Photorefractive Keratectomy and Laser-Assisted In Situ Keratomileusis on 6-Month Space Missions.

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.Gibson CR, Mader TH, Lipsky W, Schallhorn SC, Tarver WJ, Suresh R, Hauge TN, Brunstetter TJ. Photorefractive keratectomy and laser-assisted in situ keratomileusis on 6-month space missions. Aerosp Med Hum Perform. 2024; 95(5):278-281.

Spaceflight associated neuro-ocular syndrome (SANS): an update on potential microgravity-based pathophysiology and mitigation development.

Long-duration spaceflight is associated with neurologic and ophthalmic clinical and imaging findings in astronauts termed spaceflight associated neuro-ocular syndrome (SANS). These microgravity-induced findings have been well documented by the National Aeronautics and Space Administration (NASA) and are clearly a potential risk for future human space exploration. The underlying pathogenesis of SANS is not well understood, although multiple hypotheses have emerged. Terrestrial analogues and potential countermeasures have also been studied to further understand and potentially mitigate SANS. In this manuscript, we review the current understanding of SANS, discuss the prevailing hypotheses for pathogenesis, and describe current developments in terrestrial analogues and potential countermeasures for SANS.

Implantable Collamer Lens Use in a Spaceflight Participant During Short Duration Spaceflight.

BACKGROUND: The purpose of this report is to document the first use of a single piece, posterior chamber phakic implantable collamer lens (ICL) with a central port in the right eye (OD) of a spaceflight participant (SFP) during a 12-d Soyuz mission to the International Space Station (ISS). We also briefly document the stability of a pre-existing pachychoroid pigment epitheliopathy (PPE) in the macula of his left eye (OS) during this mission.CASE REPORT: Ocular examination, including refraction, slit lamp examination, macular examination by optical coherence tomography (OCT), and tonometry were performed before and after his mission and he was questioned regarding visual changes during each portion of his flight.DISCUSSION: We documented no change in ICL position during his spaceflight. He reported stable vision during liftoff, entry into microgravity, 12 d on the ISS, descent, and landing. Our results suggest that the modern ICL with a central port is stable, effective, and well tolerated during short duration spaceflight. His PPE also remained stable during this mission as documented by OCT.Gibson CR, Mader TH, Lipsky W, Brown DM, Jennings R, Law J, Sargsyan A, Brunstetter T, Danilichev SN, Maezawa Y. Implantable collamer lens use in a spaceflight participant during short duration spaceflight. Aerosp Med Hum Perform. 2023; 94(1):48-50.

Optic nerve sheath diameter and spaceflight: defining shortcomings and future directions.

Neuro-ocular changes during long-duration space flight are known as spaceflight-associated neuro-ocular syndrome (SANS). The ability to detect, monitor, and prevent SANS is a priority of current space medicine research efforts. Optic nerve sheath diameter (ONSD) measurement has been used both terrestrially and in microgravity as a proxy for measurements of elevated intracranial pressure. ONSD shows promise as a potential method of identifying and quantitating neuro-ocular changes during space flight. This review examines 13 studies measuring ONSD and its relationship to microgravity exposure or ground-based analogs, including head-down tilt, dry immersion, or animal models. The goal of this correspondence is to describe heterogeneity in the use of ONSD in the current SANS literature and make recommendations to reduce heterogeneity in future studies through standardization of imaging modalities, measurement techniques, and other aspects of study design.

Elevated perioptic lipocalin-type prostaglandin D synthase concentration in patients with idiopathic intracranial hypertension.

The pathophysiology of vision loss and loss of visual field in patients with idiopathic intracranial hypertension with papilloedema is not fully understood. Although elevated CSF pressure induces damage to the optic nerve due to stasis of axoplasmic flow, there is no clear relationship between the severity of papilloedema and CSF pressure. Furthermore, there are cases of purely unilateral papilloedema and cases without papilloedema despite significantly elevated intracranial pressure as well as papilloedema that can persist despite a successfully lowered intracranial pressure. We hypothesize that at least in some of such cases, in addition to purely pressure-induced damage to the optic nerve, the biochemical composition of the CSF in the subarachnoid space surrounding the orbital optic nerve may play a role in the pathogenesis of vision loss. In this retrospective study, we report on lipocalin-type prostaglandin D synthase concentrations in the CSF within the perioptic and lumbar subarachnoid space in 14 patients with idiopathic intracranial hypertension (13 females, mean age 45 ± 13 years) with chronic persistent papilloedema resistant to maximum-tolerated medical therapy and visual impairment. CSF was collected from the subarachnoid space of the optic nerve during optic nerve sheath fenestration and from the lumbar subarachnoid space at the time of lumbar puncture. CSF was analysed for lipocalin-type prostaglandin D synthase and the concentrations compared between the two sites using nephelometry. The mean lipocalin-type prostaglandin D synthase concentration in the perioptic subarachnoid space was significantly higher compared with the concentration in the lumbar subarachnoid space (69 ± 51 mg/l without correction of serum contamination and 89 ± 67 mg/l after correction of serum contamination versus 23 ± 8 mg/l; P < 0.0001, Mann-Whitney U-test). These measurements demonstrate a change and imbalance in the biochemical environment of the optic nerve. Its possible effect is discussed.

Does Long-Duration Exposure to Microgravity Lead to Dysregulation of the Brain and Ocular Glymphatic Systems?

Spaceflight-associated neuro-ocular syndrome (SANS) has been well documented in astronauts both during and after long-duration spaceflight and is characterized by the development of optic disc edema, globe flattening, choroidal folds, and hyperopic refractive error shifts. The exact mechanisms underlying these ophthalmic abnormalities remain unclear. New findings regarding spaceflight-associated alterations in cerebrospinal fluid spaces, specifically perivascular spaces, may shed more light on the pathophysiology of SANS. The preliminary results of a recent brain magnetic resonance imaging study show that perivascular spaces enlarge under prolonged microgravity conditions, and that the amount of fluid in perivascular spaces is linked to SANS. The exact pathophysiological mechanisms underlying enlargement of perivascular spaces in space crews are currently unclear. Here, we speculate that the dilation of perivascular spaces observed in long-duration space travelers may result from impaired cerebral venous outflow and compromised cerebrospinal fluid resorption, leading to obstruction of glymphatic perivenous outflow and increased periarterial cerebrospinal fluid inflow, respectively. Further, we provide a possible explanation for how dilated perivascular spaces can be associated with SANS. Given that enlarged perivascular spaces in space crews may be a marker of altered venous hemodynamics and reduced cerebrospinal fluid outflow, at the level of the optic nerve and eye, these disturbances may contribute to SANS. If confirmed by further studies, brain glymphatic dysfunction in space crews could potentially be considered a risk factor for the development of neurodegenerative diseases, such as Alzheimer's disease. Furthermore, long-duration exposure to microgravity might contribute to SANS through dysregulation of the ocular glymphatic system. If prolonged spaceflight exposure causes disruption of the glymphatic systems, this might affect the ability to conduct future exploration missions, for example, to Mars. The considerations outlined in the present paper further stress the crucial need to develop effective long-term countermeasures to mitigate SANS-related physiologic changes during long-duration spaceflight.

Optic Disc Edema in Astronauts from a Choroidal Point of View.

INTRODUCTION: Optic disc edema has been well documented in astronauts both during and after long-duration spaceflight and is hypothesized to largely result from increased pressure within the orbital subarachnoid space brought about by a generalized rise in intracranial pressure or from sequestration of cerebrospinal fluid within the orbital subarachnoid space with locally elevated optic nerve sheath pressure. In addition, a recent prospective study documented substantial spaceflight-associated peripapillary choroidal thickening, which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. In the present article, based on the above, we offer a new perspective on the pathogenesis of microgravity-induced optic disc edema from a choroidal point of view. We propose that prolonged microgravity exposure may result in the transudation of fluid from the choroidal vasculature, which, in turn, may reach the optic nerve head, and ultimately may lead to fluid stasis within the prelaminar region secondary to impaired ocular glymphatic outflow. If confirmed, this viewpoint would shed new light on the development of optic disc edema in astronauts.Wostyn P, Gibson CR, Mader TH. Optic disc edema in astronauts from a choroidal point of view. Aerosp Med Hum Perform. 2022; 93(4):396-398.

The odyssey of the ocular and cerebrospinal fluids during a mission to Mars: the "ocular glymphatic system" under pressure.

A significant proportion of the astronauts who spend extended periods in microgravity develop ophthalmic abnormalities including optic disc edema, globe flattening, chorioretinal folds, and hyperopic refractive error shifts. A constellation of these neuro-ophthalmic findings has been termed "spaceflight-associated neuro-ocular syndrome". Understanding this syndrome is currently a top priority for NASA, especially in view of future long-duration missions (e.g., Mars missions). The recent discovery of an "ocular glymphatic system" can potentially help to unlock mechanisms underlying microgravity-induced optic disc edema. Indeed, a major paradigm shift is currently occurring in our understanding of transport of fluids and solutes through the optic nerve following the recent discovery of an optic nerve glymphatic pathway for influx of cerebrospinal fluid. In addition, the recent identification of an entirely new glymphatic pathway for efflux of ocular fluid may have profound implications for fluid dynamics in the eye. Observations pertaining to this ocular glymphatic pathway provide critical new insights into how intracranial pressure can alter basic fluid transport in the eye. We believe that these novel findings have the potential to be game changers in our understanding of the pathogenesis of optic disc edema in astronauts. In the present review, we integrate these new insights with findings on the intracranial and neuro-ophthalmologic effects of microgravity in one coherent conceptual framework. Further studies in this area of investigation could not only provide exciting new insights into the mechanisms underlying microgravity-induced optic disc edema but also offer opportunities to develop countermeasure strategies.

Changes in the Optic Nerve Head and Choroid Over 1 Year of Spaceflight.

IMPORTANCE: While 6-month data are available regarding spaceflight-associated neuro-ocular syndrome, manned missions for 1 year and beyond are planned, warranting evaluation for spaceflight-associated neuro-ocular syndrome beyond 6 months. OBJECTIVE: To determine if the manifestation of spaceflight-associated neuro-ocular syndrome worsens during International Space Station missions exceeding the present 4- to 6-month duration. DESIGN, SETTING, AND PARTICIPANTS: The One-Year Mission Study used quantitative imaging modalities to investigate changes in ocular structure in 2 crew members who completed a 1-year-long spaceflight mission. This study investigated the ocular structure of crew members before, during, and after their mission on the International Space Station. Two crew members participated in this study from March 2015 to September 2016. Analysis began in March 2015 and ended in May 2020. EXPOSURES: Crew members were tested before, during, and up to 1 year after spaceflight. MAIN OUTCOMES AND MEASURES: This study compares ocular changes (peripapillary retinal edema, axial length, anterior chamber depth, and refraction) in two 1-year spaceflight mission crew members with cohort crew members from a 6-month mission (n = 11). Minimum rim width (the shortest distance between Bruch membrane opening and the internal limiting membrane) and peripapillary total retinal thickness were measured using optical coherence tomography. RESULTS: Both crew members were men. Minimum rim width and total retinal thickness increased in both participants throughout the duration of spaceflight exposure to the maximal observed change from preflight (minimum rim width: participant 1, 561 [+149 from preflight] µm at flight day 270; participant 2, 539 [+56 from preflight] µm at flight day 270; total retinal thickness: participant 1, 547 [+135 from preflight] µm at flight day 90; participant 2, 528 [+45 from preflight] µm at flight day 210). Changes in peripapillary choroid engorgement, axial length, and anterior chamber depth appeared similar between the 1-year mission participants and a 6-month mission cohort. CONCLUSIONS AND RELEVANCE: This report documents the late development of mild optic disc edema in 1 crew member and the progressive development of choroidal folds and optic disc edema in another crew member over the duration of 1 year in low Earth orbit aboard the International Space Station. Previous reports characterized the ocular risk associated with 4 to 6 months of spaceflight. As future spaceflight missions are planned to increase in duration and extend beyond low Earth orbit, further observation of astronaut ocular health on spaceflight missions longer than 6 months in duration may be warranted.

Persistent Globe Flattening in Astronauts following Long-Duration Spaceflight.

Posterior globe flattening has been well-documented in astronauts both during and after long-duration space flight (LDSF) and has been observed as early as 10 days into a mission on the International Space Station. Globe flattening (GF) is thought to be caused by the disc centred anterior forces created by elevated volume and/or pressure within the optic nerve sheath (ONS). This might be the result of increased intracranial pressure, increased intraorbital ONS pressure from compartmentalisation or a combination of these mechanisms. We report posterior GF in three astronauts that has persisted for 7 years or more following their return from LDSFs suggesting that permanent scleral remodelling may have occurred.