Association of Long-Duration Spaceflight With Anterior and Posterior Ocular Structure Changes in Astronauts and Their Recovery

Reports show that prolonged exposure to a spaceflight environment produces morphologic and functional ophthalmic changes in astronauts during and after an International Space Station (ISS) mission. However, the underlying mechanisms of these spaceflight-induced changes are currently unknown. The purpose of the present study was to determine the impact of the spaceflight environment on ocular structures by evaluating the thickness of the mouse retina, the retinal pigment epithelium (RPE), the choroid and the sclera layer using micro-CT imaging. Ten-week-old C57BL/6 male mice were housed aboard the ISS for a 35-day mission and then returned to Earth alive for tissue analysis. For comparison, ground control (GC) mice on Earth were maintained in identical environmental conditions and hardware. Ocular tissue samples were collected for micro-CT analysis within 38(±4) hours after splashdown. The images of the cross-section of the retina, the RPE, the choroid, and the sclera layer of the fixed eye was recorded in an axial and sagittal view using a micro-CT imaging acquisition method. The micro-CT analysis showed that the cross-section areas of the retina, RPE, and choroid layer thickness were changed in spaceflight samples compared to GC, with spaceflight samples showing significantly thinner cross-sections and layers compared to controls. The findings from this study indicate that micro-CT evaluation is a sensitive and reliable method to characterize ocular structure changes. These results are expected to improve the understanding of the impact of environmental stress on global ocular structures.

A unique constellation of ocular structural changes and visual anomalies known as Spaceflight Associated Neuro-ocular Syndrome (SANS) affects 70 % of crew members after long-duration spaceflight. Current hypotheses regarding the etiology of SANS discuss cephalad fluid shifts and venous congestion, which are correlated with elevated intra-cranial pressure (ICP) and enlarged perivascular spaces (PVS). These PVS comprise the glymphatic system (GS), a recently discovered network of influx and efflux pathways for cerebrospinal fluid (CSF) and metabolites in the central nervous system (CNS). Both glymphatic clearance and traditionally understood CSF circulation are affected by sleep-wake cycles, displaying a significant increase in fluid flow during sleep. Natural sleep has been associated with a 60 % increase in interstitial space in animal studies, which likely enhances GS exchange and outflow. Corresponding studies in humans using contrast-enhanced MRI associate sleep with greater glymphatic clearance compared to wakefulness. The sleep problems of astronauts during long-duration spaceflight have been well documented, ranging from sleep disruption and decreased quality to insufficient sleep duration. With recent terrestrial studies providing evidence that sleep deprivation impairs molecular clearance from the human brain, it follows that similar glymphatic dysfunction may arise due to these conditions in astronauts. Thus, in addition to impairing crew member work performance on long-duration space missions, sleep deprivation may exert long-term neuro-ocular effects via decreased glymphatic efficiency and clearance. The adverse impact of the resulting cognitive and visual disturbances presents a major future performance risk to astronauts. This work discusses the existing body of literature regarding the connections between circadian disruption and glymphatic disruption as a potential contributing mechanism for the development of SANS. This association should receive focused attention in future research as a potential risk factor for SANS. In addition, interventions that enhance extraterrestrial sleep quality and duration may prove to be practical countermeasures for the prevention of this syndrome.

Re: Stenger et al.: Focus on the optic nerve head in spaceflight-associated neuro-ocular syndrome (Ophthalmology. 2019;126:1604–1606)

The Effect of Microgravity on Ocular Structures and Visual Function: A Review

Spaceflight associated neuro-ocular syndrome (SANS) is one of the potential barriers to human long-duration spaceflight (LDSF), including a manned mission to Mars. While a large barrier, the pathophysiology of SANS is not well understood, and functional and structural findings from SANS continue to be further characterized. Currently on the International Space Station (ISS), scheduled visual assessments are static visual acuity, Amsler grid, and a self-reported survey. Additional visual assessments may help the understanding of this neuro-ophthalmic phenomenon, as well as the effects of spaceflight of overall ocular health. In this paper, a case is made for expanding scheduled visual assessments to include dynamic visual, contrast sensitivity (CS), visual field testing, and virtual reality-based metamorphopsia assessment during spaceflight. These further assessments may play a key role in helping to determine the structural and functional changes associated with SANS, which are crucial to maintain astronaut vision during LDSF, as well as for developing countermeasures. Finally, a brief discussion is provided about current challenges to expanding visual testing during spaceflight and potential solutions to these barriers, specifically head-mounted visual assessment technology.

Analysis of Spaceflight-Associated Biometric and Refractive Changes in Astronauts.

Spaceflight associated neuro-ocular syndrome (SANS) alters the vision of astronauts during long-duration spaceflights. There is controversy regarding SANS being similar to patients with idiopathic intracranial hypertension (IIH). IIH has been shown to be due to an elevation in venous sinus pressure. The literature suggests an increase in jugular vein pressure secondary to a headward shift of fluid occurs in SANS but this may not be enough to significantly alter the intracranial pressure (ICP). The literature regarding cardiac output and cerebral blood flow (CBF) in long-duration spaceflight is contradictory, however, more recent data suggests increased flow. Recent modelling has shown that an increase in CBF can significantly increase sinus pressure. The purpose of the present paper is to review the SANS vascular dynamics literature and through mathematical modelling suggest the possible underlying cause of SANS as an elevation in venous sinus pressure, secondary to the redistribution of fluids towards the head, together with a significant increase in pressure drop across the venous system related to the CBF.

Interesting novel and somewhat perplexing physiologic and pathologic neuro-ocular findings have been documented in astronauts during and after long duration space flight (LDSF). These findings collectively have been termed the "space flight-associated neuro-ocular syndrome" (SANS). The National Aeronautics and Space Administration (NASA) in the United States has meticulously and prospectively documented the clinical, ultrasound, optical coherence tomography imaging, and radiographic findings of SANS including unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts (i.e., cotton wool spots). NASA and collaborating researchers continue to study SANS in preparation for future manned missions to space, including continued trips to the ISS, a return to the moon, or perhaps new voyages to the asteroid belt, or the planet, Mars.

Jumping at a chance to control cerebral blood flow in astronauts.

Purpose. To investigate the prevalence of pseudoexfoliation syndrome (PES) in primary angle-closure glaucoma (PACG) and the nature of changes in ocular structures in process of PES progression to determine the choice of pathogenically oriented treatment.Material and methods. For this investigation 220 Uzbek patients (358 eyes) with hyperopic type of eyes (axial length was 22.8 mm and less) have been selected. The main group included 176 patients (286 eyes) with PACG and different degrees of lens opacity. The comparative group consisted of 44 patients (72 eyes) without PACG and clinical PES symptoms, and with analogous lens opacity. The average age was not statistically significant in both groups and was 58.6±1.2 and 56.4±1.4 years, respectively.All patients underwent complete ophthalmologic examinations. Ultrasound biomicroscopy (UBM) was the basic method of investigation using the model 840 (Zeiss-Humphrey Instruments). The measurements were performed in the superior, lateral, inferior, and medial segments of iridocilliary zone.Results. The UBM method allowed to detect PES symptoms in 64.5% of PACG cases even in absence of clinical PES symptoms. The presence of flakes of pseudoexfoliative material of different echo-density was found on structures of iridocilliary zone with its insufficiency. The pseudoexfoliative flakes were associated with a ciliary zonule fiber weakness. Difference of cilliary zonule fibers length differed by 0.2-0.7mm in various segments of measurement. In these cases an alteration of space correlation between iridocilliary structures took place. The asymmetry of iridocilliary structure parameters and disturbance of their topographic relationships detected by the UBM in PES cases with zonules damage lead to a combination of intraocular blocks in one eye in PACG cases. In segments of cilliary zonule fibers stretching (0.68±0.02mm) the UBM reflected a pattern of segmental relative pupillary block. In opposite segment a sharp reduction of visualized cilliary zonule fibers (0.27±0.02mm) was revealed. The UBM reflected a pattern of plateau iris syndrome. In other situations there was observed a combination the pupillary block and the block induced by the crystalline lens.Conclusion. The results of investigations using the UBM method in Uzbek patients showed that the PES was accompanied with PACG in the absence of clinical signs of disease. The PES was accompanied by alterations of topographic relationships of iridocilliary zonule structures in PACG eyes and promoted in these situations an appearance of intraocular blocks combination: relative pupillary block, block of plateau iris syndrome and crystalline lens block that requires a differentiated approach to the choice of pathogenetic treatment tactics of PACG.

Are observations on ultraviolet (UV)- and visible light-induced ocular changes in animals relevant for human pathology? Different conclusions are drawn by different groups, depending on their perspective: while in the epidemiologist's view the evidence for those lesions is mostly limited or insufficient, laboratory scientists continually extend observations on radiation damage in animals. Consequently, there are diverging views on the necessity and specifications for eye protection. In this review, problems of epidemiological surveys and observations in humans and animal studies are discussed, and natural and artificial protection of the eye is outlined. The human and animal eye has an inherent potential for photochemical lesions due to chromophores including the visual pigments that are present at birth. Lifelong light exposure gives rise to additional absorbing molecules. With decreasing wavelengths of the electromagnetic spectrum the number of absorbing molecules rises; therefore, the likelihood of a photochemical reaction grows. As the spectral energy is augmented, more damage will occur. In our view, the knowledge gained from laboratory studies is a significant component of the total evidence from different fields-epidemiology, clinical observations, model studies and theoretical calculations-that UV radiation and short-wavelength visible light can cause acute and chronic changes in ocular structures. Such changes may comprise irreversible damage. Following recently issued recommendations of the major visual health organizations in the United States, protection against UV and blue light should be incorporated into the spectrum of safety considerations for sunglasses.

Type 1 diabetes (T1D) is one of the most common chronic diseases in young individuals. Diabetic nephropathy, being one of the most dangerous complications of T1D, progresses to end-stage renal disease within 10–15 years in 80%. The simultaneous kidney-pancreas transplant prevents insulin therapy and dialysis, thereby avoiding further progression of complications of diabetes. Normalization of carbohydrate metabolism and resolving of uremia after simultaneous kidney-pancreas transplant are beneficial for ocular structures. This article reviews studies on the pattern of changes in ocular structures in the post-transplant period. The procedure improves peripheral microcirculation of the bulbar conjunctiva and corneal innervation. Most studies demonstrate stabilization and improvement of the course of diabetic retinopathy as illustrated by the reduction in active vascular proliferation, need for retinal laser photocoagulation and vitrectomy. Meanwhile, some studies failed to reveal any differences in the morphological functional status of the retina in the pre- and postoperative periods. An increase in cataract rate among simultaneous kidney-pancreas transplant recipients receiving immunosuppressant therapy remains a challenge. Keywords: type 1 diabetes, kidney transplant, pancreas transplant, simultaneous kidney-pancreas transplant, diabetic retinopathy, diabetic macular edema. For citation: Vorobyeva I.V., Bulava E.V., Moshetova L.K., Pinchuk A.V. Ocular changes after simultaneous kidney-pancreas transplant. Russian Journal of Clinical Ophthalmology. 2022;22(2):132–136 (in Russ.). DOI: 10.32364/2311-7729-2022-22-2-132-136.

Maintaining astronaut health during space travel is paramount for further human exploration of the solar system beyond Earth's orbit. Of concern are potential dysregulations in immunity, which could increase the likelihood of cancer and latent viral reactivation. Natural killer (NK) cells are critical effectors of the innate immune system, and their function and phenotype are important to immunosurveillance of nascent tumors and latent viral infections. We compared changes in NK cell phenotype and function in eight crew members who completed an ~6-mo mission to the International Space Station (ISS) with healthy controls who remained on Earth. Assessments were made before (180 and 60 days before launch), during [flight day + 90 days (FD+90) and 1 day before return (R-1)], and after the mission (at R+0, R+18, R+33, and R+66). These samples, plus an additional in-flight sample (FD+180), were collected from a crew member who spent 340 days (~1 yr) on the ISS. NK cell cytotoxic activity (NKCA) against K562 leukemia targets in vitro was reduced by ~50% at FD+90 in ISS crew but not controls. This decrease was more pronounced in "rookie" compared with "veteran" crew members. The ~1-yr mission crew member did not show declines in NKCA against K562 until late in the mission (R-1 and R+0). NK cell numbers, expression of activating and inhibitory receptors, target cell binding, and expression and degranulation of perforin and granzyme B were unaltered with spaceflight. Similarly, when we exposed an immortalized NK cell line (NK-92) to sera collected at different mission time points (before, during, and after flight), there was no effect on NKCA. This is the first study to report impaired NK cell function during long-duration space travel. Countermeasures may be needed to mitigate immune system impairment in exploration class mission crew during long-duration spaceflight missions. NEW & NOTEWORTHY Immune system impairment may inhibit future human space exploration missions to Mars. Natural killer (NK) cells are key components of immunity and vital for tumor surveillance and the prevention of latent virus reactivation. We report that NK cell function is impaired in astronauts during an ~6-mo orbital space mission compared with preflight levels and ground-based controls. Declines in NK cell function were more marked in first-time "rookie" fliers. Countermeasures are needed to preserve NK cell-mediated immunity during spaceflight.

to the editor: The work presented by Sundblad et al. ([5][1]) is important and is likely to improve present international efforts to develop countermeasures against, for example, cardiovascular deconditioning during spaceflight. However, one aspect that is not addressed to a sufficient extent is the

Objective: To evaluate the effect of long-term application of bimatoprost and latanoprost on the anterior chamber depth of primary open-angle glaucoma patients. Methods: The anterior chamber depth (ACD) and axial length (AL) of patients using prostaglandin analogues for open-angle glaucoma (group I) and an age- and gender-adjusted control group (group II) were measured by ultrasonography. Patients using bimatoprost and those using latanoprost were also compared in terms of ACD and AL. Results: The mean ACD of group I (27 eyes of 27 subjects) was significantly lower than that of group II (30 eyes of 30 subjects) (p = .012). Similarly, the ratio of ACD to AL was significantly lower in group I compared with group II (p = .001). The ACDs of patients using bimatoprost or latanoprost and the control group were not significantly different by Kruskal-Wallis test (p = .056), but the differences of these 3 groups in ACD/AL ratios were significant (p = .004). When the Mann Whitney U test was used for pairwise comparison, there was a significant difference between the control group and the patients using latanoprost or bimatoprost in terms of the ACD/AL ratio (p = .008 for each). There was no difference between the patients using latanoprost and those using bimatoprost in terms of the ACD/AL ratio (p = .4). Conclusion: The ACD of patients on prolonged therapy with prostaglandin analogues seems to be lower than than that of the control group. However, prospective long-term studies on large number of subjects are needed to evaluate the effect of each type of prostaglandin on ocular structures.