Evaluation of Optic Disc Edema in Long-Duration Spaceflight Crewmembers Using Retinal Photography.

BACKGROUND: Long-duration spaceflight crewmembers are at risk for spaceflight-associated neuro-ocular syndrome (SANS). One of the earliest manifestations of SANS is optic disc edema (ODE), which could be missed using the subjective Frisén scale. The primary objective of this study is to determine the inter-rater and intrarater reliability of Frisén grade for SANS-induced ODE among a trained observer cohort. The secondary objective is to propose a standardized evaluation process for SANS-induced ODE across International Space Station Partner Agencies. METHODS: Retrospective, double-blinded diagnostic study. Preflight and postflight fundus photographs were presented to subject matter experts who identified and graded ODE. Pairs of images were also compared side-by-side for disc ranking. Grader concordance was assessed for Frisén grading and disc ranking. RESULTS: Expert graders identified Grade 1 ODE in 17.35% of images from 62 crewmembers (9 female, mean [SD] age, 47.81 [5.19] years). Grades 2 and 3 were identified less than 2% of the time. Concordance in Frisén grades among pairs of graders was 70.99%. Graders identified a difference in preflight and postflight fundus photographs 17.21% of the time when using disc ranking. Pairs of graders had complete concordance in disc ranking 79.79% of the time. Perfect intrarater agreement between Frisén grade and disc ranking occurred 77.7% of the time. CONCLUSIONS: These findings demonstrate intergrader and intragrader variability when using the Frisén scale to identify SANS-induced ODE, which is typically milder in presentation than terrestrial cases of idiopathic intracranial hypertension. It is possible to miss early ODE on fundoscopy alone, making it insufficient as a sole criterion for the diagnosis of SANS. A more sensitive and objective method of surveillance is necessary to monitor international crewmembers for ODE, perhaps using a multimodal approach that includes technology such as optical coherence tomography.

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.

Optical Coherence Tomography Analysis of the Optic Nerve Head and Surrounding Structures in Long-Duration International Space Station Astronauts.

Importance: After long-duration spaceflight, morphological changes in the optic nerve head (ONH) and surrounding tissues have been reported. Objective: To develop methods to quantify ONH and surrounding tissue changes using preflight and postflight optical coherence tomographic scans of the ONH region. Design, Setting, and Participants: Two separate analyses were done on retrospective data, with the first comparing a preflight group with a control group, followed by preflight to postflight analysis. All astronaut data were collected on the same instrument and maintained by the National Aeronautics and Space Administration (NASA) Lifetime Surveillance of Astronaut Health. Control data were all collected at the University of Houston. Participants were 15 astronauts who had previously been on an approximately 6-month long-duration mission and had associated preflight and postflight ONH scans. The control group consisted of 43 individuals with no history of ocular pathology or microgravity exposure. Development of algorithms and data analysis were performed between 2012 and 2015. Main Outcomes and Measures: The optical coherence tomography data were analyzed using custom MATLAB programs (MathWorks) in which the Bruch membrane opening (BMO) was manually delineated and used as a reference for all morphological measures. The retinal pigment epithelium (RPE) position 2 mm from the center of the BMO was used to calculate the BMO height. Global and quadrant total retinal thickness and retinal nerve fiber layer (RNFL) thickness were calculated for elliptical annular regions referenced to the BMO. The standard circumpapillary circular scan was used to quantify RNFL and choroidal thickness. Results: Among 15 astronauts (mean [SD] age at preflight evaluation, 48.7 [4.0] years) in this retrospective study, the BMO was recessed in preflight astronauts compared with healthy controls and deepened after long-duration microgravity exposure (median change, -9.9 µm; 95% CI of difference, -16.3 to 3.7 µm; P = .03). After long-duration missions, there was an increase in total retinal thickness to 1000 µm and RNFL to 500 µm from the BMO. Circumpapillary RNFL thickness increased by a median of 2.9 µm (95% CI of difference, 1.1-4.4 µm; P < .01), and there was no change in choroidal thickness (median change, 9.3 µm; 95% CI of difference, -12.1 to 19.6 µm; P = .66). Conclusions and Relevance: After long-duration microgravity exposure, there are disc edema-like changes in the morphology of the ONH and surrounding tissue. The methods developed to analyze the ONH and surrounding tissue can be useful for assessing longitudinal changes and countermeasures in astronauts, as well as potentially for terrestrial disc edema causes.

Astronaut ophthalmic syndrome.

During and after missions on the International Space Station, some astronauts experience ophthalmic changes, including choroidal folds, optic disc edema, cotton-wool spots, globe flattening, and refraction changes. Astronauts with ophthalmic issues had significantly higher plasma concentrations of metabolites that are associated with the 1-carbon metabolic pathway than those without ophthalmic issues. We hypothesized that genetic differences might explain the metabolite differences. Indeed, genetics and B vitamin status were significant predictors of ophthalmic issues. We now have developed a hypothesis regarding the mechanisms that link 1-carbon pathway genetics and the condition that we suggest calling, "astronaut ophthalmic syndrome." We maintain that this condition is genetically predisposed and is associated with endothelial dysfunction that is induced by oxidative stress. Subsequent edema can hinder cerebrospinal fluid efflux and can lead to locally increased pressures in the subarachnoid space within the orbit, which impinges on the optic nerve and/or eye in affected individuals. Confirming this hypothesis will help characterize the genetics of 1-carbon pathway metabolism, homocysteine, oxidative stress, endothelial dysfunction, and cardiovascular and potentially other diseases.-Zwart, S. R., Gibson, C. R., Gregory, J. F., Mader, T. H., Stover, P. J., Zeisel, S. H., Smith, S. M. Astronaut ophthalmic syndrome.

Genotype, B-vitamin status, and androgens affect spaceflight-induced ophthalmic changes.

Ophthalmic changes have occurred in a subset of astronauts on International Space Station missions. Visual deterioration is considered the greatest human health risk of spaceflight. Affected astronauts exhibit higher concentrations of 1-carbon metabolites (e.g., homocysteine) before flight. We hypothesized that genetic variations in 1-carbon metabolism genes contribute to susceptibility to ophthalmic changes in astronauts. We investigated 5 polymorphisms in the methionine synthase reductase (MTRR), methylenetetrahydrofolate reductase (MTHFR), serine hydroxymethyltransferase (SHMT), and cystathionine ß-synthase (CBS) genes and their association with ophthalmic changes after flight in 49 astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both contributed to the odds of visual disturbances. Preflight dehydroepiandrosterone was positively associated with cotton wool spots, and serum testosterone response during flight was associated with refractive change. Block regression showed that B-vitamin status and genetics were significant predictors of many of the ophthalmic outcomes that we observed. In one example, genetics trended toward improving (P = 0.10) and B-vitamin status significantly improved (P < 0.001) the predictive model for refractive change after flight. We document an association between MTRR 66 and SHMT1 1420 polymorphisms and spaceflight-induced vision changes. This line of research could lead to therapeutic options for both space travelers and terrestrial patients.