Human space exploration presents an unparalleled opportunity to study life in extreme environments—but it also exposes astronauts to physiological stressors that jeopardize key systems like vision. Corneal health, essential for maintaining precise visual acuity, is threatened by microgravity-induced fluid shifts, cosmic radiation, and the confined nature of spacecraft living environments. These conditions elevate the risk of corneal abrasions, infections, and structural damage. In addition, Spaceflight-Associated Neuro-Ocular Syndrome (SANS)—while primarily affecting the posterior segment—has also been potentially linked to anterior segment alterations such as corneal edema and tear film instability. This review examines these ocular challenges and assesses current mitigation strategies. Traditional approaches, such as terrestrial eye banking and corneal transplantation, are impractical for spaceflight due to the limited viability of preserved tissues, surgical complexities, anesthetic risks, infection potential, and logistical constraints. The paper explores emerging technologies like 3D bioprinting and stem cell-based tissue engineering, which offer promising solutions by enabling the on-demand production of personalized corneal constructs. Complementary advancements, including adaptive protective eyewear, bioengineered tear substitutes, telemedicine, and AI-driven diagnostic tools, also show potential in autonomously managing ocular health during long-duration missions. By addressing the complex interplay of environmental stressors and biological vulnerabilities, these innovations not only safeguard astronaut vision and mission performance but also catalyze new pathways for regenerative medicine on Earth. The evolution of space-based ophthalmic care underscores the dual impact of space medicine investments across planetary exploration and terrestrial health systems.

Oculomics is an emerging field that leverages ophthalmic imaging data to identify biomarkers of systemic disease, facilitating early diagnosis and risk stratification. Despite its growing recognition, gaps remain in the literature regarding the clinical applications of oculomics. Various systemic diseases—including metabolic disorders (e.g., diabetes mellitus), infectious diseases (e.g., COVID-19), neurodegenerative diseases (e.g., dementia), hematologic disorders (e.g., thalassemia), autoimmune conditions (e.g., rheumatoid arthritis), and genetic syndromes (e.g., Fabry disease)—exhibit ocular manifestations detectable through in vivo confocal microscopy and anterior segment optical coherence tomography, among other imaging modalities. Increasing evidence supports the role of corneal imaging in identifying systemic disease biomarkers, a process further enhanced by artificial intelligence-driven analyses. This review synthesizes the current findings on corneal biomarkers of systemic disease, their ophthalmic imaging correlates, and the expanding role of corneal oculomics in translational medicine. Additionally, we explore future directions for integrating oculomics into clinical practice and biomedical research.

Long-term spaceflight induces multisystem stress, including cardiovascular deconditioning, skeletal muscle atrophy, immune suppression, and neuro-ocular syndromes. Current countermeasures reduce symptoms but cannot replicate the synergistic resilience needed for extended missions or critical illness. Hibernating animals, specifically brown bears (Ursus arctos), survive prolonged immobility, starvation, and bradycardia without resultant pathology. This review incorporates adaptations observed in bears and certain torpid species, including reversible insulin resistance, suppression of muscle atrophy genes MuRF1 and Atrogin-1, and maintenance of the heart despite seasonal production decline. The thirteen-lined ground squirrels (Ictidomys tridecemlineatus) maintain retinal structure and synaptic stability throughout torpor, avoiding neuro-ocular complications despite prolonged inactivity. Mechanisms span from RBM3-dependent synaptic maintenance, titin isoform remodeling under the control of RBM20, mTOR and FOXO pathway regulation, remodeled hydrogen sulfide metabolism, and microbiome-mediated nitrogen salvage. These adaptations are different from human adaptation to microgravity and disuse and offer translational candidates for synthetic torpor, probiotic engineering, neuroprotection, and protein-sparing therapy. Hibernators are not passive stress subjects; they perform coordinated anticipatory responses in multiple organs. Comparing these systems in large and small hibernators, we aim to uncover a biologically realistic path to human resilience. These findings guide a shift from reactive, pharmacological measures for preserving human health during space flight, intensive care, and extreme environments towards proactive, biologically initiated measures.

Many fundamental cellular and molecular changes are known to occur in biological systems during spaceflight, including oxidative stress, DNA damage, mitochondrial damage, epigenetic factors, telomere lengthening, and microbial shifts. We can apply the consequences of these molecular changes in ocular cells, such as the retinal ganglion cells and corneal epithelium, to identify ophthalmologic risks during spaceflight. This review aims to discuss the potential molecular changes in greater detail and apply the principles to ocular cells and ophthalmic disease risk in astronauts. A targeted, relevant search of the literature on the topic and related topics of ocular surface and spaceflight was conducted with scholarly databases PubMed, Web of Science, and Embase from inception to July2024 with search terms "oxidative stress"; "DNA damage"; "Mitochondrial Dysfunction"; "Epigenetics"; "Telomeres"; "Microbiome"; "ocular cells"; "spaceflight"; "microgravity"; "radiation." A total of 115 articles were included following screening and eligibility assessment. Key findings include molecular changes and their contributions to ophthalmic diseases like cataracts, spaceflight-associated neuro-ocular syndrome, and dry eye syndrome. This review provides a comprehensive overview of risks to vision associated with long-duration spaceflight missions beyond low Earth orbit (LEO). Further investigation into targeted countermeasures is imperative to mitigate vision-threatening sequelae in astronauts undertaking deep-space exploration.