S EPTEMBER 2014, N O 11
ISOPTWPO Today
Sunita L. Williams (Captain, United States Navy),NASA Astronaut She received her commission as an Ensign in the United States Navy from the United States Naval Academy in May 1987. After a six-month temporary assignment at the Naval Coastal System Command, she received her designation as a Basic Diving Officer and then reported to Naval Aviation Training Command. She was designated a Naval Aviator in July 1989. She then reported to Helicopter Combat Support Squadron 3 for initial H46, Seaknight, training. Upon completion of this training, she was assigned to Helicopter Combat Support Squadron 8 in Norfolk, Virginia, and made overseas deployments to the Mediterranean, Red Sea and the Persian Gulf in support of Desert Shield and Operation Provide Comfort. In September 1992, she was the Officer-in-Charge of an H-46 detachment sent to Miami, Florida for Hurricane Andrew Relief Operations onboard USS Sylvania. Williams was selected for United States Naval Test Pilot School and began the course in January 1993. After graduation in December 1993, she was assigned to the Rotary Wing Aircraft Test Directorate as an H-46 Project Officer, and V-22 Chase Pilot in the T-2. While there, she was also assigned as the squadron Safety Officer and flew test flights in the SH-60B/F, UH-1, AH-1W, SH-2, VH-3, H-46, CH-53 and the H-57. In December 1995, she went back to the Naval Test Pilot School as an Instructor in the Rotary Wing Department and the school’s Safety Officer where she flew the UH-60, OH-6 and the OH-58. From there, she was assigned to the USS Saipan (LHA-2), Norfolk, Virginia, as the Aircraft Handler and the Assistant Air Boss. Williams was deployed onboard USS Saipan when she was selected for the astronaut program. Selected by NASA in June 1998, she reported for training in August 1998.Following a period of training and evaluation, Williams worked in Moscow with the Russian Space Agency on the Russian contribution to the space station and with the first Expedition Crew. Following the return of Expedition 1, Williams worked within the Robotics branch on the station’s Robotic Arm and the follow-on Special Purpose Dexterous Manipulator. As a NEEMO2 crewmember, she lived underwater in the Aquarius habitat for 9 days. After her first flight, she served as Deputy Chief of the Astronaut Office. She then supported a long duration mission as Flight Engineer for Expedition 32 and International Space Station Commander for Expedition 33. Williams has spent a total of 322 days in space on two missions; she ranks sixth on the all-time U.S. endurance list and second all-time for a female. With 50 hours 40 minutes, she also holds the record total cumulative spacewalk time by a female astronaut. — Image Credit:NASA
Human Space Flight Edition
Risk of Microgravity-Induced Visual Impairment/Intracranial Pressure (ICP) In spaceflight or a reduced-gravity environment, bodily fluids shift to the upper extremities of the body. The pressure inside the eye, or intraocular pressure, changes significantly. A significant number of astronauts report changes in visual acuity during orbital flight. To date this remains of unknown etiology. 50% of long- duration (ISS) mission astronauts report a subjective degradation in vision, primarily increasing farsightedness In the postflight time period, some individuals have experienced transient changes while others have experienced changes that are persisting with varying degrees of severity. While the underlying etiology of these changes is unknown at this time, the NASA medical community suspects that the microgravity-induced cephaladfluid shift and commensurate changes in physiology play a significant role. 15 U.S. ISS long-duration spaceflight astronauts have developed some or all of the following findings: • Hyperopic shift • Choroidal folds • Cotton wool spots • Optic Nerve Sheath Distention • Globe flattening • Edema of the Optic disc (papilledema) The Medical Requirements Integration Documents (MRID), contained herein, reflect the MR documented in the Astronaut Medical Evaluation Requirements Document (AMERD), JSC 24834, the ISS Medical Operations Requirements Document (ISS MORD), SSP 50260, and the Shuttle Medical Operations Requirements Document (MORD) JSC 13956. Changes to MR are approved by the Space Medicine Configuration Control Board (SMCCB) for both the Shuttle and ISS programs and by the Multilateral Medical Operations Panel (MMOP) for ISS. MR014S Eye Examinations
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Human Space Flight Edition
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Human Space Flight Edition
Annual Medical Examinations of Astronauts
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Human Space Flight Edition
There are limited pre and postflight measures to define the risk and even less in-flight data is available. These data show that there is a subset of crewmembers that experience visual performance decrements, cotton-wool spot formation, choroidal fold development, optic-disc edema, optic nerve sheath distention, and/or posterior globe flattening with varying degrees of severity and permanence. These changes define the visual impairment/intracranial pressure (VIIP) syndrome. NASA has determined that the first documented case of a U.S. astronaut affected by the VIIP syndrome occurred in an astronaut during a long-duration International Space Station (ISS) mission. The astronaut noticed a marked decrease in near-visual acuity throughout the mission. This individual.s postflight fundoscopic examination and fluorescence angiography revealed choroidal folds inferior to the optic disc and a cotton-wool spot in the right eye, with no evidence of optic-disc edema in either eye. The left eye examination was normal. The acquired choroidal folds gradually improved but were still present 3 years postflight. Brain MRI, lumbar puncture, and OCT were not performed preflight or postflight on this astronaut. Additional cases of altered visual acuity have been reported since, and one case has included the report of a scotoma (visual field defect), which resulted in the astronaut having to tilt his head 15 degrees to view instruments and procedures. These visual symptoms persisted for over 12 months after flight. This type of functional deficit is not only of concern to the individual, but is of concern to the mission and the ISS program managers. A postflight survey of approximately 300 astronauts, some of whom were repeat flyers, revealed that vision changes were commonly observed during and after long-duration space missions.After approximately 6 months of continuous orbital flight, 7 astronauts (all male; age 50.2 Âą 4.2 years) were documented to have findings as summarized in Table 1.
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Human Space Flight Edition
Table 2 is a summary of data from postflight questionnaires completed by approximately 300 astronauts after their short- and long-duration space missions. Approximately 23% of the short-duration and 48% of the longduration mission astronauts complained of near vision difficulties.
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Human Space Flight Edition Case 1 This astronaut’s preflight manifest refraction at 90 days before launch was: right eye, -1.50 sphere and left eye, -2.25 −0.25 × 135, with a +1.50 add. He was correctable to 20/20 in each eye and his dilated eye examination and fundus photos were normal. The only medication he used was promethazine for space adaptation syndrome. He noticed a marked decrease in near visual acuity starting about 6 weeks into the mission that persisted without progression for the remainder of the flight. At no time did he report headaches, transient visual obscurations, pulsatile tinnitus, or diplopia. Carbon dioxide levels were at normal operating levels < 5 mmHg during the entire mission. Oxygen levels were also normal at 160 to 170 mmHg (21%- 23%), the cabin pressure was steady at 735 to 765 mmHg, and there were no toxic fume exposures. Nineteen days after return to Earth, his visual acuity was correctable to 20/20 in both eyes with a manifest refraction of -1.25 to 0.25 × 005 in the right eye and -2.50 to 0.25 × 160 in the left, with a +2.00 add. He never at any time experienced losses in subjective best-corrected visual acuity, stereopsis, or color vision.His fundus examination revealed choroidal folds inferior to the optic disc (right eye) and a single cotton wool spot (CWS) in the inferior arcade. The acquired choroidal folds gradually improved, but were still present in fundus photographs taken 3 years postflight. The left eye examination was normal. There was no documented evidence of optic disc edema in either eye. Brain MRI, lumbar puncture (LP), and OCT were not performed preflight or postflight on this astronaut. It should be noted that choroidal folds are still present (right eye only) on OCT performed >5 years postflight. Case 2 This astronaut’s manifest refraction 120 days before the mission was +0.75 sphere on the right and +0.75 −0.25×165 on the left; his visual acuity was correctable in each eye to 20/15. He had a +2.25 bifocal add in both lenses. His dilated fundus examination was normal and documented with preflight fundus photos. During the mission, he took a multivitamin daily, potassium citrate (part of an experiment), and zolpidem occasionally for sleep induction.During the first 2 months in orbit, he had no visual complaints and could see the Earth clearly without glasses. Approximately 3 months into the mission, he noted that he could now only see the Earth clearly while looking through the lower portion of his progressive reading glasses. This change persisted for the remainder of the mission without noticeable improvement or progression. He complained of no transient visual obscurations, headaches, diplopia, pulsatile tinnitus, or vision changes during eye movement. Carbon dioxide, cabin pressure, and oxygen were at normal operating levels during the mission, and he was not exposed to any toxic substances. Upon return to Earth, the vision disturbances observed during microgravity continued. Twenty-one days after the mission, his visual acuity was correctable to 20/20 with a manifest refraction of +2.00 sphere on the right and +2.00 −0.50 × 140 on the left. Over the next several months, he noted a gradual but incomplete improvement in vision. His refraction 232 days postflight was +1.50 sphere on the right and +1.50 −0.25 × 170 on the left. He never at any time experienced losses in subjective best-corrected visual acuity, stereopsis, or color vision. Twenty-one days after his return to Earth, a fundus examination was performed, which documented mild bilateral nasal optic disc edema (grade 1,Frisén scale), right greater than left, and choroidal folds. Fluorescein angiography confirmed the choroidal folds but showed no other abnormalities. Magnetic resonance angiography and magnetic resonance venogram were normal. The OCT confirmed the increased nerve fiber layer (NFL) thickening consistent with optic disc edema nasally and demonstrated a normal macula. An MRI of the brain and orbits with and without gadolinium contrast, performed 23 days after return, documented mildly dilated ON sheaths and flattening of the posterior globes bilaterally. A CWS was present in the left eye 1 and 1 half disc diameters inferior temporal to the disc and just inside the inferior arcades. Two months after return to Earth, a LP documented a borderline opening pressure of 22 cm H2 O with normal cerebral spinal fluid (CSF) composition. Case 3 Preflight cycloplegic refraction was -0.50 sphere in the right eye and -0.25 sphere in the left eye, and correctable in each eye to 20/15. His dilated eye examination and fundus photos were normal. His past medical history included mild systemic hypertension controlled with lisinopril (10 mg) and dyslipidemia, wellcontrolled on atorvastatin (10 mg). During the mission, he also took promethazine for 2 days to treat symptoms of space adaptation syndrome, and a multivitamin (Centrum Silver, Pfizer, New York, New York), but no additional vitamin A analogs. He reported no changes in visual acuity during the mission with no complaints of headaches, transient visual obscurations, diplopia, or pulsatile tinnitus. Carbon dioxide and oxygen levels were at acceptable levels during the mission, and he had no toxic exposures. No ocular issues were reported by the astronaut at landing. Three days after return to Earth, he was correctable to 20/20 both eyes with a cycloplegic refraction of plano in each eye. Fundus examination revealed bilateral, asymmetrical disc edema(right eye, grade 3; left eye, grade 1). There was no evidence of choroidal folds or CWS. A small hemorrhage was observed inferior to the optic disc in the right eye. At 10 days postlanding, an MRI of the brain and orbits was normal except for ON thickening in the right eye greater than the left eye.There
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Human Space Flight Edition was no posterior globe flattening. A magnetic resonance venogram showed no evidence for cerebral venous sinus thrombosis. On OCT, there was marked NFL thickening (right eye more than the left eye), consistent with optic disc edema.At 19 days after return to Earth, an LP documented a mildly elevated opening pressure of 21 cm H2 O with normal CSF composition. Case 4 Preflight eye examination revealed a cycloplegic refraction of -0.75 to 0.50 × 100 on the right and plano −0.50 × 090 on the left, correctable in each eye to 20/15. He had a reading add of +2.00 both eyes. His preflight dilated eye examination and fundus photos were normal. During the mission, he used a topical corticosteroid and oral ketoconazole for a facial rash and promethazine for 1 day to treat symptoms of space adaptation syndrome. During the mission, this astronaut took a 6-day tapering dose of methylprednisolone followed by prednisone 40 mg/d for 1 week to treat an allergic skin condition. Approximately 6 to 8 weeks into the mission, he reported a progressive decrease in near visual acuity in his right eye, followed by a mild, "vertical football" -shaped scotoma located 15 degree to 30 degree into his right temporal field of vision. The scotoma seemed to be fixed and translucent, and was stable for the remainder of the mission. He never complained of transient visual obscurations, headaches, diplopia, pulsatile tinnitus, or vision changes during eye movement. International Space Station (ISS) cabin pressure, carbon dioxide, and oxygen levels were reported to be at normal operating levels during the mission. During the mission, one of his fellow astronauts also complained of decreased near visual acuity(case 5). Five months into the mission, a video funduscopic imaging system was used to obtain retinal and ON images that were downlinked to NASA personnel for ophthalmologic consultation. These images allowed experts on the ground to diagnose mild optic disc edema in the right eye . The temporal location and shape of the reported scotoma was thought to be consistent with disc edema (i.e., enlarged blind spot). His vision changes persisted upon return to Earth. Ten days postflight, his visual acuity was correctable to 20/15 with a cycloplegic refraction of +0.75 to 0.50 × 105 on the right and to +0.75 to 0.75 × 090 on the left. He never experienced losses in subjective best-corrected acuity, color vision, or stereopsis. Fundus examination revealed mild, nasal disc edema (grade 1, Frisén scale) of the right eye with choroidal folds extending from the disc into the macula. On OCT, optic disc edema and choroidal folds were confirmed.An MRI of the brain and orbits performed 30 days postflight documented severely dilated ON sheaths (right greater than left), flattening of the posterior globes (right greater than left), and thickened tortuous ONs. An intracranial magnetic resonance venogram and magnetic resonance angiography subsequently obtained showed no abnormalities. Fifty-seven days after return to Earth, an LP documented an elevated opening pressure of 28.5 cm H2 O with normal CSF composition. Case 5 A preflight eye examination revealed a cycloplegic refraction of -5.75 to 1.25×010 on the right, and -5.00 to 1.50×180 on the left, correctable in each eye to 20/20. His reading add was +1.75 both eyes. Dilated eye examination and fundus photos were normal. During the mission, he took promethazine for a few days to treat symptoms of space adaptation syndrome. Three weeks after launch, he reported a moderate decrease in near visual acuity, right eye greater than left, which persisted for the remainder of the mission without change. He never complained of headaches, transient visual obscurations, diplopia, pulsatile tinnitus, or other vision changes. Carbon dioxide, oxygen, and ISS cabin pressure were at acceptable levels during the mission. One fellow crewmember complained of visual changes (case 4). Upon return to Earth, he noted persistence of the vision changes he observed in space. Postflight visual acuity was correctable to 20/20 both eyes with a manifest and cycloplegic refraction of -5.00 to 1.50 × 015 on the right and -4.75 to 1.75 × 170 on the left and a reading add of +2.25 both eyes. He never experienced losses in subjective bestcorrected acuity, color vision, or stereopsis. His fundus examination was normal with no evidence of disc edema or choroidal folds. However, MRI of the brain and orbits, performed 8 days after return, documented bilateral posterior globe flattening, distended ON sheaths, and tortuous ONs. The ONs were not thickened. On OCT, significant NFL thickening in the right eye was shown relative to preflight values and a normal macula. An LP was not performed. Case 6 Preflight eye examination documented a cycloplegic refraction of +0.25 sphere on the right and +0.25 to 0.50 × 152 on the left, correctable in each eye to 20/15 with a reading add of +1.25. His dilated eye examination and fundus photos were normal. During the mission he took promethazine for 1 to 2 days to treat symptoms of space adaptation syndrome. He reported no significant changes in visual acuity during the mission and never complained of transient visual obscurations, diplopia, pulsatile tinnitus, or other vision changes. Carbon dioxide, oxygen, and cabin pressure levels were reported to be within acceptable levels throughout the mission. He was not exposed to any toxic substances. After return to Earth, he noticed that his far vision was clearer through his reading glasses. Twenty-one days after his return to Earth, his visual acuity was correctable to 20/20 both eyes with a cycloplegic refraction of +2.00 to 0.50 × 028 on the right, and +1.00 sphere on the left. A fundus examination documented mild (grade 1) nasal
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Human Space Flight Edition optic disc edema in the right eye only . There was no evidence of disc edema in the left eye. An MRI of the brain and orbits, performed 46 days after return, revealed bilateral flattening of the posterior globe, right greater than left, and a mildly distended right ON sheath. Forty-eight days after return to Earth, his cycloplegic refraction was +1.50 sphere on the right and +0.75 sphere on the left. He never experienced losses in subjective best-corrected acuity, color vision, or stereopsis. Fundus examination and OCT performed at this time documented mild disc edema (right eye, grade 1) and a CWS in the left eye 2 disc diameters superior temporal to the disc, just inside the superior arcade. Although no choroidal folds were visible by ophthalmoscopy in either eye, mild choroidal folds were noted in the right eye by OCT. An LP was not performed. Case 7 Preflight cycloplegic refraction was +1.25 sphere both eyes, correctable in each eye to 20/15 with a reading add of +1.75. His preflight dilated eye examination and fundus photos were normal. During the mission, he took promethazine 25 mg by mouth on day 1 of the mission and 12.5 mg on day 2 to treat symptoms of space adaptation syndrome. While in orbit, he took atorvastatin 40 mg every day, vitamin D 50 000 IU/month, and 800 mg ibuprofen as needed. Approximately 2 months into the mission he reported a progressive decrease in his near and far acuity in both eyes, which persisted for the remainder of the mission. At approximately 3 to 4 months into the 6-month mission, he noticed that his normal "Earth" prescription progressive glasses were no longer strong enough for near tasks at which time he began using his stronger "Space Anticipation Glasses" (+1.25 D more plus). He never complained of transient visual obscurations, headaches, diplopia, pulsatile tinnitus, or vision changes during eye movement. The ISS cabin pressure, carbon dioxide, and oxygen levels were reported to be at normal operating levels during the mission. He was not exposed to any toxic substances. Three days after his return to Earth, his visual acuity was correctable to 20/20 both eyes with a cycloplegic refraction of +2.75 sphere on the right, and +2.50 sphere on the left. He never experienced losses in subjective best-corrected acuity, color vision, or stereopsis. A fundus examination revealed mild bilateral optic disc edema (grade 1), and choroidal folds . On OCT, optic disc edema and chorioretinal folds were confirmed . An MRI of the brain and orbits performed 6 days postflight documented bilateral flattening of the posterior globes, distended ON sheaths, and papilledema. Twelve days after return to Earth, LP documented an elevated opening pressure of 28 cm H2 O with normal CSF composition. A mild degradation in uncorrected near visual acuity and a mild hyperopic shift was documented on this astronaut after a previous short-duration Space Shuttle mission several years before his long-duration mission. His post-Space Shuttle, short-duration flight eye examination was normal with no evidence of disc edema or choroidal folds. At that time, MRI and OCT were not performed postflight. His preflight long-duration OCT raster scans showed what could be evidence of residual choroidal folds from his prior short-duration mission. CASE DEFINITION/CLINICAL PRACTICE GUIDELINES Space Medicine Division developed clinical practice guidelines for the treatment of affected astronauts. According to the guidelines, all long-duration astronauts that have demonstrated postflight refractive changes should be considered a suspected case; cases could be further differentiated by definitive imaging studies establishing the postflight presence of optic-disc edema, increased ONSD, and altered OCT findings. The results of the imaging studies are divided into five classes that determine the follow-up testing/monitoring that is required. The definition of the classes and Frisén scale used for optic-disc edema diagnosis are listed below. • Class 0 – < .50 diopter cycloplegic refractive change – No evidence of optic-disc edema, nerve sheath distention, choroidal folds, globe flattening, scotoma, or cotton-wool spots compared to baseline • Class 1 (repeat OCT and visual acuity in 6 weeks) – Refractive changes ≥ .50 diopter cycloplegic refractive change and/or cotton-wool spot – No evidence of optic-disc edema, nerve sheath distention, choroidal folds, globe flattening, scotoma, compared to baseline – CSF opening pressure (if measured) ≤ 25 cm H2 O • Class 2 (repeat OCT, cycloplegic refraction, fundus examination and threshold visual field every 4 to 6 weeks × 6 months, repeat MRI in 6 months) ISOPTWPO Today c International Space Agency(ISA)
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Human Space Flight Edition – ≥ .50 diopter cycloplegic refractive changes or cotton-wool spot – Choroidal folds and/or ONS distension and/or globe flattening and/or scotoma – No evidence of optic-disc edema – CSF opening pressure ≤ 25 cm H2 O (if measured) • Class 3 (repeat OCT, cycloplegic refraction, fundus examination and threshold visual field every 4 to 6 weeks × 6 months, repeat MRI in 6 months) – ≥ .50 diopter cycloplegic refractive changes and/or cotton-wool spot – Optic nerve sheath distension, and/or globe flattening and/or choroidal folds and/or scotoma – Optic-disc edema of Grade 0-2 – CSF opening pressure ≤ 25 cm H2 O • Class 4 (institute treatment protocol as per Clinical Practice Guideline) – ≥ .50 diopter cycloplegic refractive changes and/or cotton-wool spot – Optic nerve sheath distension, and/or globe flattening and/or choroidal folds and/or scotoma – Optic-disc edema Grade 2 or above – Presenting symptoms of new headache, pulsatile tinnitus and/or transient visual obscurations – CSF opening pressure > 25 cm H2 O
Optic-disc edema will be graded based on the Frisén Scale as below: • Stage 0 - Normal Optic Disc Blurring of nasal, superior and inferior poles in inverse proportion to disc diameter. Radial nerve fiber layer (NFL) without NFL tortuosity. Rare obscuration of a major blood vessel, usually on the upper pole. • Stage 1 - Very Early Optic-disc edema Obscuration of the nasal border of the disc. No elevation of the disc borders. Disruption of the normal radial NFL arrangement with grayish opacity accentuating nerve fiber layer bundles. Normal temporal disc margin. Subtle grayish halo with temporal gap (best seen with indirect ophthalmoscopy). Concentric or radial retrochoroidal folds. • Stage 2 - Early Optic-disc edema Obscuration of all borders. Elevation of the nasal border. Complete peripapillary halo. • Stage 3 - Moderate Optic-disc edema Obscurations of all borders. Increased diameter of ONH. Obscuration of one or more segments of major blood vessels leaving the disc. Peripapillary halo-irregular outer fringe with finger-like extensions. • Stage 4 - Marked Optic-disc edema Elevation of the entire nerve head. Obscuration of all borders. Peripapillary halo. Total obscuration on the disc of a segment of a major blood vessel. • Stage 5 - Severe Optic-disc edema Dome-shaped protrusions representing anterior expansion of the ONH. Peripapillary halo is narrow and smoothly demarcated. Total obscuration of a segment of a major blood vessel may or may not be present. Obliteration of the optic cup.
MRI Findings Associated with Microgravity • Optic nerve sheath distension
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Human Space Flight Edition • Optic disc edema • Posterior Globe Flattening • Tortuosity of the optic nerve sheath • Moderate Concavity of the pituitary gland with posterior displacement of the stalk
MR imaging of the orbits and brain was performed in 27 consecutive astronauts (group 1; mean age ± standard deviation, 48.4 years ± 4.5) with a history of microgravity exposure. All group 1 astronauts had previous exposure to microgravity and, thus, control data were not available for comparison. The first astronaut was imaged for evaluation of acute visual acuity degradation that occurred during a mission and that was accompanied by choroidal folds. All subsequent studies were performed for postflight assessment irrespective of timing to last mission or reference to specific symptoms. Eight astronauts (group 2; mean age, 47.8 years ± 4.0) underwent a repeat study after an additional mission in space. The total flight days in microgravity averaged 108 days ± 100 for group 1 and 130 days ± 121 for group 2. The subsequent mission in group 2 averaged an additional 39 days ± 70 of microgravity exposure. The mean ONSDs at 3, 4, and 5 mm posterior to the VRI for group 1 are with a maximum value at 3 mm. Excellent reproducibility was demonstrated for ONSD measurements for both intra- and interobserver data sets. For the eight astronauts in group 2, the mean ONSD at 4 mm posterior to the VRI was 6.65 mm ± 1.42 before space flight and did not significantly differ after the mission, measuring 6.66 mm ± 1.72 (P = .97, paired t test). In group 1, 20 astronauts with unremarkable globes had a mean ONSD of 5.8 mm ± 0.6 at 4 mm posterior to the VRI; this was significantly different (P= .01, Mann-Whitney test) from that in seven astronauts with posterior globe flattening (mean ONSD, 7.2 mm ± 1.5). Twenty-three astronauts with unremarkable optic nerve sheaths had a mean ONSD of 5.9 mm ± 0.8 at 4 mm posterior to the VRI, which was significantly different from that in four astronauts with optic nerve sheath kinking (mean ONSD, 7.5 mm ± 1.1; P = .03,Mann-Whitney test). The mean retrolaminar OND was 3.0 mm ± 0.5 (right eye) and 3.0 mm ± 0.4 (left eye) at 3 mm posterior to the VRI. The retrolaminar OND (right eye) was plotted relative to ONSD at 4 mm posterior to the VRI and demonstrated a linear increase with increasing ONSD (r = 0.797, Pearson correlation). The mean time to MR imaging was 606 days ± 822 for group 1 and 6.5 days ± 9.6 for group 2. Eighteen group 1 astronauts underwent imaging more than 100 days after flight, and some showed persistent evidence of posterior globe flattening (n = 3), optic nerve sheath kinking (n = 1), optic disc protrusion (n = 1), ONSD of at least 5.9 mm at 4 mm posterior to the VRI (n = 9), and moderate or greater concavity of the pituitary gland with posterior stalk displacement (n = 1). A central area of T2 hyperintensity in the optic nerve was found in 26 of the 27 astronauts (96%) with the T2weighted 3D fast spin-echo sequence and in 14 of 16 astronauts (88%) with the coronal short tau inversion-recovery sequence. Sixteen examinations in group 1 astronauts had sufficient image quality to quantify the optic nerve at mid orbit. In 12 astronauts with normal optic sheath morphology, the mean mid orbit OND was 2.2 mm ± 0.2 and the mean diameter of the central area of T2 hyperintensity was 0.9 mm ± 0.1. In four astronauts with an optic nerve sheath kink, the mean mid orbit OND was 2.8 mm ± 0.4 and the mean diameter of the central area of T2 hyperintensity was 1.4 mm ± 0.5. There were significant differences in the OND (P = .01, Mann-Whitney test) and the diameter of the central area of T2 hyperintensity (P = .05, Mann-Whitney test) between groups. A rapid transition in the diameter of the central area of T2 hyperintensity was clearly identified at the level of the kink in one severe case . There was no evidence of vasogenic edema, hydrocephalus, mass lesions, or central venous thrombosis. Three astronauts underwent a lumbar puncture on the basis of clinical concerns, yielding CSF pressures of 23, 28, and 29 cm H2 O at 12, 453, and 57 days after flight, respectively. All three astronauts were noted to have posterior globe flattening and optic disc protrusion. Prospective Observational Study of Ocular Health in ISS Crews (Ocular Health) 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 ISOPTWPO Today c International Space Agency(ISA)
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Human Space Flight Edition 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,
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Human Space Flight Edition 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, 90 degree (standing), 0 degree (supine), 15 degree Head Down Tilt (HDT), and 25 degree 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. • 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 nerveto-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.
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Human Space Flight Edition Reference: 1.Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, Fogarty J, Tarver WJ, Dervay JP, Hamilton DR, Sargsyan A, Phillips JL, Tran D, Lipsky W, Choi J, Stern C, Kuyumjian R, Polk JD. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in Astronauts after long-duration space flight. Ophthalmology, 2011; 118(10): 2058-69. 2.Frisen L. Swelling of the optic nerve head: a staging scheme. J Neurol Neurosurg Psychiatry, 1982; 45(1): 13-8. 3.Marshall-Bowman K, Barratt MR, Gibson CR. Ophthalmic Changes and Increased Intracranial Pressure Associated with Long Duration Spaceflight: An Emerging Understanding. Acta Astronautica. 2013. 4.Evidence Report,Risk of Spaceflight-Induced Intracranial Hypertension and Vision Alterations,NASA. Ë? 5.The Visual Impairment Intracranial Pressure Summit Report,NASA/TPU2011-216160. 6.MEDICAL REQUIREMENTS INTEGRATION DOCUMENTS (MRID) BOOK,JSC 28913. 7.MR089S Annual Medical Examinations,MR089S,SM-FI-125-1-R1. 8.MR014S Eye Examinations,SLSDCR-SMCCB-10-043-R2. 9.Karina Marshall-Bowman,Increased Intracranial Pressure and Visual Impairment Associated with Long-Duration Spaceflight,Project Report,August, 2011. 10.RL Cromwell, SB Zanello, PO Yarbough, G Taibbi, G Vizzeri,COMPARISON OF OCULAR OUTCOMES IN TWO 14DAY BED REST STUDIES.
11.Larry A. Kramer, Ashot E. Sargsyan, Khader M. Hasan, James D. Polk, and Douglas R. Hamilton,Orbital and Intracranial Effects of Microgravity: Findings at 3-T MR Imaging,Radiology 2012 263:3, 819-827.
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ISOPTWPO The ISOPTWPO is International Space Flight & Operations - Personnel Recruitment, Training, Welfare, Protocol Programs Office (International Space Academy). It is a division of the ISA organization. Mr. Martin Cabaniss is director and Mr. Abhishek Kumar Sinha is Assistant Director of ISOPTWPO. Ad Astra ! To The Stars! In Peace For All Mankind ! Mr. Rick R. Dobson, Jr.(Veteran U.S Navy) â&#x20AC;&#x201D; International Space Agency (ISA)
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