The cornea during spaceflight: a frontier in space medicine ophthalmology

Introduction

Human spaceflight, particularly for long-duration missions, poses significant challenges to astronaut health and well-being. Understanding the impact of spaceflight on the human body is paramount to ensuring the success and safety of such endeavours [1, 2]. In addition to the neuro-ophthalmic findings of spaceflight associated neuro-ocular syndrome (SANS), there are also effects on the anterior segment including increased risk for cataract and dry eye symptoms [3, 4]. Among the various ophthalmic systems affected by space travel, the cornea is an area of concern due to its sensitivity to environmental changes in microgravity and direct exposure to the space and spacecraft environment. In vivo studies of mice following spaceflight have shown corneal edema, epithelial thickening, and signs of DNA damage and increased apoptosis [5]. As the optical window to visual sensory information, optimizing human corneal health and minimizing risks is of utmost importance to vision and mission performance. This paper aims to explore the effects of spaceflight on the cornea, elucidating the physiological alterations, potential risks, and implications for future human space exploration endeavours.

Clinical observations of the eye during spaceflight

Spaceflight, characterized by microgravity conditions, induces various physiological adaptations in the human body. SANS and increased risk of cataract development have been well documented [3]. Another finding that has been noted is that over 30% of astronauts on the International Space Station (ISS) have reported clinical symptoms of dry eyes, manifested as irritation or foreign body sensations [3], which may potentially be related to alterations in tear film dynamics and ocular surface characteristics. With the microgravity and radiation environment of spaceflight, these clinical findings highlight the need to further investigate the mechanisms underlying corneal changes in microgravity environments. Understanding the full spectrum of physiological changes in the cornea during spaceflight is essential for developing targeted interventions to mitigate their impact on astronaut visual function and ocular health.

Potential risks to corneal health during spaceflight

The microgravity environment of space poses several risks to corneal health. Fluid shifts secondary to microgravity-related changes in hydrostatic pressure gradients have been linked to the development of oedema and other structural changes in various parts of the body. Evidence for such pathology impacting the cornea was seen in murine histological studies from space-flown mice on the STS-133 shuttle mission (totalling 12 days and 19 hours), who were found to develop oedema (indicated by cytoplasmic clearing with cell enlargement) and thickening of the corneal epithelium (indicated by an increase of more than 5 layers of cells in the epithelium) [5]. Following return to Earth (Return Day 1), these same mice were observed to have corneal bullae with 1+ cell in the anterior chamber, suggesting the presence of concurrent inflammatory reaction also involved [5]. The increased exposure to space radiation may provide yet another mechanism of potential injury to the cornea and its associated ocular surface support structures, as prior in vivo murine studies have reported molecular biomarker signs of corneal DNA damage and apoptosis following spaceflight. Prolonged airborne exposure to elevated levels of carbon dioxide, a known complication of the enclosed microgravity environments within the ISS, also provides a known risk to exacerbation of ocular surface irritation in terrestrial research [6, 7]. Lastly, the confined and controlled habitat of spacecraft increases the risk of microbial contamination, potentially leading to corneal infections and other inflammatory conditions. The complexity of these factors highlights the importance of implementing comprehensive strategies to protect astronaut ocular health during space missions.

Risk of foreign body, infection, and thermal injury in microgravity

Spaceflight presents unique challenges related to foreign body exposure given the weightlessness environment. This microgravity environment can lead to the dispersal of particulate matter within spacecraft, increasing the likelihood of foreign bodies contacting the ocular surface. Foreign bodies on the cornea pose a significant risk of corneal abrasion, inflammation, and potential infection, which can compromise visual function and mission performance [8]. The limited availability of medical resources and the remote nature of space missions further compound the challenges associated with managing corneal foreign bodies in space. Damage to the corneal epithelium also increases the risk for corneal infections [9]. The mechanism for dry eyes in astronauts is not well understood but possible disruption in the tear film may also increase the risk for exacerbated infection [10]. Similarly with the risk of foreign body, with the tight quarters in the microgravity environment, there is also risk of chemical and thermal burns to the cornea. Although these risks may not be extremely high, proactive measures, such as implementing strict hygiene protocols, minimizing particulate contamination within spacecraft, and providing astronauts with appropriate eye protection, are essential for mitigating the risk of ocular foreign bodies during spaceflight.

As we look towards colonization missions to the Moon, environmental risks of foreign body-related corneal injuries must be taken into consideration. Specifically, lunar dust (lunar regolith), poses a unique risk to ocular health due to its propensity to infiltrate spacecraft and spacesuits [11]. To date, in vitro studies showed minimal irritancy potential, and in vivo testing in rabbits with lunar dust 72 hours after exposure did not show corneal abrasions [12]. However, the risk of prolonged contact with lunar dust on longer mission durations and after cumulative exposure remains ill-defined. Thus, it is critical to further study the effects of lunar dust to assess for cornea irritation, abrasions, and potential corneal damage in the prolonged space environment. Strategies to mitigate lunar dust exposure, such as meticulous spacecraft and suit maintenance, as well as the development of robust ocular protection measures, will be imperative to safeguarding astronaut ocular health and comfort during lunar exploration missions.

Risk of space radiation on the cornea

Radiation has been considered one of the most serious risks from the spaceflight environment for the human body [13]. Terrestrial studies have illuminated the intricate mechanisms by which space radiation may impact the cornea and ocular surface structures at the molecular level [14–16]. Ionizing radiation (e.g., galactic cosmic radiation (GCR) and solar particle events (SPE)) encountered in space, can directly interact with cellular DNA, causing strand breaks, base modifications, and other genetic alterations [13, 17, 18]. These DNA damages can initiate a cascade of molecular events, leading to cell cycle arrest, oxidative stress, apoptosis, or mutations if not adequately repaired.

The concepts of DNA damage and oxidative stress are also tightly linked, as space radiation has been associated with increased reactive oxygen species (ROS) generation within cells, leading to oxidative stress [19]. These highly reactive ROS can damage proteins, lipids, and other cellular structures, thus further exacerbating cellular dysfunction and tissue injury [20–22]. In vivo studies of space-flown mice on the STS-133 mission strongly indicated signs of oxidative DNA damage and apoptosis to the cornea following spaceflight [5]. 80HdG is a biomarker of oxidative DNA damage which has been observed in mice corneas exposed to both dryness and radiation [5]. In these mice, 8OHdG was present in the areas of corneal oedema and epithelium thickening, implicating oxidative-stress mediated DNA damage. Molecular analyses performed on the corneas from the spaceflight mouse group were also found to have significantly elevated levels of activated caspase-3 levels (relative to controls), a key mediator of oxidative-stress and/or ischemia-induced apoptosis [5]. Taken together, these risks highlight the importance in further understanding the effects of space radiation on corneal health, given the risks to visual function, mission success, and astronaut safety.

Countermeasures and future directions for imaging the cornea during spaceflight

Efforts to mitigate the adverse effects of spaceflight on corneal health include the development of specialized eyewear and protective measures to shield astronauts from harmful radiation, environmental hazards, and foreign bodies [23]. Topical ophthalmic medications onboard the ISS include topical antibiotics (e.g., erythromycin ointment and moxifloxacin drops) and artificial tears (e.g., carboxymethylcellulose) [19, 20]. There is also the Space Eye-Wash system onboard the ISS which allows for continuous irrigation in the setting of chemical exposures [24]. For pain relief, a variety of medications exist including topical anaesthetics (e.g., Tetracaine), oral pain medications (e.g., Acetaminophen, Ibuprofen, Toradol), and cycloplegics (e.g., Cyclopentolate) [25]. Cyanoacrylate glue is available on the ISS which can possibly be used to temporize small corneal perforations, however, surgical intervention of large corneal wound remains an area of further research [25].

Continued updated protocols regarding these risks and management will be of utmost importance to manage infection in-flight. Implementing multi-faceted strategies including preventive ophthalmic education will be essential for safeguarding astronaut corneal health and ensuring optimal visual function during space missions. Additionally, anterior segment imaging technology such as anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) may be able to further elucidate human corneal changes during short term and long term spaceflight. Studying anterior segment imaging to elucidate the morphologic changes of the human cornea for future spaceflight is an area of ongoing research.

Conclusion

The cornea, as a crucial component of the visual system, plays a critical role in maintaining vision, astronaut safety, and mission performance. Investigating how spaceflight influences the cornea is essential for comprehensively addressing astronaut health concerns during prolonged missions in space. By elucidating the physiological changes and potential risks associated with microgravity exposure, this endeavour contributes to the development of strategies aimed at preserving astronaut ocular health during long-duration space missions.

Competing interests

AGL, MD is on the Editorial Board for Eye and a consultant for the National Aeronautics and Space Administration (NASA) and is a consultant for Amgen (speakers’ bureau), Viridian, Alexion (speakers’ bureau), Stoke, Bristol Myers Squibb, and Astrazeneca.