Prospective Observational Study of Ocular Health in ISS Crews (Ocular Health) - 07.29.14
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The Prospective Observational Study of Ocular Health in ISS Crews (Ocular Health) protocol aims to systematically gather physiological data to characterize the Risk of Microgravity-Induced Visual Impairment/Intracranial Pressure on crewmembers assigned to a 6 month ISS increment. The data collected will mirror Medical Requirements Integration Documents (MRID) requirements and testing performed during annual medical exams with an increase in the frequency of in-flight and postflight testing to more accurately assess changes that occur in the visual, vascular, and central nervous systems upon exposure to microgravity and the resulting fluid shifts. Monitoring in-flight visual changes, in addition to postflight recovery, is the main focus of this protocol.
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OpNom Ocular Health
Johnson Space Center, Human Research Program, Houston, TX, United States
Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)
Human Exploration and Operations Mission Directorate (HEOMD)
Earth Benefits, Scientific Discovery, Space Exploration
ISS Expedition Duration
March 2013 - Ongoing
Previous ISS Missions
The purpose of this study is to collect evidence to characterize the risk and define the visual changes, vascular changes, and central nervous system (CNS) changes, including intracranial pressure, observed during -long-duration exposure to microgravity, including postflight time course for recovery to baseline. This study will gather information that can be used to assess the risk of Microgravity-Induced Visual Impairment/Intracranial Pressure (VIIP) and guide future research needs.
1. It is expected that some crewmembers will experience meaningful and detectable in-flight changes in at least one or more of the following: clarity of vision (visual acuity), pressure inside the eyeball (intraocular pressure), swelling of the optic disc (optic disc edema or papilledema), folds in the vascular layer of the eye (choroidal folds), optic nerve sheath distention, elongation of the optic nerve resulting from an increase in cerebrospinal fluid or CSF (optic nerve tortuosity), optic nerve-to-sheath ratio, flattening of the back part of the eye (globe flattening), and retinal "cotton-wool spots" (retinal nerve cells damaged by lack of blood flow), cardiovascular and cerebrovascular compliance and intracranial pressure.
2. It is expected that some crewmembers will experience meaningful pre- to postflight changes in one or more of the following: visual acuity, intraocular pressure, optic disc edema (papilledema), retinal nerve fiber layer, choroidal folds, optic nerve sheath distention, optic nerve tortuosity, globe flattening, retinal "cotton-wool spots", smaller changes in blood volume relative to increases in blood pressure (vascular compliance), intracranial pressure, increased CSF production, signs of elevated CSF pressure (pituitary concavity), and areas of constriction within veins of the brain.
3. It is expected that if an in-flight or postflight measure deviates from preflight baseline measures, the time required to recover to baseline (preflight values) will increase with the severity of the deviation.
The Ocular Health sessions will follow the current MRID requirements, but with increased frequency and will include an additional blood pressure measurement, transcranial Doppler, and vascular compliance testing. The following tests will be done pre-, in-, and post-flight:
• Visual Acuity: Near and far visual acuity will be tested for each eye independently with and without a corrective lens using an eye chart. The crewmember will be asked to stand 16 inches from the chart for the near-visual acuity test and 10 feet from the chart for the far-visual acuity test.
• Amsler Grid: Amsler grid testing is a measure of intact vision. It is used to assess visual changes in the central portion of the retina (the back of the eye). Amsler grid testing will be performed on both the right and left eye. The crewmember will be asked to sit 16 inches from the grid and focus on the dot in the center of the grid while slowly bringing the grid toward the uncovered eye until one of the red ovals disappears. Any changes to the appearance of the grid (wavy, blurred or missing lines) indicate a positive for this test.
• Contrast Sensitivity: This test checks for the ability to differentiate between light and dark (contrast) and is an important measure of visual function. Like a standard visual acuity chart, a contrast sensitivity chart consists of horizontal lines of capital letters. However, instead of the letters getting smaller on each successive line, the contrast of the letters (relative to the chart background) decreases with each line.
Intraocular Pressure and Blood Pressure: Intraocular pressure (IOP) is the fluid pressure of the aqueous humor inside the anterior chamber of the eye. Tonometry will be performed on the right and left eye using a commercial tonometer. In preparation for the measurement, 2 drops of Proparacaine or tetracaine will be given in each eye to anesthetize the eye. The operator will stabilize the subject’s head and gently tap the tonometer tip to the clear surface of the open eye directly over the pupil to obtain the measurement. At least one operator per increment must be trained to collect data. Prior to data collection, the operator will practice on the "eye simulator" to establish operator precision and accuracy. Tonometry cannot be effectively performed on oneself using the tonopen tonometer; therefore, if the operator also participates as a subject, a second operator must be trained. Immediately prior to tonometry, a blood pressure measurement will be obtained after 5 minutes of rest. After completing tonometry, an 8-hour rest is required prior to performing any other ocular test (overnight preferred).
Ocular Ultrasound: Ocular ultrasound will be used to identify changes in globe morphology, including flattening of the posterior globe, and document optic nerve sheath diameter (ONSD), optic nerve sheath tortuosity, globe axial measurements, and choroidal engorgement. Subjects will be seated (pre and postflight) or restrained (in-flight) during testing. A sonographer or trained crewmember will position the ultrasound probe with water over the closed eyelid and collect the ultrasound images. In-flight data collection will be assisted by remote guidance to ensure proper positioning and data collection.
Fundoscopy: Direct fundoscopy will be performed on the right and left eye to obtain images of the retinal surface. Subjects will receive this exam as part of their preflight, in-flight and postflight ophthalmological assessment. Since dilation is required for fundoscopy testing, sessions will be scheduled around in-flight piloting, EVA and docking activities. All in-flight exams will be remotely guided. Still images and short cine clips will be recorded. Up to four additional examinations will be conducted postflight if abnormalities of the fundus persist.
Optical Coherence Tomography and A-Scan (Note that A-Scan is also referred to as Optical Biometry): Optical coherence tomography (OCT) is a diagnostic imaging technique that is based on analysis of the reflection of low coherence radiation from the tissue under examination. It involves measurements of retinal thickness, volume, and retinal nerve fiber layer (RNFL) thickness using a method of quantitative cross sectional analysis. The OCT software is able to identify and "trace" two key layers of the retina, the nerve fiber layer and the retinal pigment epithelium. OCT is conducted preflight, in-flight, and postflight to detect subtle changes in the RNFL of the optic nerve head. The OCT scans are performed with the subject placing his or her chin on a chin rest while the device performs a scan of the eyes.
Vascular Compliance: Vascular compliance will be calculated by dividing a subjects stroke volume derived from echocardiographic measurement, by their pulse pressure, the difference between systolic and diastolic blood pressure measured at the brachial artery. Pre- and post-flight measurements will be made in both the supine and seated position, each preceded by 5 min of rest.
Transcranial Doppler (TCD): Pre and post-flight testing will take place following the vascular compliance (cardiac ultrasound) session. During this test, expired CO2 will be measured via a nasal prong. Continuous blood pressure will be monitored throughout the TCD session using a Finapress finger-tip monitor. The subject will be secured to a tilt table while lying supine (horizontally on the back). After five minutes of quiet rest, TCD recordings will be acquired for five minutes in each of four experimental positions, 90º (standing), 0 º (supine), 15º Head Down Tilt (HDT), and 25º HDT. After each experimental condition, the subject will be returned to the baseline horizontal position for 5 minutes prior to the next experimental condition. In-flight testing will be the same, except that the TCD recording will be made in only one position.
Additionally, the following tests will occur pre- and post-flight only:
Refraction Testing: Refraction is a procedure used to measure the refractive status of the eyes (i.e., to obtain a prescription for eyeglasses). This is accomplished by having the subject look through a phoropter and focus on an eye chart 20 feet away (manifest refraction). A more accurate measure of refractive error, called cycloplegic refraction, is obtained by administering eye drops to the subject to temporarily relax the focusing muscles of the eyes.
Threshold Visual Field Testing: This is an eye examination that can detect dysfunction in the central and peripheral vision. The subject is asked to look at a central spot on a screen (e.g., laptop computer) and to press a button or click a mouse each time a "light flicker" appears or a line on the screen is seen to move.
Pupil Reflexes: This test assesses the reaction of pupil size in response to light which is a test of the integrity of the neurological functions of the eye. The test operator will shine a bright light (e.g., penlight) in front of the subject's eye and watch for the pupil reaction.
Extraocular Muscle Balance: A moving target (e.g., pen) is used to track eye movements for assessing extraocular muscle function and integrity.
Magnetic Resonance Imaging (MRI): Pre and postflight magnetic resonance imaging (MRI) will be performed on all ISS crew. Several key parameters indicative of elevated intracranial pressure and its effects on ocular structures are measured during MRI scanning. Some of these measurements are similar to those obtained during on-orbit ultrasound which allow for comparison. Globe flattening, ONSD, ON tortuosity, optic nerve-to-sheath ratio, increased CSF production, signs of elevated CSF pressure (pituitary concavity), and areas of constriction within the veins of the brain are assessed with MRI.
Slit Lamp Biomicroscopy and High Resolution Retinal Photography: Slit lamp biomicroscopy and high resolution retinal photography are performed to evaluate and document any changes in eye structures.
VIIP 1 - We do not know the etiological mechanisms and contributing risk factors for ocular structural and functional changes seen in-flight and postflight.
By systematically measuring visual, vascular and central nervous system changes over the course of this experiment, a database could be developed to inform future in-flight research protocols, identify mechanisms, develop countermeasures, and direct clinical monitoring and clinical practice guidelines. If the conditions of microgravity are wholly or partially responsible, future exploration missions that are up to five times longer in duration than current ISS increments could be impacted
The information obtained from this spaceflight experiment may be relevant for patients suffering from eye diseases such as glaucoma, and diseases of the brain, for example, hydrocephalus and idiopathic intracranial hypertension.
A total of 12 subjects are required for this investigation. In-flight sessions are planned at FD10, FD30, FD60, FD90, FD120 and R-30 for a mission duration of six months and FD10, 30, 90, 150, 210, 270, and R-30 for a mission duration of one year. Tolerance for each test session is ±7 days, with at least 14 days between the last test of one FD session and the first test of the next FD session. All activities associated with the session required on a given FD may occur within a 5 day window. Both an operator and a subject are required for the ultrasound scans, fundoscopy, tonometry, OCT, and blood pressure, along with real-time video downlink to enable remote guidance by ground experts.
In-flight measures will be taken on Flight Days 10, 30, 60, 90, and 120 as well as 30 days prior to return for a mission duration of six months and on FD10, 30, 90, 150, 210, 270, and R-30 for a mission duration of one year. At each session the following tests will be performed: questionnaire, fundoscopy, OCT, visual acuity, Amsler grid, contrast sensitivity, tonometry with blood pressure, ocular ultrasound, cardiac ultrasound and transcranial Doppler imaging with blood pressure measurement. At Flight day 30 and 30-days prior to return, the questionnaire, ocular ultrasound, fundoscopy, OCT, visual acuity, Amsler grid, contrast sensitivity, and tonometry measurements will be obtained via data sharing with medical operations. The same measures will be obtained via data sharing on FD150 and FD210 for yearlong mission crewmembers. At FD90 for all crew and FD270 for yearlong mission crewmembers, visual acuity, questionnaire, Amsler grid, and contrast sensitivity will also be obtained via data sharing with medical operations.
Ground Based Results Publications
Marshall-Bowman K, Barratt MR, Gibson CR. Ophthalmic Changes and Increased Intracranial Pressure Associated with Long Duration Spaceflight: An Emerging Understanding. Acta Astronautica. 2013; epub.
NASA Image: ISS033E018532 - Japan Aerospace Exploration Agency (JAXA) astronaut Akihiko Hoshide,Expedition 33 flight engineer,prepares to perform ultrasound eye imaging in the Columbus laboratory of the International Space Station. This is part of the HMS (Health Maintenance System) Tonometry payload.
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