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.

In light of the potential effects of spaceflight on the anterior segment of the eye, there is a pressing need for anterior segment imaging to be available and accessible to monitor astronauts’ ocular health, including alterations to the cornea and lens. We aim to highlight the clinical basis and need for anterior segment imaging for astronauts. We explore the impacts of spaceflight-associated hazards, including microgravity and radiation, on astronauts’ risk of developing anterior segment pathology including risk of ocular trauma, infection, dry eye symptoms, cataracts, and possibly additional pathologies from increased radiation exposure. Such risks highlight the potential value that longitudinal assessment of anterior ocular structures would offer in future spaceflight missions. Specifically, anterior segment imaging would enable evaluations of corneal morphology, including longitudinal monitoring for microgravity-induced changes, and evaluation of interventions that aim to preserve anterior segment health during spaceflight. Lastly, non-invasive anterior segment imaging allows for unique insights into astronaut ocular health and can be performed routinely through modalities such as anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM). We discuss these modalities and their implications for astronaut health during future spaceflight.