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Spaceflight-associated neuro-ocular syndrome (SANS), previously known as ''Spaceflight-induced
visual impairment Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment� ...
'', is hypothesized to be a result of increased
intracranial pressure Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury ( mmHg) and at rest, is normally 7–15 mmHg for a supine adult. ...
. The study of visual changes and intracranial pressure (ICP) in astronauts on long-duration flights is a relatively recent topic of interest to Space Medicine professionals. Although reported signs and symptoms have not appeared to be severe enough to cause blindness in the near term, long term consequences of chronically elevated intracranial pressure is unknown. NASA has reported that fifteen long-duration male astronauts (45–55 years of age) have experienced confirmed visual and anatomical changes during or after long-duration flights. Optic disc edema, globe flattening, choroidal folds, hyperopic shifts and an increased intracranial pressure have been documented in these astronauts. Some individuals experienced transient changes post-flight while others have reported persistent changes with varying degrees of severity. Although the exact cause is not known, it is suspected that microgravity-induced cephalad fluid shift and comparable physiological changes play a significant role in these changes. Other contributing factors may include pockets of increased CO2 and an increase in sodium intake. It seems unlikely that resistive or aerobic exercise are contributing factors, but they may be potential countermeasures to reduce intraocular pressure (IOP) or intracranial pressure (ICP) in-flight.


Causes and current studies

Although a definitive cause (or set of causes) for the symptoms outlined in the Existing Long-Duration Flight Occurrences section is unknown, it is thought that venous congestion in the brain brought about by cephalad-fluid shifts may be a unifying pathologic mechanism. Additionally, a recent study reports changes in CSF hydrodynamics and increased diffusivity around the optic nerve under simulated microgravity conditions which may contribute to ocular changes in spaceflight. As part of the effort to elucidate the cause(s), NASA has initiated an enhanced occupational monitoring program for all mission astronauts with special attention to signs and symptoms related to ICP. Similar findings have been reported among Russian Cosmonauts who flew long-duration missions on MIR. The findings were published by Mayasnikov and Stepanova in 2008. Animal research from the Russian Bion-M1 mission indicates duress of the cerebral arteries may induce reduced blood flow, thereby contributing to impaired vision. On 2 November 2017, scientists reported that significant changes in the position and structure of the brain have been found in
astronaut An astronaut (from the Ancient Greek (), meaning 'star', and (), meaning 'sailor') is a person trained, equipped, and deployed by a human spaceflight program to serve as a commander or crew member aboard a spacecraft. Although generally ...
s who have taken trips in space, based on MRI studies. Astronauts who took longer space trips were associated with greater brain changes.


CO2

Carbon dioxide (CO2) is a natural product of metabolism. People typically exhale around 200mL of CO2 per minute at rest and over 4.0 L at peak exercise levels. In a closed environment, CO2 levels can quickly rise and can be expected to a certain degree in an environment such as the ISS. Nominal CO2 concentrations on Earth are approximately 0.23 mmHg while nominal CO2 levels aboard the ISS are up to 20 times that at 2.3 to 5.3 mmHg. Those astronauts who experienced VIIP symptoms were not exposed to CO2 levels in excess of 5 mmHg. Ventilation and heart rate increase as CO2 rise.
Hypercapnia Hypercapnia (from the Greek ''hyper'' = "above" or "too much" and ''kapnos'' = "smoke"), also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous pro ...
also stimulates
vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction ...
of cerebral blood vessels, increased cerebral blood flow and elevated ICP presumably leading to headache, visual disturbance and other central nervous system (CNS) symptoms. CO2 is a known potent vasodilator and an increase in cerebral perfusion pressure will increase the CSF fluid production by about 4%. Since air movement is reduced in microgravity, local pockets of increased CO2 concentrations may form. Without proper ventilation, CO2 concentrations ppCO2 could rise above 9mmHg within 10 minutes around a sleeping astronaut's mouth and chin. More data is needed to fully understand the individual and environmental factors that contribute to CO2-related symptoms in microgravity.


Sodium intake

A link between increased ICP and altered sodium and water retention was suggested by a report in which 77% of IIH patients had evidence of
peripheral edema Peripheral edema is edema (accumulation of fluid causing swelling) in tissues perfused by the peripheral vascular system, usually in the lower limbs. In the most dependent parts of the body (those hanging distally), it may be called dependent ed ...
and 80% with orthostatic retention of sodium and water. Impaired saline and water load excretions were noted in the upright position in IIH patients with orthostatic edema compared to lean and obese controls without IIH. However, the precise mechanisms linking orthostatic changes to IIH were not defined, and many IH patients do not have these sodium and water abnormalities. Astronauts are well known to have orthostatic intolerance upon reentry to gravity after long-duration spaceflight, and the dietary sodium on orbit is also known to be in excess of 5 grams per day in some cases. The Majority of the NASA cases did have high dietary sodium during their increment. The ISS program is working to decrease in-flight dietary sodium intake to less than 3 grams per day. Prepackaged foods for the International Space Station were originally high in sodium at 5300 mg/d. This amount has now been substantially reduced to 3000 mg/d as a result of NASA reformulation of over ninety foods as a conscious effort to reduce astronaut sodium intake.


Exercise

While exercise is used to maintain muscle, bone and cardiac health during spaceflight, its effects on ICP and IOP have yet to be determined. The effects of resistive exercise on the development of ICP remains controversial. An early investigation showed that the brief intrathoracic pressure increase during a
Valsalva maneuver The Valsalva maneuver is performed by a forceful attempt of exhalation against a closed airway, usually done by closing one's mouth and pinching one's nose shut while expelling air out as if blowing up a balloon. Variations of the maneuver can ...
resulted in an associated rise in ICP. Two other investigations using transcranial Doppler ultrasound techniques showed that resistive exercise without a Valsalva maneuver resulted in no change in peak systolic pressure or ICP. The effects of resistive exercise in IOP are less controversial. Several different studies have shown a significant increase in IOP during or immediately after resistive exercise. There is much more information available regarding
aerobic exercise Aerobic exercise (also known as endurance activities, cardio or cardio-respiratory exercise) is physical exercise of low to high intensity that depends primarily on the aerobic energy-generating process. "Aerobic" is defined as "relating to, inv ...
and ICP. The only known study to examine ICP during aerobic exercise by invasive means showed that ICP decreased in patients with intracranial hypertension and those with normal ICP. They suggested that because aerobic exercise is generally done without Valsalva maneuvers, it is unlikely that ICP will increase during exercise. Other studies show global brain blood flow increases 20–30% during the transition from rest to moderate exercise. More recent work has shown that an increase in exercise intensity up to 60% VO2max results in an increase in CBF, after which CBF decreases towards (and sometimes below) baseline values with increasing exercise intensity.


Biomarkers

Several biomarkers may be used for early VIIP Syndrome detection. The following biomarkers were suggested as potential candidates by the 2010 Visual Impairment Summit: *
albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...
*
aquaporin Aquaporins, also called water channels, are channel proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells, mainly facilitating transport of water between cells. The cell membranes of a ...
* atrial naturetic peptide * CRP/inflammation markers * immunoglobin G index *
insulin-like growth factor The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system (often referred to as the IGF " ...
s *
myelin basic protein Myelin basic protein (MBP) is a protein believed to be important in the process of myelination of nerves in the nervous system. The myelin sheath is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly ...
*
oligoclonal band Oligoclonal bands (OCBs) are bands of immunoglobulins that are seen when a patient's blood serum, or cerebrospinal fluid (CSF) is analyzed. They are used in the diagnosis of various neurological and blood diseases, especially in multiple sclerosis. ...
s *
platelet count Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ...
* S-100 *
somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coup ...
* tet-transactivator (TTA) *
vasopressin Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
Also,
gene expression profiling In the field of molecular biology, gene expression profiling is the measurement of the activity (the expression) of thousands of genes at once, to create a global picture of cellular function. These profiles can, for example, distinguish between c ...
,
epigenetic modifications Embryonic stem cells are capable of self-renewing and differentiating to the desired fate depending on their position in the body. Stem cell homeostasis is maintained through epigenetic mechanisms that are highly dynamic in regulating the chromati ...
, CO2 retaining variants,
single-nucleotide polymorphism In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
s and copy number variants should be expanded in order to better characterize the individual susceptibility to develop the VIIP syndrome. As the etiology of the symptoms is more clearly defined, the appropriate biomarkers will be evaluated.


One-carbon metabolism (homocysteine)

While the common theories regarding vision issues during flight focus on cardiovascular factors (fluid shift, intracranial hypertension, CO2 exposure, etc.), the difficulty comes in trying to explain how on any given mission, breathing the same air and exposed to the same microgravity, why some crewmembers have vision issues while others do not. Data identified as part of an ongoing nutrition experiment found biochemical evidence that the folate-dependent one-carbon metabolic pathway may be altered in those individuals who have vision issues. These data have been published and summarized by the ISS Program, and described in a journal sponsored pubcast. In brief: serum concentrations of metabolites of the
folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
, vitamin B-12 dependent one carbon metabolism pathway, specifically,
homocysteine Homocysteine is a non-proteinogenic α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. In the ...
,
cystathionine Cystathionine is an intermediate in the synthesis of cysteine. Cystathionine is produced by the transsulfuration pathway which converts homocysteine into cystathionine. Cystathionine is then used by the enzymes cystathionine gamma-lyase (CTH), ...
, 2-methylcitric acid, and
methylmalonic acid Methylmalonic acid (MMA) (conjugate base methylmalonate) is a dicarboxylic acid that is a ''C''-methylated derivative of malonate. The coenzyme A linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylmalon ...
were all significantly (P<0.001) higher (25–45%) in astronauts with ophthalmic changes than in those without such changes. These differences existed before, during, and after flight. Serum folate tended to be lower (P=0.06) in individuals with ophthalmic changes. Preflight serum concentrations of cystathionine and 2-methylcitric acid, and mean in-flight serum folate, were significantly (P<0.05) correlated with changes in refraction (postflight relative to preflight). Thus, data from the Nutrition SMO 016E provide evidence for an alternative hypothesis: that individuals with alterations in this metabolic pathway may be predisposed to anatomic and/or physiologic changes that render them susceptible to ophthalmologic damage during space flight. A follow-up project has been initiated (the "One Carbon" study) to follow up and clarify these preliminary findings.


Space obstructive syndrome

An anatomic cause of the microgravity related intracranial hypertension and visual disturbances has been proposed and is termed Space Obstructive Syndrome or SOS. This hypothesis has the possibility of linking the various symptoms and signs together through a common mechanism in a cascade phenomenon, and explaining the findings in one individual and not another due to specific anatomic variations in the structural placement of the internal jugular vein. This hypothesis was presented in May 2011 at the annual meeting of the Aerospace Medicine Association in Anchorage, Alaska, and was published in January, 2012. In 1G on earth, the main outflow of blood from the head is due to gravity, rather than a pumping or vacuum mechanism. In a standing position, the main outflow from the head is through the vertebral venous system because the
internal jugular veins The internal jugular vein is a paired jugular vein that collects blood from the brain and the superficial parts of the face and neck. This vein runs in the carotid sheath with the common carotid artery and vagus nerve. It begins in the posterio ...
, located primarily between the carotid artery and the
sternocleidomastoid muscle The sternocleidomastoid muscle is one of the largest and most superficial cervical muscles. The primary actions of the muscle are rotation of the head to the opposite side and flexion of the neck. The sternocleidomastoid is innervated by the access ...
are partially or completely occluded due to the pressure from these structures, and in a supine position, the main outflow is through the internal jugular veins as they have fallen laterally due to the weight of the contained blood, are no longer compressed and have greatly expanded in diameter, but the smaller vertebral system has lost the gravitational force for blood outflow. In microgravity, there is no gravity to pull the internal jugular veins out from the zone of compression (Wiener classification Zone I), and there is also no gravitational force to pull blood through the vertebral venous system. In microgravity, the cranial venous system has been put into minimal outflow and maximal obstruction. This then causes a cascade of cranial venous hypertension, which decreases CSF resorption from the
arachnoid granulations Arachnoid granulations (also arachnoid villi, and pacchionian granulations or bodies) are small protrusions of the arachnoid mater (the thin second layer covering the brain) into the outer membrane of the dura mater (the thick outer layer). They p ...
, leading to
intracranial hypertension Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 mmHg for a supine adult. Th ...
and
papilledema Papilledema or papilloedema is optic disc swelling that is caused by increased intracranial pressure due to any cause. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare. In ...
. The venous hypertension also contributes to the head swelling seen in photos of astronauts and the nasal and sinus congestion along with headache noted by many. There is also subsequent venous hypertension in the venous system of the eye which may contribute to the findings noted on ophthalmic exam and contributing to the visual disturbances noted. The astronauts affected by long term visual changes and prolonged intracranial hypertension have all been male, and SOS may explain this because in men, the sternocleidomastoid muscle is typically thicker than in women and may contribute to more compression. The reason that SOS does not occur in all individuals may be related to anatomic variations in the internal jugular vein. Ultrasound study has shown that in some individuals, the internal jugular vein is located in a more lateral position to Zone I compression, and therefore not as much compression will occur, allowing continued blood flow.


Current ICP and IOP measurement


ICP measurement

Intracranial pressure (ICP) needs to be directly measured before and after long duration flights to determine if microgravity causes the increased ICP. On the ground, lumbar puncture is the standard method of measuring cerebral spinal fluid pressure and ICP, but this carries additional risk in-flight. NASA is determining how to correlate ground-based MRI with inflight ultrasound and other methods of measuring ICP in space is currently being investigated. To date, NASA has measured intraocular pressure (IOP), visual acuity, cycloplegic refraction, Optical Coherence Tomography (OCT) and A-scan axial length changes in the eye before and after spaceflight.


Non-invasive ICP measurement

There are different approaches to non-invasive intracranial pressure measurement, which include ultrasound "time-of-flight" techniques, transcranial Doppler, methods based on acoustic properties of the cranial bones, EEG, MRI, tympanic membrane displacement, oto-acoustic emission, ophthalmodynamometry, ultrasound measurements of optic nerve sheath diameter, and Two-Depth Transorbital Doppler. Most of the approaches are "correlation based". Such approaches can not measure an absolute ICP value in mmHg or other pressure units because of the need for individual patient specific calibration. Calibration needs non-invasive "gold standard" ICP meter which does not exists. Non-invasive absolute intracranial pressure value meter, based on ultrasonic Two-Depth Transorbital Doppler technology, has been shown to be accurate and precise in clinical settings and prospective clinical studies. Analysis of the 171 simultaneous paired recordings of non-invasive ICP and the "gold standard" invasive CSF pressure on 110 neurological patients and TBI patients showed good accuracy for the non-invasive method as indicated by the low mean systematic error (0.12 mmHg; confidence level (CL) = 0.98). The method also showed high precision as indicated by the low standard deviation (SD) of the random errors (SD = 2.19 mmHg; CL = 0.98). This measurement method and technique (the only non-invasive ICP measurement technique which already received EU CE Mark approval) eliminates the main limiting problem of all other non-successful "correlation based" approaches to non-invasive ICP absolute value measurement – the need of calibration to the individual patient.


IOP measurement

Intraocular pressure (IOP) is determined by the production, circulation and drainage of ocular
aqueous humor The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the posteri ...
and is described by the equation:
::IOP =\frac +PV Where:
::F = aqueous fluid formation rate ::C = aqueous outflow rate ::PV = episcleral venous pressure In general populations IOP ranges between and 20 mmHg with an average of 15.5 mmHg, aqueous flow averages 2.9 μL/min in young healthy adults and 2.2 μL/min in octogenarians, and episcleral venous pressure ranges from 7 to 14 mmHg with 9 to 10 mmHg being typical.


Existing long-duration flight occurrences

The first U.S. case of visual changes observed on orbit was reported by a long-duration astronaut that noticed a marked decrease in near-visual acuity throughout his mission on board the
ISS The International Space Station (ISS) is the largest modular space station currently in low Earth orbit. It is a multinational collaborative project involving five participating space agencies: NASA (United States), Roscosmos (Russia), JAXA ( ...
, but at no time reported
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result of ...
s, transient visual obscurations, pulsatile tinnitus or
diplopia Diplopia is the simultaneous perception of two images of a single object that may be displaced horizontally or vertically in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often v ...
(double vision). His postflight fundus examination (Figure 1) revealed choroidal folds below the
optic disc The optic disc or optic nerve head is the point of exit for ganglion cell axons leaving the eye. Because there are no rods or cones overlying the optic disc, it corresponds to a small blind spot in each eye. The ganglion cell axons form th ...
and a single cotton-wool spot in the inferior arcade of the right eye. The acquired choroidal folds gradually improved, but were still present 3 year postflight. The left eye examination was normal. There was no documented evidence of optic-disc edema in either eye.
Brain MRI Magnetic resonance imaging of the brain uses magnetic resonance imaging (MRI) to produce high quality two-dimensional or three-dimensional images of the brain and brainstem as well as the cerebellum without the use of ionizing radiation (X-rays) o ...
,
lumbar puncture Lumbar puncture (LP), also known as a spinal tap, is a medical procedure in which a needle is inserted into the spinal canal, most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. The main reason for a lumbar puncture is to ...
, and OCT were not performed preflight or postflight on this astronaut. The second case of visual changes during long-duration spaceflight on board the ISS was reported approximately 3 months after launch when the astronaut noticed that he could now only see Earth clearly while looking through his reading glasses. The change continued for the remainder of the mission without noticeable improvement or progression. He did not complain of transient visual obscurations, headaches, diplopia, pulsatile tinnitus or visual changes during eye movement. In the months since landing, he has noticed a gradual, but incomplete, improvement in vision. The third case of visual changes while on board the ISS had no changes in visual acuity and no complaints of headaches, transient visual obscurations, diplopia or pulsatile tinnitus during the mission. Upon return to Earth, no eye issues were reported by the astronaut at landing. Fundus examination revealed bilateral, asymmetrical disc edema. There was no evidence of choroidal folds or cotton-wool spots, but a small hemorrhage was observed below the optic dics in the right eye. This astronaut had the most pronounced optic-disc edema of all astronauts reported to date, but had no choroidal folds, globe flattening o
hyperopic shift
At 10 days post landing, an MRI of the brain and eyes was normal, but there appeared to be a mild increase in CSF signal around the right optic nerve. The fourth case of visual changes on orbit was significant for a history of transsphenoidal hypophysectomy for macroadenoma where postoperative imaging showed no residual or recurrent disease. Approximately 2 months into the ISS mission, the astronaut noticed a progressive decrease in near-visual acuity in his right eye and a
scotoma A scotoma is an area of partial alteration in the field of vision consisting of a partially diminished or entirely degenerated visual acuity that is surrounded by a field of normal – or relatively well-preserved – vision. Every normal mamm ...
in his right temporal field of vision. During the same mission, another ISS long-duration astronaut reported the fifth case of decreased near-visual acuity after 3 weeks of spaceflight. In both cases, CO2, cabin pressure and oxygen levels were reported to be within acceptable limits and the astronauts were not exposed to any toxic fumes. The fifth case of visual changes observed on the ISS was noticed only 3 weeks into his mission. This change continued for the remainder of the mission without noticeable improvement or progression. He never complained of headaches, transient visual obscurations, diplopia, pulsatile tinnitus or other visual changes. Upon return to Earth, he noted persistence of the vision changes he observed in space. He never experienced losses in subjective best-corrected acuity, color vision or stereopsis. This case is interesting because the astronaut did not have disc edema or choroidal folds, but was documented to have nerve fiber layer (NFL) thickening, globe flattening, a hyperopic shift and subjective complaints of loss of near vision. The sixth case of visual changes of an ISS astronaut was reported after return to Earth from a 6-month mission. When he noticed that his far vision was clearer through his reading glasses. A fundus examination performed 3 weeks postflight documented a grade 1 nasal optic-disc edema in the right eye only. There was no evidence of disc edema in the left eye or choroidal folds in either eye (Figure 13). MRI of the brain and eyes days postflight revealed bilateral flattening of the posterior globe, right greater than left, and a mildly distended right optic nerve sheath. There was also evidence of optic-disc edema in the right eye. A fundus examination postflight revealed a "new onset" cotton-wool spot in the left eye. This was not observed in the fundus photographs taken 3 weeks postflight. The seventh case of visual changes associated with spaceflight is significant in that it was eventually treated postflight. Approximately 2 months into the ISS mission, the astronaut reported a progressive decrease in his near and far acuity in both eyes. The ISS cabin pressure, CO2 and O2 levels were reported to be within normal operating limits and the astronaut was not exposed to any toxic substances. He never experienced losses in subjective best-corrected acuity, color vision or stereopsis. A fundus examination revealed a grade 1 bilateral optic-disc edema and choroidal folds (Figure 15).


Case definition and clinical practice guidelines

According to guidelines set forth by the Space Medicine Division, all long-duration astronauts with postflight vision changes should be considered a suspected case of VIIP syndrome. Each case could then be further differentiated by definitive imaging studies establishing the postflight presence of optic-disc edema, increased ONSD and altered OCT findings. The results from these imaging studies are then divided into five classes that determine what follow-up testing and monitoring is required.


Classes

The definition of the classes and Frisén scale used for optic disc edema diagnosis are listed below: Class 0 * < 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 ≥ 0.50 diopter cycloplegic refractive change and/or cotton-wool spot * No evidence of optic-disc edema, nerve sheath distention, choroidal folds, globe flattening or scotoma compared to baseline * CSF opening pressure ≤ 25 cm H2O (if measured) Class 2
Repeat OCT, cycloplegic refraction, fundus examination and threshold visual field every 4 to 6 weeks × 6 months, repeat MRI in 6 months * ≥ 0.50 diopter cycloplegic refractive changes or cotton-wool spot * Choroidal folds and/or ONS distention and/or globe flattening and/or scotoma * No evidence of optic-disc edema * CSF opening pressure ≤ 25 cm H2O (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 * ≥ 0.50 diopter cycloplegic refractive changes and/or cotton-wool spot * Optic nerve sheath distention, and/or globe flattening and/or choroidal folds and/or scotoma * Optic-disc edema of Grade 0-2 * CSF opening pressure ≤ 25 cm H2O Class 4
Institute treatment protocol as per Clinical Practice Guideline * ≥ 0.50 diopter cycloplegic refractive changes and/or cotton-wool spot * Optic nerve sheath distention, 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 H2O


Stages

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 vessel. Stage 5 – Severe optic-disc edema
Dome-shaped protrusions representing anterior expansion of the ONG. 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.


Risk factors and recommendations

Risk factors and underlying mechanisms based on anatomy, physiology, genetics and epigenetics need to be researched further. The following actions have been recommended to assist in the research of vision impairment and increased intracranial pressure associated with long-duration space flight:


Immediate actions

* Correlate pre-flight and post-flight MRIs with in-flight Ultrasound * Directly measure intracranial pressure through
lumbar puncture Lumbar puncture (LP), also known as a spinal tap, is a medical procedure in which a needle is inserted into the spinal canal, most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. The main reason for a lumbar puncture is to ...
pre-flight and post-flight on all long duration astronauts * Due to the normal variability in this measurement, obtain more than one pre-flight intracranial pressure measurement through lumbar puncture * Enhanced analysis of OCT findings such as RPE angle * Blinded readings of previous and future diagnostic imaging to minimize potential bias * Measurement of in-flight IOP on all astronauts * Improved in-flight fundoscopic imaging capability * Measurement of pre-flight and post-flight compliance (cranial, spinal, vascular)


Near and long-term actions

* Establish case definition based on curren
Medical Requirements Integration Documents (MRID)
and clinical findings * Develop clinical practice guidelines * Establish a reliable and accurate non-invasive in-flight capability to measure and monitor ICP, compliance and cerebral blood flow * Develop more sophisticated in-flight neurocognitive testing * Establish risk stratification and underlying mechanisms based on anatomy and physiology * Characterization of Human Spaceflight Physiology and Anatomy (human and animal tissue studies) * Develop or utilize advance imaging modalities ( Near Infrared Spectroscopy (NIRS), Transcranial Doppler (TCD), Ophthalmodynanometry, Venous Doppler Ultrasound) * Genetic testing and the use of biomarkers in blood and cerebral spinal fluid (CSF)


Benefits to Earth

The development of accurate and reliable non-invasive ICP measurement methods for VIIP has the potential to benefit many patients on earth who need screening and/or diagnostic ICP measurements, including those with hydrocephalus, intracranial hypertension, intracranial hypotension, and patients with cerebrospinal fluid shunts. Current ICP measurement techniques are invasive and require either a lumbar puncture, insertion of a temporary spinal catheter, insertion of a cranial ICP monitor, or insertion of a needle into a shunt reservoir.


See also

*
Effect of spaceflight on the human body Venturing into the environment of space can have negative effects on the human body. Significant adverse effects of long-term weightlessness include muscle atrophy and deterioration of the skeleton ( spaceflight osteopenia). Other significant e ...

Intracranial Pressure and its Effect on Vision in Space and on Earth
*
Papilledema Papilledema or papilloedema is optic disc swelling that is caused by increased intracranial pressure due to any cause. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare. In ...


References


Citations


Sources

* *


Further reading


Brandon R Macias, John HK Liu, Christian Otto, Alan R Hargens (2017). "Intracranial Pressure & its Effect on Vision in Space and on Earth".
* * * * * * * * * * * {{Space medicine Visual disturbances and blindness Space medicine