, underscoring the necessity for continuous insights into ocular health in space. We discuss the safety protocols, precautions, and countermeasures implemented on the ISS to prevent ocular injury - an aspect often overshadowed by the grandeur of space exploration.

Neurostimulation as a technology countermeasure for dry eye syndrome in astronauts.

Dry eye syndrome (DES) poses a significant challenge for astronauts during space missions, with reports indicating up to 30% of International Space Station (ISS) crew members. The microgravity environment of space alters fluid dynamics, affecting distribution of fluids on the surface of the eye as well as inducing cephalad fluid shifts that can alter tear drainage. Chronic and persistent DES not only impairs visual function, but also compromises the removal of debris, a heightened risk for corneal abrasions in the microgravity environment. Despite the availability of artificial tears on the ISS, the efficacy is challenged by altered fluid dynamics within the bottle and risks of contamination, thereby exacerbating the potential for corneal abrasions. In light of these challenges, there is a pressing need for innovative approaches to address DES in astronauts. Neurostimulation has emerged as a promising technology countermeasure for DES in spaceflight. By leveraging electrical signals to modulate neural function, neurostimulation offers a novel therapeutic avenue for managing DES symptoms. In this paper, we will explore the risk factors and current treatment modalities for DES, highlighting the limitations of existing approaches. Furthermore, we will delve into the novelty and potential of neurostimulation as a countermeasure for DES in future long-duration missions, including those to the Moon and Mars.

Impedance threshold device as a countermeasure for spaceflight associated neuro-ocular syndrome (SANS): Mitigating mechanisms in proposed pathophysiology.

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.

Oculomics analysis in multiple sclerosis: Current ophthalmic clinical and imaging biomarkers.

Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. Early recognition and treatment are important for preventing or minimizing the long-term effects of the disease. Current gold standard modalities of diagnosis (e.g., CSF and MRI) are invasive and expensive in nature, warranting alternative methods of detection and screening. Oculomics, the interdisciplinary combination of ophthalmology, genetics, and bioinformatics to study the molecular basis of eye diseases, has seen rapid development through various technologies that detect structural, functional, and visual changes in the eye. Ophthalmic biomarkers (e.g., tear composition, retinal nerve fibre layer thickness, saccadic eye movements) are emerging as promising tools for evaluating MS progression. The eye's structural and embryological similarity to the brain makes it a potentially suitable assessment of neurological and microvascular changes in CNS. In the advent of more powerful machine learning algorithms, oculomics screening modalities such as optical coherence tomography (OCT), eye tracking, and protein analysis become more effective tools aiding in MS diagnosis. Artificial intelligence can analyse larger and more diverse data sets to potentially discover new parameters of pathology for efficiently diagnosing MS before symptom onset. While there is no known cure for MS, the integration of oculomics with current modalities of diagnosis creates a promising future for developing more sensitive, non-invasive, and cost-effective approaches to MS detection and diagnosis.

"Spaceflight-to-Eye Clinic": Terrestrial advances in ophthalmic healthcare delivery from space-based innovations.

The phrase "Bench-to-Bedside" is a well-known phrase in medicine, highlighting scientific discoveries that directly translate to impacting patient care. Key examples of translational research include identification of key molecular targets in diseases and development of diagnostic laboratory tests for earlier disease detection. Bridging these scientific advances to the bedside/clinic has played a meaningful impact in numerous patient lives. The spaceflight environment poses a unique opportunity to also make this impact; the nature of harsh extraterrestrial conditions and medically austere and remote environments push for cutting-edge technology innovation. Many of these novel technologies built for the spaceflight environment also have numerous benefits for human health on Earth. In this manuscript, we focus on "Spaceflight-to-Eye Clinic" and discuss technologies built for the spaceflight environment that eventually helped to optimize ophthalmic health on Earth (e.g., LADAR for satellite docking now utilized in eye-tracking technology for LASIK). We also discuss current technology research for spaceflight associated neuro-ocular syndrome (SANS) that may also be applied to terrestrial ophthalmic health. Ultimately, various advances made to enable to the future of space exploration have also advanced the ophthalmic health of individuals on Earth.

Retina Oculomics in Neurodegenerative Disease.

Ophthalmic biomarkers have long played a critical role in diagnosing and managing ocular diseases. Oculomics has emerged as a field that utilizes ocular imaging biomarkers to provide insights into systemic diseases. Advances in diagnostic and imaging technologies including electroretinography, optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy, fluorescence lifetime imaging ophthalmoscopy, and OCT angiography have revolutionized the ability to understand systemic diseases and even detect them earlier than clinical manifestations for earlier intervention. With the advent of increasingly large ophthalmic imaging datasets, machine learning models can be integrated into these ocular imaging biomarkers to provide further insights and prognostic predictions of neurodegenerative disease. In this manuscript, we review the use of ophthalmic imaging to provide insights into neurodegenerative diseases including Alzheimer Disease, Parkinson Disease, Amyotrophic Lateral Sclerosis, and Huntington Disease. We discuss recent advances in ophthalmic technology including eye-tracking technology and integration of artificial intelligence techniques to further provide insights into these neurodegenerative diseases. Ultimately, oculomics opens the opportunity to detect and monitor systemic diseases at a higher acuity. Thus, earlier detection of systemic diseases may allow for timely intervention for improving the quality of life in patients with neurodegenerative disease.

Optic disc edema during strict 6° head-down tilt bed rest is related to one-carbon metabolism pathway genetics and optic cup volume.

Some astronauts on International Space Station missions experience neuroophthalmological pathologies as part of spaceflight associated neuro-ocular syndrome (SANS). Strict head-down tilt bed rest (HDTBR) is a spaceflight analog that replicates SANS findings and those who had 3-4 risk alleles (G and C alleles from the methionine synthase reductase [MTRR] A66G and serine hydroxymethyltransferase [SHMT1] C1420T, respectively) as compared to 1-2 risk alleles, had a greater increase in total retinal thickness (TRT). The objective of this study was to identify factors that contribute to the individual variability of the development of SANS in a 60 d HDTBR at the German Aerospace Center's:envihab facility, Cologne Germany. 22 of 24 subjects who participated in the HDTBR study provided blood samples for genetic analysis. Total retinal thickness and optic cup volume were measured before and after bed rest. Subjects with 3-4 versus 0-2 risk alleles had greater ΔTRT during and after bed rest, and the model improved with the addition of baseline optic cup volume. This bed rest study confirms that variants of MTRR and SHMT1 are associated with ocular pathologies. Subjects with more risk alleles had the greatest HDTBR-induced ΔTRT, reaffirming that genetics predispose some individuals to developing SANS. Preflight optic cup volume and genetics better predict ΔTRT than either one alone. Whether nutritional supplements can override the genetic influences on biochemistry, physiology, and pathophysiology remains to be tested. These findings have significant implications for both aerospace and terrestrial medicine.