Visual Impairment Intracranial Pressure (VIIP) [aka Microgravity Ocular Syndrome (MOS)]
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Tarver, William↗
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Transient Increases in Intracranial Pressure After Soccer Heading
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Justin Lee↗
Noninvasive indicators of intracranial pressure before, during, and after long-duration spaceflight
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Jessica V. Jasien↗
Effect of Strict Head Down Tilt Bedrest on Pituitary Gland Height
BACKGROUND Pituitary gland deformity and loss of pituitary height have been identified in astronauts postflight, hypothesized to be related to increased intracranial pressure or intracranial pressure pulsatility exposure from prolonged weightlessness. Microgravity-induced chronic headward fluid shift has been suggested as a root cause of intracranial compliance changes leading to altered intracranial pressure dynamics. Elevated intracranial pressure or pressure pulsatility is theorized to promote the development of an arachnoid diverticulum, which herniates into the pituitary fossa via a defect in the diaphragma sellae compressing the pituitary gland. We aimed to determine if chronic headward fluid induced by strict head-down tilt bed rest (HDTBR) can cause similar quantitative changes in pituitary gland height. METHODS Control group data from two 6-degree HDTBR studies were analyzed (SANS CM and AGBRESA). The AGBRESA study collected MRI data at Baseline, 14 days into HDTBR (HDTBR-14), 52 days into HDTBR (HDTBR-52), and three days into Recovery (R+ 3) and included eight healthy adults (2 women), age = 33 ± 8 years. The SANS CM collected MRI data at Baseline, 15 days into HDTBR (HDTBR-15), 29 days into HDTBR (HDTBR-29), and 12 days into Recovery (R+12) and included twelve healthy adults (4 women), age = 34 ± 9 years. Pituitary gland height was evaluated using a sagittal, 3D T1-MPRAGE sequence obtained on a dedicated 3T Siemens Biograph MRI scanner using a 32-channel head coil. Following the reconstruction of a true orthogonal sagittal plane of the pituitary gland using a 3D multiplanar reconstruction tool (Horosproject.org), the anterior pituitary mid-gland height at the pituitary stalk level was quantified according to the methodology described by Kramer et al. . A paired t-test was used to evaluate changes from the baseline measurements. FINDINGS The mean height of the pituitary gland at baseline was 6.5 ± 1.7 mm (AGBRESA) and 5.7 ± 1.6 mm (SANS CM). From baseline measurements, the SANS CM STUDY data showed a decrease in mean pituitary height of 0.3 mm (p=.011) at HDTBR-15, 0.5 mm at HDTBR-29 (p<.001) and 0.2 mm at R+12 (p=.02). From baseline measurements, the AGBRESA data showed a decrease in mean pituitary height of 0.3 mm (p=.06) at HDTBR-14, 0.6 mm at HDTBR-52 (p<.002) and 0.2 mm at R+3 (p=.13). CONCLUSION HDTBR results in progressive loss of pituitary height, which is most severe with the longest HDTBR exposure. Early pituitary height loss was the same at HDTBR-14 (AGBRESA) and HDTBR-15 (SANS CM). Residual pituitary height loss was the same at R+12 and R+3 but only significant in the latter (SANS CM). The degree of pituitary height loss at HDTBR-52 replicates the 0.6 mm height loss found in long-duration astronauts after approximately six months of microgravity exposure (p<.01, preflight mean height=5.9 mm). The hormonal effects of pituitary height loss are unknown in astronauts and HDTBR subjects and should be investigated in future studies. Future work will examine the individual variability in the loss of pituitary gland height and whether those changes are associated with other SANS findings, such as optic disc edema.
L A Kramer↗
Influence of Population Variation of Physiological Parameters in Computational Models of Space Physiology
The earliest manifestations of Visual Impairment and Intracranial Pressure (VIIP) syndrome become evident after months of spaceflight and include a variety of ophthalmic changes, including posterior globe flattening and distension of the optic nerve sheath. Prevailing evidence links the occurrence of VIIP to the cephalic fluid shift induced by microgravity and the subsequent pressure changes around the optic nerve and eye. Deducing the etiology of VIIP is challenging due to the wide range of physiological parameters that may be influenced by spaceflight and are required to address a realistic spectrum of physiological responses. Here, we report on the application of an efficient approach to interrogating physiological parameter space through computational modeling. Specifically, we assess the influence of uncertainty in input parameters for two models of VIIP syndrome: a lumped-parameter model (LPM) of the cardiovascular and central nervous systems, and a finite-element model (FEM) of the posterior eye, optic nerve head (ONH) and optic nerve sheath. Methods: To investigate the parameter space in each model, we employed Latin hypercube sampling partial rank correlation coefficient (LHSPRCC) strategies. LHS techniques outperform Monte Carlo approaches by enforcing efficient sampling across the entire range of all parameters. The PRCC method estimates the sensitivity of model outputs to these parameters while adjusting for the linear effects of all other inputs. The LPM analysis addressed uncertainties in 42 physiological parameters, such as initial compartmental volume and nominal compartment percentage of total cardiac output in the supine state, while the FEM evaluated the effects on biomechanical strain from uncertainties in 23 material and pressure parameters for the ocular anatomy. Results and Conclusion: The LPM analysis identified several key factors including high sensitivity to the initial fluid distribution. The FEM study found that intraocular pressure and intracranial pressure had dominant impact on the peak strains in the ONH and retro-laminar optic nerve, respectively; optic nerve and lamina cribrosa stiffness were also important. This investigation illustrates the ability of LHSPRCC to identify the most influential physiological parameters, which must therefore be well-characterized to produce the most accurate numerical results.
biomechanics↗
Visual Impairment and Intracranial Hypertension: An Emerging Spaceflight Risk
What is the risk? Given that astronauts exposed to microgravity experience a cephalad fluid shift, and that both symptomatic and asymptomatic astronauts have exhibited optic nerve sheath edema on MRI, there is a high probability that all astronauts have some degree of increased intracranial pressure (ICP; intracranial hypertension), and that those susceptible (via eye architecture, anatomy, narrow optic disc) have a high likelihood of developing papilledema (optic disc edema, globe flattening), choroidal folds, and/or hyperopic shifts and that the degree of edema may determine long-term or permanent vision impairment or loss. Back to back panels on this topic have been developed to address this emerging risk. The first panel will focus on the 6 clinical cases with emphasis on ophthalmic findings and imaging techniques used pre-, in-, and post-flight. The second panel will discuss the operational mitigation and medical requirements, the potential role of CO2 on ISS, and the research approach being developed. In total these back to back panels will explore what is known about this risk, what has been done immediately to address it, and how an integrated research model is being developed.
Fogarty, Jennifer A.↗
Are Medications Involved in Vision and Intracrancial Pressure Changes Seen in Spaceflight?
The Food and Drug Association Adverse Event Reports (FDA AER) from 2009-2011 were used to create a database from millions of known and suspected medication-related adverse events among the general public. Vision changes, sometimes associated with intracranial pressure changes (VIIP), have been noted in some long duration crewmembers. Changes in vision and blood pressure (which can subsequently affect intracranial pressure) are fairly common side effects of medications. The purpose of this study was to explore the possibility of medication involvement in crew VIIP symptoms. Reports of suspected medication-related adverse events may be filed with the Food and Drug Administration (FDA) by medical professionals or consumers. Quarterly compilations of these reports are available for public download. Adverse Event Reporting System (AERS) reports from 1/1/2009- 6/30/2012 were downloaded and compiled into a searchable database for this study. Reports involving individuals under the age of 18 and older than 65 were excluded from this analysis. Case reports involving chronic diseases such as cancer, diabetes, multiple sclerosis and other serious conditions were also excluded. A scan of the medical literature for medication-related VIIP-like adverse events was used to create a list of suspect medications. These medications, as well as certain medications used frequently by ISS crew, were used to query the database. Queries for use of suspected medications were run, and the nature of the symptoms reported in those cases were tabulated. Symptoms searched in the FDA AERS were chosen to include the typical symptoms noted in crewmembers with VIIP. Vision symptoms searched were: visual acuity reduced, visual impairment, and vitreous floaters. Pressure changes included: abnormal sensation in eye, intracranial pressure increased, intraocular pressure increased, optic neuritis, optic neuropathy, and papilloedema. Limited demographic information is included with the FDA AERS; relevant data were also sorted by age and sex from each report. RESULTS Steroid-containing oral contraceptives had the highest number of reports associated with vision (n=166) and pressure symptoms (n=54). Corticosteroid-containing medications were also high; prednisone, for example, had 137 reports of vision issues and 79 of pressure issues. Pain relievers were also a medication class with vision and pressure-related adverse events reported. Common over-the-counter medications such as acetaminophen, aspirin and ibuprofen each had multiple reports for both vision and pressure symptoms. Antimicrobial medications ciprofloxacin and diflucan were also associated with a number of vision and pressure-related AERS. Unexpectedly, pseudoephedrine and promethazine were mentioned in fewer than 20 reports each over the 3.5 years of data examined. The FDA AERS represents a wealth of data, but there are several limitations to its use. The data are entered by the public or medical professionals, but are not checked for accuracy or completeness and may even be entered multiple times. The causal relationship between a particular adverse event and a particular medication is not tested. The cases represent a broad spectrum of demographics, occupations, and health histories, and thus do not model the astronaut population well. There is no information on the frequency of use of a medication for comparison purposes; it is not possible to assign a rate for any particular adverse event. Nonetheless, there are compelling trends. Use of corticosteroid-containing medications, pain relievers (even over-the-counter), and oral contraceptives were associated with higher numbers of vision- or intracranial pressure-related adverse events. In general, there were more vision problems than pressure problems reported. Certain medications that were once suspected of playing a role in the crew VIIP syndrome, namely pseudoephedrine and promethazine, were found to have extremely low numbers of VIIP-like AERS in the FDA data. However, crew use of corticosteroid-containing medications and pain relievers may warrant additional investigation
Faust, K. M.↗
Optic Nerve Sheath Diameter: Translating a Terrestrial Focused Technique Into a Clinical Monitoring Tool for Space Flight
Emergency medicine physicians recently adopted the use of ultrasonography to quickly measure optic nerve sheath diameter (ONSD) as concomitant with increased intracranial pressure. NASA Space and Clinical Operations Division has been using ground and on-orbit ultrasound capabilities since 2009 to consider this anatomical measure as a proxy for intracranial pressure in the microgravity environment. In the terrestrial emergency room population, an ONSD greater than 0.59 cm is considered highly predictive of elevated intracranial pressure. However, this cut-off limit is not applicable to the spaceflight setting since over 50% of US Operating Segment (USOS) astronauts have an ONSD greater than 0.60 cm even before missions. Crew Surgeon clinical decision-making is complicated by the fact that many astronauts have history of previous spaceflights. Data will be presented characterizing the distribution of baseline ONSD in the astronaut corps, longitudinal trends in-flight, and the predictive power of this measure related to increased intracranial pressure outcomes.
Mason, Sara S.↗
The Impact of Ocular Pressures, Material Properties and Geometry on Optic Nerve Head Deformation
Alteration in intracranial pressure (ICP) has been associated with various diseases that cause visual impairment, including glaucoma, idiopathic intracranial hypertension and Visual Impairment and Intracranial Pressure (VIIP) syndrome. However, how changes in ICP lead to vision loss is unclear, although it is hypothesized to involve deformations of the tissues in the optic nerve head (ONH). Recently, understanding the effect of ICP alterations on ocular tissues has become a major concern for NASA, where 42 of astronauts that partake in long duration space missions suffer from VIIP syndrome. Astronauts with VIIP syndrome suffer from visual impairment and changes in ocular anatomy that persist after returning to earth (1). It is hypothesized that the cephalad fluid shift that occurs upon entering microgravity increases ICP, which leads to an altered biomechanical environment in the posterior globe and optic nerve sheath, and subsequently VIIP syndrome. Our goal was to develop a finite element (FE) model to simulate the acute effects of elevated ICP on the posterior eye. Here, we simulated how inter-individual differences affect the deformation of ONH tissues. Further, we examined how several different geometries influenced deformations when exposed to elevated ICP.
mathematical models↗
Optic Nerve Sheath Mechanics in VIIP Syndrome
Visual Impairment and Intracranial Pressure (VIIP) syndrome results in a loss of visual function and occurs in astronauts following long-duration spaceflight. Understanding the mechanisms that lead to the ocular changes involved in VIIP is of critical importance for space medicine research. Although the exact mechanisms of VIIP are not yet known, it is hypothesized that microgravity-induced increases in intracranial pressures (ICP) drive the remodeling of the optic nerve sheath, leading to compression of the optic nerve which in turn may reduce visual acuity. Some astronauts present with a kink in the optic nerve after return to earth, suggesting that tissue remodeling in response to ICP increases may be taking place. The goal of this work is to characterize the mechanical properties of the optic nerve sheath (dura mater) to better understand its biomechanical response to increased ICP.
microgravity↗
Fluid Shifts
Introduction. NASA's Human Research Program is focused on addressing health risks associated with long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but now more than 50 percent of ISS astronauts have experienced more profound, chronic changes with objective structural findings such as optic disc edema, globe flattening and choroidal folds. These structural and functional changes are referred to as the visual impairment and intracranial pressure (VIIP) syndrome. Development of VIIP symptoms may be related to elevated intracranial pressure (ICP) secondary to spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight and to determine if a relation exists with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as any VIIP-related effects of those shifts, are predicted by the crewmember's pre-flight status and responses to acute hemodynamic manipulations, specifically posture changes and lower body negative pressure. Methods. We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, and calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography; intraocular pressure; 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness; Doppler ultrasound of ophthalmic and retinal arteries and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, otoacoustic emissions). Pre- and post-flight, acute head-down tilt will induce cephalad fluid shifts, whereas lower body negative pressure will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome. Discussion. Ten subjects have consented to participate in this experiment, including the recent One-Year Mission crewmembers, who have recently completed R plus180 testing; all other subjects have completed pre-flight testing. Preliminary results from the One-Year Mission crewmembers will be presented, including measures of ocular structure and function, vascular dimensions, fluid distribution, and non-invasive estimates of intracranial pressure.
Stenger, M. B.↗
Non-invasive method of measuring cerebral spinal fluid pressure
The invention provides a method of non-invasively determining intracranial pressure from measurements of an eye. A parameter of an optic nerve of the eye is determined, along with an intraocular pressure of the eye. The intracranial pressure may be determined from the intraocular pressure and the parameter.
Borchert, Mark S.↗
NASA's Spaceflight Visual Impairment and Intracranial Hypertension Research Plan: An accelerated Research Collaboration
To date six long duration astronauts have experienced in flight visual changes and post flight signs of optic disc edema, globe flattening, choroidal folds, hyperoptic shifts and or raised intracranial pressure. In some cases the changes were transient while in others they are persistent with varying degrees of visual impairment. Given that all astronauts exposed to microgravity experience a cephalad fluid shift, and that both symptomatic and asymptomatic patients have exhibited optic nerve sheath edema on MRI, there is a high probability that all astronauts develop in-flight idiopathic intracranial hypertension to some degree. Those who are susceptible, have an increased likelihood of developing treatment resistant papilledema resulting in visual impairment and possible long-term vision loss. Such an acquired disability would have a profound mission impact and would be detrimental to the long term health of the astronaut. The visual impairment and increased intracranial pressure phenomenon appears to have multiple contributing factors. Consequently, the working "physiological fault bush" with elevated intracranial pressure at its center, is divided into ocular effects, and CNS and other effects. Some of these variables have been documented and or measured through operational data gathering, while others are unknown, undocumented and or hypothetical. Both the complexity of the problem and the urgency to find a solution require that a unique, non-traditional research model be employed such as the Accelerated Research Collaboration(TM) (ARC) model that has been pioneered by the Myelin Repair Foundation. In the ARC model a single entity facilitates and manages all aspects of the basic, translational, and clinical research, providing expert oversight for both scientific and managerial efforts. The result is a comprehensive research plan executed by a multidisciplinary team and the elimination of stove-piped research. The ARC model emphasizes efficient and effective communication between management and investigators; and real-time sharing of scientific discoveries in an effort to solve complex problems.
Otto, Christian↗
Development of a new, completely implantable intraventricular pressure meter and preliminary report of its clinical experience
A completely implantable intracranial pressure sensor designed for long-term measurement of intraventricular pressure in hydrocephalic patients is described. The measurement principal of the device is discussed along with the electronic and component structure and sources of instrument error. Clinical tests of this implanted pressure device involving both humans and animals showed it to be comparable to other methods of intracranial pressure measurement.
Osaka, K.↗
VIIP: Central Nervous System (CNS) Modeling
Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.
intraocular pressure↗
Microgravity-Driven Optic Nerve/Sheath Biomechanics Simulations
Visual Impairment and Intracranial Pressure (VIIP) syndrome is a concern for long-duration space flight. Current thinking suggests that the ocular changes observed in VIIP syndrome are related to cephalad fluid shifts resulting in altered fluid pressures [1]. In particular, we hypothesize that increased intracranial pressure (ICP) drives connective tissue remodeling of the posterior eye and optic nerve sheath (ONS). We describe here finite element (FE) modeling designed to understand how altered pressures, particularly altered ICP, affect the tissues of the posterior eye and optic nerve sheath (ONS) in VIIP. METHODS: Additional description of the modeling methodology is provided in the companion IWS abstract by Feola et al. In brief, a geometric model of the posterior eye and optic nerve, including the ONS, was created and the effects of fluid pressures on tissue deformations were simulated. We considered three ICP scenarios: an elevated ICP assumed to occur in chronic microgravity, and ICP in the upright and supine positions on earth. Within each scenario we used Latin hypercube sampling (LHS) to consider a range of ICPs, ONH tissue mechanical properties, intraocular pressures (IOPs) and mean arterial pressures (MAPs). The outcome measures were biomechanical strains in the lamina cribrosa, optic nerve and retina; here we focus on peak values of these strains, since elevated strain alters cell phenotype and induce tissue remodeling. In 3D, the strain field can be decomposed into three orthogonal components, denoted as first, second and third principal strains. RESULTS AND CONCLUSIONS: For baseline material properties, increasing ICP from 0 to 20 mmHg significantly changed strains within the posterior eye and ONS (Fig. 1), indicating that elevated ICP affects ocular tissue biomechanics. Notably, strains in the lamina cribrosa and retina became less extreme as ICP increased; however, within the optic nerve, the occurrence of such extreme strains greatly increased as ICP was elevated (Fig. 2). In particular, c. 48 of simulations in the elevated ICP condition showed peak strains in the optic nerve that exceeded the strains expected on earth. Such extreme strains are likely important, since they represent a larger signal for mechano-responsive resident cells [2]. The models predicted little to no anterior motion of the prelaminar neural tissue (optic nerve swelling, or papilledema, secondary to axoplasmic stasis), typically seen with elevated ICP. Specialized FE models to capture axoplasmic stasis would be required to study papilledema. These results suggest that the most notable effect of elevated ICP may occur via direct optic nerve loading, rather than through connective tissue deformation. These FE models can inform the design of future studies designed to bridge the gap between biomechanics and pathophysiological function in VIIP.
biomechanics↗
Finite Element Modeling of the Posterior Eye in Microgravity
Microgravity experienced during spaceflight affects astronauts in various ways, including weakened muscles and loss of bone density. Recently, visual impairment and intracranial pressure (VIIP) syndrome has become a major concern for space missions lasting longer than 30 days. Astronauts suffering from VIIP syndrome have changes in ocular anatomical and visual impairment that persist after returning to earth. It is hypothesized that a cephalad fluid shift in microgravity may increase the intracranial pressure (ICP), which leads to an altered biomechanical environment of the posterior globe and optic nerve sheath (ONS).Currently, there is a lack of knowledge of how elevated ICP may lead to vision impairment and connective tissue changes in VIIP. Our goal was to develop a finite element model to simulate the acute effects of elevated ICP on the posterior eye and optic nerve sheath. We used a finite element (FE) analysis approach to understand the response of the lamina cribrosa and optic nerve to the elevations in ICP thought to occur in microgravity and to identify which tissue components have the greatest impact on strain experienced by optic nerve head tissues.
intraocular pressure↗
Integrated Model of the Eye/Optic Nerve Head Biomechanical Environment
Visual Impairment and Intracranial Pressure (VIIP) syndrome is a concern for long-duration space flight. Previously, it has been suggested that ocular changes observed in VIIP syndrome are related to the cephalad fluid shift that results in altered fluid pressures [1]. We are investigating the impact of changes in intracranial pressure (ICP) using a combination of numerical models, which simulate the effects of various environment conditions, including finite element (FE) models of the posterior eye. The specific interest is to understand how altered pressures due to gravitational changes affect the biomechanical environment of tissues of the posterior eye and optic nerve sheath. METHODS: Additional description of the numerical modeling is provided in the IWS abstract by Nelson et al. In brief, to simulate the effects of a cephalad fluid shift on the cardiovascular and ocular systems, we utilized a lumped-parameter compartment model of these systems. The outputs of this lumped-parameter model then inform boundary conditions (pressures) for a finite element model of the optic nerve head (Figure 1). As an example, we show here a simulation of postural change from supine to 15 degree head-down tilt (HDT), with primary outcomes being the predicted change in strains at the optic nerve head (ONH) region, specifically in the lamina cribrosa (LC), retrolaminar optic nerve, and prelaminar neural tissue (PLNT). The strain field can be decomposed into three orthogonal components, denoted as the first, second and third principal strains. We compare the peak tensile (first principal) and compressive (third principal) strains, since elevated strain alters cell phenotype and induces tissue remodeling. RESULTS AND CONCLUSIONS: Our lumped-parameter model predicted an IOP increase of c. 7 mmHg after 21 minutes of 15 degree HDT, which agreed with previous reports of IOP in HDT [1]. The corresponding FEM simulations predicted a relative increase in the magnitudes of the peak tensile and compressive strains in the lamina cribrosa of 42 and 43, respectively (Fig. 2). The corresponding changes in the optic nerve strains were 17 and 39, while in the PLNT they were 47 and 43. These magnitudes of relative elevations in peak strains may induce a phenotypic response in resident mechano-responsive resident cells [2]. This approach may be expanded to investigate other environmental changes (e.g. parabolic flight). Through our VIIP SCHOLAR project, we will validate and improve these integrated models by measuring patient-specific changes in optic nerve sheath geometry in patients with idiopathic intracranial hypertension before and after lumbar puncture and CSF removal.
biomechanics↗