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

During long-duration spaceflights, nearly all astronauts exhibit some change in ocular structure within the spectrum of spaceflight-associated neuro-ocular syndrome. To quantitatively determine in a prospective study whether changes in ocular structures hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome occur during 6-month missions on board the International Space Station (ISS). The Ocular Health ISS Study of astronauts is a longitudinal prospective cohort study that uses objective quantitative imaging modalities. The present cohort study investigated the ocular structure of 11 astronauts before, during, and after a 6-month mission on board the ISS. Changes in ocular structure (peripapillary edema, axial length, anterior chamber depth, and refraction) hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome during 6-month missions on board the ISS were assessed. Statistical analyses were conducted from August 2018 to January 2019. Before launch, the 11 astronauts were a mean (SD) age of 45 (5) years, a mean (SD) height of 1.76 (0.05) m, and a mean (SD) weight of 75.3 (7.1) kg. Six astronauts did not have prior spaceflight experience, 3 had completed short-duration missions on board the Space Shuttle, and 2 had previous long-duration spaceflight missions on board the ISS. Their mean (SD) duration on board the ISS in the present study was 170 (19) days. Optic nerve head rim tissue and peripapillary choroidal thickness increased from preflight values during early spaceflight, with maximal change typically near the end of the mission (mean change in optic nerve head rim tissue thickness on flight day 150: 35.7 μm; 95% CI, 28.5-42.9 μm; P < .001; mean choroidal thickness change on flight day 150: 43 μm; 95% CI, 35-46 μm; P < .001). The mean postflight axial length of the eye decreased by 0.08 mm (95% CI, 0.10-0.07 mm; P < .001) compared with preflight measures, and this change persisted through the last examination (1 year after spaceflight: 0.05 mm; 95% CI, 0.07-0.03 mm; P < .001). This study found that spaceflight-associated peripapillary optic disc edema and choroid thickening were observed bilaterally and occurred in both sexes. In addition, this study documented substantial peripapillary choroid thickening during spaceflight, which has never been reported in a prospective study cohort population and which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. Data collection on spaceflight missions longer than 6 months will help determine whether the duration of the mission is associated with exacerbating these observed changes in ocular structure or visual function.

PurposeRecent retrospective clinical studies and animal experiments have suggested that cerebrospinal fluid pressure (CSFP) is important in glaucoma, acting through the translaminar pressure (TLP = IOP − CSFP), which directly affects the optic nerve head. In this study, IOP and intracranial pressure (ICP; a surrogate of CSFP) were measured at various body positions to quantify the determinants of TLP.MethodsWe have developed an implantable wireless pressure telemetry system based on a small piezoelectric sensor with low temporal drift. Telemetry transducers were placed in the anterior chamber to measure IOP and in the brain parenchyma at eye height to measure ICP. IOP was calibrated against anterior cannulation manometry, and ICP/CSFP was calibrated against an intraparenchymal Codman ICP Express microsensor. We measured IOP, ICP, and TLP = IOP − ICP continuously at 200 Hz in three male nonhuman primates (NHPs) in three trials; pressures were then averaged for 30 seconds per body position. Relative change of IOP, ICP, and TLP from the supine (baseline) position to the seated, standing, and inverted positions were quantified.ResultsTLP changed significantly and instantaneously from the supine to seated (+14 mm Hg), supine to standing (+13 mm Hg) and supine to inverted (−12 mm Hg) positions (P < 0.05). There was no significant TLP change for supine to prone. ICP showed greater relative change than IOP.ConclusionsTLP change due to body position change is driven more by ICP/CSFP than IOP. IOP, ICP, and TLP variability, coupled with telemetry, should allow us to test the hypotheses that IOP, ICP, or TLP fluctuations contribute independently to glaucoma onset or progression.

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

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

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.

Previous studies indicate that ocular blood flow is altered in eyes with choroidal melanoma. In the present study pulsatile ocular blood flow (POBF) was assessed to investigate whether there exists a correlation between tumour size and ocular blood flow parameters. Twenty-two patients with unilateral untreated choroidal melanoma were studied using two measurement techniques: POBF was measured with a pneumotonometer and local foveal fundus pulsation amplitude (FPA) by laser interferometry, and results were correlated. Tumour volume was calculated using the ellipsoidal solid model and was correlated to POBF and FPA. Levels of POBF and FPAs tended to be higher in tumour eyes compared with unaffected eyes, but the differences did not reach the level of significance. Both methods showed a high degree of correlation in unaffected eyes. In tumour eyes the correlation was slightly less pronounced. There was no correlation between tumour and POBF or FPA. Our results do not indicate choroidal hyperperfusion in patients with choroidal melanoma. The clinical usefulness of measuring POBF in tumour patients may be limited.

To determine the interdependence of intracranial pressure (ICP) and intraocular pressure (IOP) and how it affects optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left eye, and anterior chamber in the left eye. This allowed ICP, lumbar cistern pressure (LCP), optic nerve subarachnoid space pressure (ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from lowering ICP (via shunting cerebrospinal fluid (CSF) from the ventricle) were recorded. At baseline, all examined pressures were different (ICP<LCP<ONSP), but correlated (P>0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient (TLPG) remained stable (ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as ICP declined (ICP-IOP independent zone). The optic nerve pressure gradient (ONPG) and trans-optic nerve pressure gradient (TOPG) increased linearly as ICP decreased through both the ICP-IOP dependent and independent zones. We conclude that ICP and IOP are coupled in a specific pressure range, but when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. This change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma.

A pronounced cephalic fluid shift is one of the responses to exposure to the microgravity spaceflight environment. This project uses the well‐documented rat hindlimb suspension (HLS) model to test the hypothesis that this fluid shift is a causative factor underlying the ocular changes seen in astronauts during and following long‐duration spaceflight. This hypothesis follows from the fact that similar ocular effects are seen in Idiopathic Intracranial Hypertension (IIH) and are associated with increased intraocular pressure (IOP). In order to elucidate the roles played by age and sex in the relationship between a cephalic fluid shift and the regulation of intracranial pressure (ICP) and IOP, as well as visual system structure and function, three cohorts are under study: young adult females, young adult males, and older middle‐age males. Groups of animals are exposed to HLS durations of 0 (baseline), 7, 14, 28 and 90 days with 90 days of HLS being followed by equivalent intervals of recovery in a vivarium cage, i.e. either 0, 7, 14, 28 or 90 days. Each HLS subject has an age‐matched control maintained in the same room but in a vivarium cage. An LD 12:12 cycle is present and all subjects have ad lib access to food and water. This presentation represents a status report of this ongoing program. We have measured ICP in one group of subjects. ICP recording is underway for the other 2 groups. To date, the data identify a very small increase in ICP, which is maintained during HLS. Our hypothesis is that this increase in ICP could lead to morphological changes in visual structures similar to those seen previously in some astronauts following long duration missions. To this end, MRI was used to image the eyes and brains in all 3 groups at baseline and at the midpoint and endpoint of HLS and recovery. Data analysis indicates increased optic nerve sheath diameters which are most pronounced in the middle‐aged males yet also observed in younger males, as well as globe flattening in HLS. IOP continues to be measured in all animals under study. In general, there is a trend for increased IOP during HLS. Moreover, refractive error increases over 90 days of suspension. These preliminary results continue to be supportive of our hypothesis that an increase in ICP may underlie such ocular changes. Support or Funding Information Supported by NASA Grant NNX13AD94G.

An increasing number of studies indicate that the optic nerve head of the eye is sensitive not only to changes in intraocular pressure (IOP), but also to intracranial pressure (ICP). This study examines changes to optic nerve and retinal structure in a rat model in response to a range of IOP and ICP levels using optical coherence tomography. Furthermore, we examine the functional sequelae of these structural changes by quantifying the effect of pressure changes on the electroretinogram. IOP elevation (10–90 mmHg) induces progressive deformation of the optic nerve head and retinal surface (P < 0.05), compression of the retina (P < 0.05) and bipolar cell (b-wave), and retinal ganglion cell (scotopic threshold response) dysfunction (P < 0.05). Simultaneously altering ICP (−5 to 30 mmHg) modifies these IOP-induced responses, with lower ICP (−5 mmHg) exacerbating and higher ICP (15–30 mmHg) ameliorating structural and functional deficits. Thus, the balance between IOP and ICP (optic nerve pressure gradient, ONPG = IOP − ICP) plays an important role in optic nerve integrity. Structural and functional parameters exhibit a two-phase relationship to ONPG, with structural changes being more sensitive to ONPG modification (threshold = −0.6 to 11.3 mmHg) compared with functional changes (threshold = 49.7–54.6 mmHg). These findings have implications for diseases including glaucoma, intracranial hypertension, and long-term exposure to microgravity.

Current techniques used to measure intracranial pressure (ICP) are invasive and require surgical procedures in order to implant pressure catheters in brain ventricles. The amplitude of central retinal vein pulsations (RVPa) has been shown to be associated with the pressure gradient between intraocular pressure (IOP) and ICP. When IOP approaches ICP, the pressure gradient drops, leading to cessation of RVPa. In this study we aim to investigate this relationship and define a new method to estimate ICP non-invasively. 10 healthy subjects (mean age 35±10) with clear medical history were included in this study. Baseline IOP was measured (Goldman tonometers) and RVP recorded using Dynamic Vessel Analyser.IOP was decreased actively using 0.5% Iopidine and RVP recorded simultaneously every 15 minutes. Digital signal processing techniques were used to measure mean RVP peak-to-peak amplitude in each cardiac cycle at different IOP levels. Linear regression equations were used to extract a relation between IOP and RVPa and to estimate the pressure at which RVPa cease (i.e. RVPa=0). At this point ICP equals IOP. IOP and ICP pressure waveforms were simulated in order to estimate ICP continuously. Results show a linear relationship between RVPa and IOP such that RVP decreases with IOP reduction. Estimated ICP ranged between 2-13.7 mmHg, all falling in the normal physiological range (i.e. 0-15 mmHg). Analysis of retinal venous pulsation in accordance with IOP may introduce a novel approach for estimation of ICP non-invasively.

Intraocular pressure (IOP) fluctuation has recently been identified as a risk factor for glaucoma progression. Further, decreases in intracranial pressure (ICP), with postulated increases in the translaminar pressure gradient across the lamina cribrosa, has been reported in glaucoma patients. We hypothesized that circadian fluctuations in IOP and the translaminar pressure gradient are influenced, at least in part, by central autonomic regulatory neurons within the dorsomedial and perifornical hypothalamus (DMH/PeF). This study examined whether site-directed chemical stimulation of DMH/PeF neurons evoked changes in IOP, ICP, and the translaminar pressure gradient. The GABA(A) receptor antagonist bicuculline methiodide (BMI) was stereotaxically microinjected into the DMH/PeF region of isoflurane-anesthetized male Sprague-Dawley rats (n = 19). The resulting peripheral cardiovascular (heart rate [HR] and mean arterial pressure [MAP]), IOP, and ICP effects were recorded and alterations in the translaminar pressure gradient calculated. Chemical stimulation of DMH/PeF neurons evoked significant increases in HR (+69.3 ± 8.5 beats per minute); MAP (+22.9 ± 1.6 mm Hg); IOP (+7.1 ± 1.9 mm Hg); and ICP (+3.6 ± 0.7 mm Hg) compared with baseline values. However, the peak IOP increase was significantly delayed compared with ICP (28 vs. 4 minutes postinjection), resulting in a dramatic translaminar pressure gradient fluctuation. Chemical stimulation of DMH/PeF neurons evokes substantial increases in IOP, ICP, and the translaminar pressure gradient in the rat model. Given that the DMH/PeF neurons may be a key effector pathway for circadian regulation of autonomic tone by the suprachiasmatic nucleus, these findings will help elucidate novel mechanisms modulating circadian fluctuations in IOP and the translaminar pressure gradient.

Yoga is the most popular form of complementary therapy being practiced to maintain one’s physical and mental wellbeing. While yoga traditionally comprises advice for ethical lifestyle and spiritual practice, it is most often associated with physical postures (asanas), breathing techniques (pranayama), and meditation (dhyana). While these exercises are routinely safe, there are risks involved for certain patients including those suffering from or at risk of glaucoma. The effects of yoga on intraocular pressure (IOP) have been found to be bidirectional, and the exact mechanisms are not yet fully understood. The authors have reviewed literature to study the effect of yoga on IOP and glaucoma. They have observed a reduction of IOP in patients of glaucoma through Jyoti tratak (candle meditation) and slow yoga breathing exercises and a rapid increase in IOP immediately after head-down posture yoga.[1] Tratak kriya is said to lead to contraction and relaxation of ciliary muscles, which may possibly increase the aqueous humor outflow and subsequently decrease the IOP.[2] Dada et al.[3] have evaluated the effect of yoga and meditation on IOP, quality of life, stress markers, neurotrophins, and gene expression in patients with primary open-angle glaucoma and found an improvement in all parameters. On the other hand, progressive glaucomatous optic neuropathy and field loss in patients who regularly practiced Sirsasana (Headstand) has also been identified.[1,4,5] Four yogasanas [Adho Mukha Savasana (downward-facing dog), Uttanasana (standing forward bend), Halasana (plough pose), and Viparita Karani (legs-up-the-wall)] showed a 20–73.7% increase in IOP in all study subjects.[1] Yoga with head-down positions was associated with a rapid rise in IOP in glaucoma and healthy eyes and with the body vertical, with a doubling of the IOP, remaining elevated as long as the position was maintained.[1] Mani Baskaran et al.[6] observed a twofold increase in IOP during Sirsasana, which was maintained during the posture in all age groups irrespective of their ocular characteristics. Valsalva maneuver is known to affect IOP; so it is expected that breath-holding yogic exercises are likely to cause IOP elevation. Forced unilateral nostril breathing has also been observed to affect IOP significantly.[7] Rakstyte et al.[8] studied an impact on IOP before, during, and after Matsyasana (fish yoga pose) and found an increased IOP in head- down position which returns to the initial value shortly after. A case series by Mehrdad Malihi et al.[9] to study the effect of different body and head positions on IOP shows a lower measurement while sitting with a neutral neck position and a rise in IOP in all other positions. Acute angle-closure glaucoma attacks often precipitated by prone-position yoga exercises suggest that this position probably increases pupillary block in “at risk” eyes by causing the lens to fall onto the iris, which has been the principle of the prone provocative test for decades. Certain questions, however, remain unanswered. It is unclear whether yoga has any sustained effects on the IOP and optic nerve. Further research is needed to fully comprehend the mechanisms by which yoga exerts its effects and determine the types, optimal duration, and frequency of yoga practice for glaucoma patients. Future studies are also warranted to ascertain whether yoga-associated IOP changes are associated with parallel changes in perimetry and nerve fiber thickness and changes in cerebrospinal fluid pressure, blood pressure in lamina cribrosa capillaries, and the ocular blood flow. It is difficult to establish direct causality between different yogic postures and glaucomatous progression, but in patients with pre-existing glaucomatous optic neuropathy, dramatic changes in IOP can definitely be harmful. Inquiring about the practice of yoga in cases of unexplained progression despite an apparently well-controlled IOP can, therefore, be an important consideration. Relaxation and meditative aspects of yoga may help to reduce stress and improve the overall well-being of an individual which can be indirectly beneficial. The key is to “keep the head above the heart at all times.” It is also important to note that yoga should not replace traditional glaucoma treatment but rather be practiced/advised as a complementary therapy and glaucoma patients should consult their healthcare provider before beginning any new exercise or relaxation program, including yoga.

Primary open angle glaucoma (POAG) is a chronic disease characterized by progressive optic nerve damage and irreversible loss of vision, often diagnosed at late stages. Elevated intraocular pressure (IOP) is the major risk factor for its onset and progression while older age, myopia, genetic factors, blood pressure (BP), and reduced ocular blood flow (OBF) have also been linked to the disease. Different forms of exercise are known to have significant, but variable, effects on IOP, BP, ocular perfusion pressure (OPP), OBF and oxygen metabolism, and ultimately the risk for development and progression of POAG. While population-based studies lack agreement regarding the relationship between exercise and POAG status, data suggests that resistance training causes a short-term increase in IOP, BP, and OPP. Conversely, aerobic exercise has been shown to cause a short-term decrease in IOP and increase in BP and OPP. Research also suggests that following an exercise program over an extended period may lead to a long-term decrease in IOP, however its cessation results in a prompt return to baseline levels. Data suggests normal vascular autoregulation ensures minimal change in OBF following extended exercise unless OPP rises ∼70% above baseline. Although exercise may alter IOP, BP, and OBF, both acutely and chronically, it is currently uncertain if physical activity significantly alters risk for the onset and progression of POAG.

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.