Visual Impairment Intracranial Pressure Project
Frey MA. Research Progress Reports from the NASA Human Research Program: visual impairment intracranial pressure project. Aviat Space Environ Med 2013; 84:163–4.
These summaries are written for NASA and prepared for the journal by Mary Anne Frey, Ph.D., with the support of NASA’s Human Research Program Office and are intended to alert the scientific community to ongoing work in Space Medicine. Original sources for the material may include journal articles, NASA Technical Reports, internal NASA documents, and personal communications from Principal Investigators.
Since the earliest human spaceflights, it has been known that when exposed to the microgravity environment, astronauts experience a shift of fluids from their lower body (more than a liter from each leg) to the chest and head. Evidence includes signs and symptoms such as reduced size of the legs, puffy faces, distended jugular veins, increased stroke volume and cardiac output, headaches, nasal stuffiness, and a feeling of head fullness. This microgravity-induced fluid shift is reversed on return to gravity, causing orthostatic intolerance, a consequence that has been well studied. Recently, evidence is accumulating that the cephalad fluid shift may have more serious consequences for spaceflight crewmembers than previously recognized, especially for crewmembers on long-duration spaceflights. As mission duration on ISS has lengthened, reports of changes in astronauts’ vision during spaceflight have increased and NASA Space Life Sciences Medical Operations has instituted greater pre-, in-, and postflight visual testing. As a result, varying degrees of anatomic and functional changes were identified in 10 astronauts who completed long-duration missions. Degradation in near vision, which in some cases continued for longer than 1 yr post mission, has also been identified in other astronauts with long- and/or short-duration flights. The ophthalmic findings in the long-duration crewmembers may be related to idiopathic intracranial hypertension, a syndrome identified on Earth, which suggests that an increase in intracranial pressure (ICP), caused by the headward fluid shift that occurs with exposure to microgravity, may be involved. The syndrome has been designated “visual impairment intracranial pressure” (VIIP). This report describes the evidence for this syndrome and efforts to understand the causes and underlying physiology and to develop effective countermeasures and treatment.
1. Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, et al. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 2011; 118:2058–69.
2. Visual Impairment Intracranial Pressure Summit Report. Houston, TX: NASA Johnson Space Center; February 8-10, 2011; retrieved on June 26, 2012, from http://humanresearchroadmap.nasa.gov/Risks/?i=105.
3. Kramer LA, Sargsyan AE, Hasan KM, Polk JD, Hamilton DR. Orbital and intracranial effects of microgravity: findings at 3-T MR imaging. Radiology 2012; 263:819-27. DOI: 10.1148/radiol. 12111986.
Introduction and Methods
Ophthalmic Findings in Seven Astronauts After Long-Duration Spaceflight (1)
Pre- and postflight eye examinations have been routine for all crewmembers for many years. Since 1989, crewmembers have been asked whether they had perceived any changes in their near or distant vision during their missions. As reports of changes in vision grew, NASA Johnson Space Center (JSC) Space Life Sciences Medical Operations instituted a process to identify the cause(s), which included ophthalmic procedures such as dilated fundus examinations with binocular ophthalmoscopy, cycloplegic refraction, optical coherence tomography (OCT), magnetic resonance imaging (MRI) of orbits, and fundus photos of astronauts before and after space missions.
As a result, they identified seven astronauts who returned from long-duration spaceflight during the past several years presenting with varying degrees of disk edema, globe flattening, choroidal folds, cotton wool spots, nerve fiber layer thickening, and decreased near vision. “The similarities of the setting and clinical features of these patients suggests a common etiology inherent to the microgravity environment.”
In addition, 300 crewmembers of short- and long-duration spaceflights completed postflight questionnaires that indicated that approximately 23% of astronauts on short-duration missions and 48% of astronauts on long-duration missions experienced degradation in near vision, which has continued for years in some cases.
Mader et al. (1) described the ophthalmic findings in the “long-duration” crewmembers and noted similarities to idiopathic intracranial hypertension (IIH), which is well defined on the ground and has similar findings. This would seem to indicate the syndrome in spaceflight may involve a rise in cephalic venous pressure brought about by microgravity fluid shifts. However, they also state that, “There are significant arguments against increased intracranial pressure being the sole etiology in the cases we describe.” They went on to describe the pros and cons of other potential etiologies of the observed anatomical and visual changes. In conclusion, they state that “NASA has initiated a protocol to acquire prospective preflight, in-flight, and postflight data on all future astronauts to define the exact origin of these potentially harmful ocular changes.”
The Visual Impairment Intracranial Pressure Summit (2)
February 8-10, 2011, NASA JSC Space Life Sciences Directorate convened a summit attended by approximately 75 experts representing multiple disciplines and including non-NASA clinicians, professors from various academic institutions, and NASA civil servants and contractors “to solicit input and recommendations from a diverse group of experts from the fields of medicine and research and to function as the forum in which the scope of the problem is defined” (2). A Research and Clinical Advisory Panel (RCAP) was created to provide guidance for the future research project.
The VIIP Panel stated “that the vision, physiological, and anatomical changes observed in long duration astronauts as documented in the seven cases presented are unlike any clinical entity they have seen as a collective.” While blindness near term is unlikely, the long-term sequelae are unknown. The VIIP Panel made numerous recommendations in two categories: clinical input and fundamental research. The VIIP Project Team with guidance of the RCAP will determine: “1) what can be immediately implemented or requires additional research development for clinical management and 2) prioritization of objectives captured in the fundamental research areas.” The VIIP Panel said NASA was adequately monitoring and documenting changes in vision and anatomy of the eye. This panel recommended that a higher resolution in-flight retinal imaging system that would allow early diagnosis be instituted. They emphasized the need to correlate the in-flight ultrasound imaging system with MRI (the gold standard) and recommended that greater use be made of OCT, a new accurate, precise, non-invasive imaging technology that could be an onboard ‘early warning system.’ After considering all evidence, the panel concluded that the increase in ICP may not be the sole cause of the observed changes and that identification of other possible causes should be pursued, including research based on anatomy, physiology, genetics, and epigenetics (to detect genes affected by the spaceflight environment).
The NASA JSC Space Medicine Division (SD) and the VIIP project have collaborated to increase pre-, in-, and postflight medical testing of all astronauts to determine the existence and degree of the ophthalmic and intracranial pressure alterations. This includes addition of an in-flight video funduscope for imaging, a state-of-the-art tonometer, and pre-, in-, and postflight OCT exams. Procedures for eye ultrasound are being refined and several devices for noninvasive clinical evaluation of ICP are being evaluated for future in-flight use. These capabilities will allow for accurate in-flight assessment of VIIP-related physiological changes and provide information for individual medical decisions if necessary.
Since the summit, RCAP members have been selected, the research scope has been drafted, and the collaborative research team is being developed. Operational activities are continuing along with data-mining, case definition, and development of clinical practice guidelines for the treatment of spaceflight-induced visual impairment/increased intracranial pressure.
Introduction and Methods
Additional MRI Findings (3)
Kramer et al. (3) used quantitative and qualitative techniques “to identify intraorbital and intracranial abnormalities in astronauts previously exposed to microgravity.” This study extended magnetic resonance (MRI) studies to a larger group of astronauts, including data from short-duration flights, and added analyses of the retrolaminar optic nerve, optic nerve sheath morphology, and the pituitary gland. In addition, “cerebrospinal fluid (CSF) opening pressure was measured by means of lumbar puncture … and with use of a column manometer” as a measure of ICP in four subjects.
Two groups of astronauts were included: Group 1 (total flight days averaged 108 ± 100 d) had 27 astronauts whose postflight examination data (from 2009 through 2010) were used irrespective of time elapsed (606 ± 822 d) or any symptoms (with one exception); Group 2 (total flight days averaged 130 ± 121 d) included 8 astronauts who had a repeat study after an additional mission and were examined 6.5 ± 9.6 d after return.
“Retrospective MR analysis of 27 astronauts exposed to microgravity revealed various combinations of optic nerve sheath distension, posterior globe flattening, optic disc protrusion, increased OND (optic nerve diameter), and moderate or greater concavity of the pituitary gland. Optic nerve sheath diameter (ONSD) and optic nerve diameter (OND) were at an elevated level consistent with research indicating increased ICP in some.” “Posterior globe flattening was seen in seven of the 27 astronauts (26%), optic nerve protrusion in four (15%), and moderate concavity of the pituitary dome with posterior stalk deviation in three (11%) without additional intracranial abnormalities. Retrolaminar OND increased linearly relative to ONSD. A central area of T2 hyperintensity was identifiable in 26 of the 27 astronauts (96%) and increased in diameter in association with kinking of the optic nerve sheath.” Several of these results are consistent with research indicating increased intracranial pressure, including elevated optic nerve sheath diameters, posterior globe flattening, and concavity of the pituitary gland, which are indicators of raised intracranial pressure in IIH. “There was no evidence of vasogenic edema, hydrocephalus, mass lesions, or central venous thrombosis.”
These investigators conclude that “the constellation of MR findings alone suggests that intracranial hypertension is an important component, drawing similarities to IIH and substantiated by direct CSF pressure measurements in four astronauts after flight.” However, they add “The absence of abnormal findings in a large proportion of astronauts suggests a variable biologic response to the spaceflight environment and warrants a search for risk factors associated with clinically relevant disease.”
VIIP is considered a major risk for future human spaceflight. Space Medicine and the Long Term Surveillance of Astronaut Health (LSAH) have undertaken a data review of health parameters, including markers of vascular health, in an effort to identify occupational risk factors. The recently reported knowledge summarized here concerning revelations about deleterious visual and cerebral effects of exposure to the microgravity environment will impact the future of human spaceflight and the brave men and women who will venture forth. Efforts of the scientific community are already increasing our knowledge and understanding to some extent while raising more questions to be answered. In the long run, these efforts will surely provide valuable information to benefit the space community and the Earth-bound population as well.
This research was funded by the Human Research Program, National Aeronautics and Space Administration (NASA).
Volume 84, Issue 2, pages 163-164
Reprint & Copyright © by the Aerospace Medical Association, Alexandria, VA.