INTRODUCTION:Epiphora, or excessive tearing, is a commonly reported symptom among those with dry eyes in the terrestrial environment. It is therefore not surprising that a higher frequency of epiphora was demonstrated among astronauts onboard both Space Transportation Shuttle and International Space Station missions. In this review paper, we discuss the pathophysiology and mechanisms of epiphora and consider the additional risk factors due to the extreme environments of spaceflight, including microgravity and, to a lesser extent, radiation. We also discuss potential strategies to mitigate spaceflight-associated epiphora. METHODS:This review utilized articles related to epiphora and the spaceflight environment from various medical literature databases including Embase, Google Scholar, Web of Science, Grey Literature, PubMed, and reliable secondary sources, such as NASA webpages. RESULTS:Our search strategy resulted in 94 articles, and 67 articles were relevant to our study. DISCUSSION:Spaceflight-associated epiphora has a multifactorial etiology related to both reflex tearing and obstruction of the lacrimal drainage system. Dry eyes are closely associated with epiphora in space as the result of ocular irritation causing reflex tearing. Decreased tear drainage may result from the lack of gravitational assistance and the cephalad fluid shift which may create a functional obstruction of the lacrimal drainage system. While primarily a concern with chronic exposure, radiation may irritate the cornea, cause lacrimal and Meibomian gland atrophy, and disrupt tear film stability. Potential countermeasures include maintaining the tear film, mitigating the cephalad fluid shift, and protecting from radiation. Katsev BD, Lee R, Ong J, Gibson CR, Mader TH, Waisberg E, Lipsky W, Sampige R, Berdahl J. Spaceflight-associated epiphora mechanisms and countermeasures. Aerosp Med Hum Perform. 2026; 97(4):272-278.

Spaceflight acutely but transiently elevates intraocular pressure (IOP), often attributed to cephalad fluid shift and choroidal expansion. We propose that anterior segment mechanics, including lens-iris diaphragm position and conventional outflow loading, may contribute to early IOP changes. Comparing phakic and pseudophakic eyes, paired with anterior segment OCT and complementary imaging aboard the International Space Station, could define mechanisms and inform astronaut screening and ocular risk mitigation.

INTRODUCTION:With increasingly ambitious space ventures, astronauts face numerous hazards, including radiation, isolation, altered gravity fields, and hostile environments. Cataracts pose a significant challenge to astronauts' health and performance, both in space and upon returning to Earth. These concerns intensify with deep space exploration, where exposure to high-energy ionizing radiation in the form of galactic cosmic rays, solar particle events, and heavy ions accelerate cataract development. METHODS:This review synthesizes research from Embase, Google Scholar, Web of Science, Grey Literature, PubMed, and NASA sources on cataracts, radiation, and spaceflight. RESULTS:Of 3308 articles identified, 595 duplicates were removed, 476 met inclusion criteria, and 392 were included in the analysis. DISCUSSION:Radiation-induced cataract pathophysiology consists of ionizing radiation induced oxidative stress, which increases free radicals while depleting glutathione. Glutathione is a key antioxidant that interacts with ascorbic acid to protect the lens. Once glutathione levels are compromised, oxidative damage promotes protein aggregation and opacification of the lens, resulting in cataract formation. Countermeasures include optimizing antioxidant defenses, intraocular lens placement, and implementing operational and biomedical strategies such as radiation shielding and protective eyewear. Understanding and addressing these risks is essential for ensuring astronaut visual health and mission success in prolonged space exploration. Katsev BD, Lee R, Kim JH, Leigh A, Ong J, Waisberg E, Lacy AJ, Mader TH, Gibson CR, Berdahl J, Lee AG. Space radiation effects on the glutathione redox cycle and cataract formation. Aerosp Med Hum Perform. 2026; 97(5):354-361.

Spaceflight associated neuro-ocular syndrome (SANS) is a significant ophthalmic complication observed in astronauts during and after long-duration missions, characterized by optic disc edema, globe flattening, choroidal folds, and hyperopic shifts. Unlike papilledema in terrestrial idiopathic intracranial hypertension, optic disc edema in SANS is often asymmetric. The mechanisms underlying this asymmetry remain poorly understood. In this narrative review, we synthesize and critically interpret existing clinical observations, anatomical studies, neuroimaging findings, and experimental evidence, and propose that uneven ocular venous congestion, arising from microgravity-induced cephalad fluid shifts, pre-existing transverse sinus asymmetry, and orbital venous overload, leads to asymmetric optic disc edema by differentially disrupting anterograde ocular glymphatic transport between the eyes. This mechanistic framework highlights the interplay between venous hemodynamics and ocular glymphatic flow as a key factor in SANS pathophysiology. Targeted in-flight monitoring and ground-based analog studies will be essential to rigorously test this hypothesis. To this end, we outline a feasible experimental approach that prospectively integrates preflight cerebral magnetic resonance venography, providing data on transverse sinus dominance, with serial in-flight ophthalmic imaging on the International Space Station. This combined strategy could directly determine whether dural venous sinus anatomy predisposes to uneven ocular venous congestion and asymmetric optic disc edema in microgravity. Insights gained from this work may guide the development of effective countermeasures against SANS and broaden our understanding of ocular fluid dynamics under conditions of altered venous physiology on Earth.

INTRODUCTION:Spaceflight presents unique challenges to ocular health, as visual disturbances such as dry eye symptoms have been frequently reported by astronauts. Matrix metalloproteinases (MMPs), a family of extracellular matrix-degrading enzymes, are known mediators of ocular surface inflammation and tissue remodeling on Earth, particularly in dry eye disease. This review explores the potential role of MMPs in spaceflight-associated ocular conditions, including spaceflight-associated dry eye syndrome and spaceflight-associated neuro-ocular syndrome. METHODS:We searched literature on topics relating to metallomatrix proteins and spaceflight using databases PubMed, MedLine, Embase, and Central from inception to April 2025. RESULTS:Although there are limited studies on direct measurements of tear MMPs during spaceflight, indirect clinical evidence and analog studies suggest that microgravity, radiation, and systemic inflammation may upregulate MMP expression. This contributes to epithelial barrier disruption and impaired wound healing. Rodent models and simulated microgravity experiments further support the mechanosensitive regulation of MMPs across various tissues. DISCUSSION:Given the safety and accessibility of tear collection, MMPs may be useful biomarkers for assessing ocular and systemic changes in astronauts. Understanding MMP expression and regulation in space may inform preventive strategies to preserve vision during long-duration missions. Stephanian B, Ong J, Lee R, Gibson R, Berdahl J, Waisberg E, Mader TH, Lee AG. Ocular matrix metalloproteinases in spaceflight. Aerosp Med Hum Perform. 2026; 97(1):47-54.

Ocular surface tumors, originating from either the conjunctiva or the cornea, primarily fall into three categories of malignant or premalignant neoplasms: ocular surface squamous neoplasia (OSSN), ocular surface melanocytic tumors, and conjunctival lymphoid tumors. These neoplasms can originate from either the conjunctiva or the cornea. Exposure to space radiation, particularly galactic cosmic rays, and solar particle events, poses a significant threat to astronaut health, including the development of ocular malignancies. As such, the objective of this study was to describe the exposure risk for ocular surface malignancies, current mitigation strategies, and management considerations for a mission to Mars. The current mitigation strategies for space radiation include physical and structural shielding along with dietary interventions. Additionally, management of ocular health during a Mars mission can include holoportation, AI-powered diagnostics, newest in-space surgical technology, optical coherence tomography (OCT), and more. Conclusively, further research and collaboration amongst space and healthcare professionals is necessary to ensure the safety and well-being of astronauts during future space exploration endeavors.

Astronauts can develop a distinct collection of neuro-ophthalmic findings during long duration spaceflight, collectively known as Spaceflight Associated Neuro-ocular Syndrome (SANS). These clinical characteristics include optic disc edema, hyperopic refractive shifts, globe flattening, and chorioretinal folds, which may pose a health risk for future space exploration. Obtaining knowledge of SANS and countermeasures for its prevention is crucial for upcoming crewed space missions and warrants a multidisciplinary approach. This review examines the potential causes and countermeasures of SANS, including space anticipation glasses, lower body negative pressure, venoconstrictive thigh cuffs, impedance threshold devices, translaminar pressure gradient modulation, centrifugation, artificial gravity, pharmaceuticals, and precision nutritional supplementation. This paper highlights future research directions for understanding the genetic, anthropometric, behavioral, and environmental susceptibilities to SANS as well as how to use terrestrial analogs for testing future mitigation strategies.

Importance:Spaceflight-associated neuro-ocular syndrome (SANS) could severely impact astronaut performance during long-duration spaceflight (LDSF). The pathophysiology of SANS remains elusive, and no predictors of SANS have been discovered; reliable prediction may offer novel insight into individual susceptibility and interperson variability for SANS and permit prelaunch preparations for in-flight treatment. Objective:To conduct a preliminary analysis of SANS flight data to determine mission-to-mission trends in SANS diagnosis and optic disc edema (ODE) severity. Design, Setting, and Participants:In this cohort study, ocular testing, including optical coherence tomography (OCT), was completed preflight, during flight, and postflight, then retrospectively analyzed in a unique cohort of US National Aeronautics and Space Administration (NASA) astronauts who completed 2 LDSF missions onboard the International Space Station (ISS) from 2007 to 2024. Data were analyzed from April 2024 to April 2025. Exposure:Weightlessness, with average durations of 6 months for each mission. Main Outcomes and Measures:The primary outcome was SANS or non-SANS diagnosis, determined by OCT-based ODE data (when available after 2013) for each mission. Results:Of 71 NASA astronauts who have participated in ISS LDSF, 16 (22.5%) have completed 2 long-duration missions. Four astronauts (20%) were female, and mean ages of astronauts participating in missions 1 and 2 were 46.1 (4.0) and 53.5 (5.2) years, respectively. For these 16 individuals, a SANS diagnosis or nondiagnosis from prior LDSF predicted SANS diagnosis during subsequent LDSF (sensitivity, 85.7%; 95% CI, 42%-100%; specificity, 100%; 95% CI, 66%-100%; positive predictive value, 100%, 95% CI, 54%-100%; negative predictive value, 90%; 95% CI, 56%-100%; P < .001). A subset of this group (5 participants, 10 eyes) possessed an objective metric of ODE across both missions (ie, change in peripapillary total retinal thickness within 250 µm of Bruch membrane opening [ΔTRT]). For individual eyes, ΔTRT of a prior LDSF mission was highly predictive of ΔTRT for a subsequent LDSF (r = 0.94; P < .001). Conclusions and Relevance:In this cohort study, SANS cases from previous LDSF were highly likely to be diagnosed with SANS in subsequent LDSF missions and vice versa, while SANS ODE severity appeared remarkably similar across LDSF missions for individual eyes. To our knowledge, these findings represent the first and only reliable forecast for SANS, permitting precise in-flight treatment and prevention strategies to be tailored for individual astronauts in subsequent LDSF missions, even before launch.

INTRODUCTION:Novel ocular findings have been identified in spaceflight. We discuss their potential association with Spaceflight Associated Neuro-ocular Syndrome (SANS) and integrate them in a framework that may help explain the pathophysiology. METHODS:We reviewed literature using the Medline/PubMed database starting in October 2020. Search terms included ocular circulation, hyperopia, serous chorioretinopathy, pigment epithelial detachment, choroidal folds, choroidal thickening, pachychoroid disease, optic disc edema, venous overload choroidopathy. No date exclusions were placed on the search. Articles were reviewed for relevance. Articles relevant to the pathophysiology of choroidal thickening and choroidal venous overload as it applies to SANS were included. RESULTS:Terrestrial venous overload choroidopathy is thought to be due to impediment to choroidal venous outflow, resulting in dilation of choroidal veins, increased choroidal thickness, pigment epithelial detachments, and serous detachment of the retina. Serous detachment of the retina, pigment epithelial detachments, choroidal folds, and thickening of the choroid were identified on in-flight optical coherence tomography testing. Postflight findings include these, as well as globe flattening. During spaceflight, there is a cephalad displacement of both blood and cerebrospinal fluid. This may lead to pathological consequences in the eye. Remodeling of the choroidal venous vortex system may result in continuance of pathophysiological findings after return to Earth, suggesting the best strategy is prevention. DISCUSSION:Microgravity induced venous overload of the choroid may play a role in SANS pathophysiology, and a venous overload choroidopathy may help explain several SANS features that remain unexplained by an etiology of elevated intracranial pressure. Mampre D, Spaide R, Mason S, Van Baalen M, Gibson CR, Mader TH, Wostyn P, Briggs J, Brown D, Lee AG, Patel N, Tarver W, Brunstetter T. Spaceflight-Associated Neuro-ocular Syndrome as a potential variant of venous overload choriodopathy. Aerosp Med Hum Perform. 2025; 96(6):496-508.

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.

Extended space missions significantly affect astronaut health, leading to various systemic and ocular conditions. The ocular surface and cardiovascular system are particularly susceptible to the unique environment within the spacecraft. This can often lead to pathologic issues such as radiation-induced accelerated atherosclerosis (RIAA), spaceflight-associated neuro-ocular syndrome (SANS) and spaceflight-associated dry eye syndrome (SADES). While traditional treatments for SADES, such as artificial tears and lubricants, provide short-term relief, they may lose effectiveness during long-duration spaceflight. In this context, nanomedicine offers promising solutions for the controlled and targeted delivery of therapeutics, including drugs and biologics. This review assesses the spectrum of ocular health and cardiovascular changes in astronauts, highlights the limitations of existing therapeutic measures, and explores how nanotechnology-based approaches can overcome these limitations by significantly enhancing drug delivery in microgravity. We further discuss the need for rigorous validation to improve the management of ocular and cardiovascular in future space exploration.

The National Aeronautics and Space Administration (NASA) in the United States has been studying a fascinating and unique constellation of neuro-ophthalmic findings collectively known as Spaceflight Associated Neuro-Ocular Syndrome (SANS). SANS is unique to the space environment of microgravity and produces novel physiological and pathological findings that have no direct terrestrial equivalent. The neuro-ophthalmic phenomenon is a major physiologic barrier to future planetary spaceflight. The underlying pathophysiology of SANS remains ill-defined, but since its initial report in 2011, several hypotheses have been proposed including increased intracranial pressure, cerebral venous congestion and glymphatic stasis, compartmentalization of CSF within the orbital nerve sheath sub-arachnoid space (SAS), upward brain shift, inflammation, disrupted axoplasmic transport, and radiation exposure. These aetiologies may not be mutually exclusive and may be interconnected, leading to an integrative, multifactorial aetiology of SANS. This paper critically analyses the various hypotheses of this neuro-ophthalmic phenomenon and the connections between the physiologic and anatomical evidence-based changes observed in spaceflight and terrestrial analogues. Continued prospective, longitudinal study and development of practical countermeasures for SANS will be necessary for future human spaceflight missions including the mission to Mars.

Long-duration spaceflight missions (including the International Space Station [ISS]) are in one of the most remote and harsh environments humans live and work in. Medical emergencies in space are even more complicated in an already high-risk environment. Despite training, ISS crewmembers face many challenges in diagnosing and managing disease with limited diagnostic capability and equipment on the ISS, restricted medication availability, delayed access to medical professionals; and the latency of space missions. Ocular trauma (e.g., cabin contact with equipment, chemical exposure, and foreign body entry) has been well-documented in previous ISS missions, highlighting the vulnerability of crewmembers' vision. While no serious vision loss has yet occurred, the risk of ocular injuries during future commercial and lunar missions remains significant. We review the utilization of onboard diagnostic tools and potential management modalities with current ISS resources for mitigating long-term effects of ocular trauma in the unique microgravity environment of spaceflight. We aim to assess the overall medical preparedness for future space exploration to ensure the well-being and ocular health of crewmembers during extended missions to the Moon, Mars, and beyond.

Spaceflight presents unique challenges to ocular health which must be addressed when considering future long-term missions to Mars and beyond, specifically with increased risk to the anterior segment of the eye. While the posterior segment has been heavily researched via examinations with Heidelberg's Spectralis Optical Coherence Tomography (OCT)2 Module aboard the International Space Station (ISS), evaluation of the anterior segment is not as extensively performed. Despite the capabilities of the Spectralis, which allows for anterior segment imaging via the Anterior Segment Module (ASM), transforming the OCT into an Anterior Segment OCT (AS-OCT), there is limited information available regarding anterior segment effects due to microgravity and spaceflight. Imaging of the anterior segment allows for high resolution details of structures such as the cornea, anterior chamber angles and depth, iris, and lens that may all become affected due to the unique environment astronauts are exposed to during spaceflight. We advocate for the routine use of AS-OCT in ocular examinations aboard the ISS and during spaceflight, offering valuable insight into ocular changes that occur and to help guide management for various anterior segment pathologies one may face, ultimately benefitting both current and future efforts for space travel.

BACKGROUND: This article documents the stability of photorefractive keratectomy (PRK) and laser -assisted in situ keratomileusis (LASIK) in two astronauts during 6-mo missions to the International Space Station. CASE REPORTS: Ocular examinations including visual acuity, cycloplegic refraction, slit lamp examination, corneal topography, central corneal thickness, optical biometry (axial length/keratometry), applanation tonometry, and dilated fundus examination were performed on each astronaut before and after their missions, and in-flight visual acuity testing was done on flight day 30, 90, and R-30 (30 d before return). They were also questioned regarding visual changes during flight. DISCUSSION: We documented stable vision in both PRK and LASIK astronauts during liftoff, entry into microgravity, 6 mo on the International Space Station, descent, and landing. Our results suggest that both PRK and LASIK are stable and well tolerated during long -duration spaceflight.

We read with great interest the article by Tidwell and colleagues[1][1] entitled "Longitudinal Changes in Cerebral Perfusion, Perivascular Space Volume, and Ventricular Volume in a Healthy Cohort Undergoing a Spaceflight Analog" published recently in the American Journal of Neuroradiology . We

ImportanceUnderstanding potential predisposing factors associated with spaceflight-associated neuro-ocular syndrome (SANS) may influence its management.ObjectiveTo describe a severe case of SANS associated with 2 potentially predisposing factors.Design, Setting, and ParticipantsOcular testing of and blood collections from a female astronaut were completed preflight, inflight, and postflight in the setting of the International Space Station (ISS).ExposureWeightlessness throughout an approximately 6-month ISS mission. Mean carbon dioxide (CO2) partial pressure decreased from 2.6 to 1.3 mm Hg weeks before the astronaut’s flight day (FD) 154 optical coherence tomography (OCT) session. In response to SANS, 4 B-vitamin supplements (vitamin B6, 100 mg; L-methylfolate, 5 mg; vitamin B12, 1000 μg; and riboflavin, 400 mg) were deployed, unpacked on FD153, consumed daily through FD169, and then discontinued due to gastrointestinal discomfort.Main Outcomes and MeasuresRefraction, distance visual acuity (DVA), optic nerve, and macular assessment on OCT.ResultsCycloplegic refraction was −1.00 diopter in both eyes preflight and +0.50 − 0.25 × 015 in the right eye and +1.00 diopter in the left eye 3 days postflight. Uncorrected DVA was 20/30 OU preflight, 20/16 or better by FD90, and 20/15 OU 3 days postflight. Inflight peripapillary total retinal thickness (TRT) peaked between FD84 and FD126 (right eye, 401 μm preflight, 613 μm on FD84; left eye, 404 μm preflight, 636 μm on FD126), then decreased. Peripapillary choroidal folds, quantified by surface roughness, peaked at 12.7 μm in the right eye on FD154 and 15.0 μm in the left eye on FD126, then decreased. Mean choroidal thickness increased throughout the mission. Genetic analyses revealed 2 minor alleles for MTRR 66 and 2 major alleles for SHMT1 1420 (ie, 4 of 4 SANS risk alleles). One-week postflight, lumbar puncture opening pressure was normal, at 19.4 cm H2O.Conclusions and RelevanceTo the authors’ knowledge, no other report of SANS documented as large of a change in peripapillary TRT or hyperopic shift during a mission as in this astronaut, and this was only 1 of 4 astronauts to experience chorioretinal folds approaching the fovea. This case showed substantial inflight improvement greater than the sensitivity of the measure, possibly associated with B-vitamin supplementation and/or reduction in cabin CO2. However, as a single report, such improvement could be coincidental to these interventions, warranting further evaluation.

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.