SURVEY OF OPHTHALMOLOGY VOLUME 58 � NUMBER 2 � MARCH–APRIL 2013

MAJOR REVIEW

The Effect of Microgravity on Ocular Structuresand Visual Function: A ReviewGiovanni Taibbi, MD,1 Ronita L. Cromwell, PhD,2 Kapil G. Kapoor, MD,1

Bernard F. Godley, MD, PhD,1 and Gianmarco Vizzeri, MD1

1Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, Texas; and2Universities Space Research Association, Division of Space Life Sciences, Houston, Texas, USA

� 2013 byAll rights

Abstract. Ocular structural and functional changes, including optic disk edema and reduction ofnear visual acuity, have been recently described in some astronauts returning from long-duration spacetravels. It is hypothesized that ocular changes related to spaceflight may occur, in predisposedindividuals, as a result of cephalad shift of body fluids, possibly leading to elevated intracranial pressure(ICP). Results from head-down bed-rest studies (used to simulate the effects of microgravity) and fromparabolic flight experiments (used to produce transient periods of microgravity) indicate that ocularblood flow and intraocular pressure (IOP) may undergo changes in a low-gravity environment. Recentstudies suggest that changes in translaminar pressure (i.e., IOP minus ICP) may be implicated in thepathophysiology of optic disk neuropathies. Because postural changes exert an effect on both IOP andICP, the head-down bed-rest analog may also be used as a platform to characterize the relationshipbetween IOP and ICP, and their reciprocal influence in the pathophysiology of conditions such as opticdisk edema or glaucoma. (Surv Ophthalmol 58:155--163, 2013. � 2013 Elsevier Inc. All rightsreserved.)

Key words. astronauts � bed rest � intracranial pressure � intraocular pressure �microgravity � papilledema � spaceflight � translaminar pressure

I. Introduction

The effects of space travel on the human body havebeen studied since the first human spaceflight in1961. For example, it is known that reduced gravityproduces multi-systemic effects on crewmembers,such as bone demineralization,34,71 muscle atro-phy,21,76 cardiovascular deconditioning,53,58,75 ves-tibular and sensory imbalance6,37,66 (includingvestibulo-ocular conflicts in space adaptation syn-drome36), altered metabolic and nutritional sta-tus,72,84,85 and dysregulation of the immunesystem.10,11 Generally, the severity of the alterationsis related to the duration of the spaceflight, but the

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individual’s ability to adapt to the microgravityenvironment and the efficacy of the countermea-sures also play a role.55

Exposure to microgravity may also cause ocularstructural and functional changes, posing a risk tothe safety and success of a human space explorationprogram. Planning for long-duration (O30 days)human explorations to the asteroids and Marsrequires a better understanding of the effects ofmicrogravity on the visual system and implementa-tion of adequate countermeasures. For this purpose,research on Earth largely relies on the head-downtilt bed-rest analog.54

0039-6257/$ - see front matterdoi:10.1016/j.survophthal.2012.04.002

156 Surv Ophthalmol 58 (2) March--April 2013 TAIBBI ET AL

We review the effects of microgravity on ocularstructures and visual function and present ophthal-mological findings in astronauts and results fromhead-down bed-rest studies. In addition, the poten-tial clinical implications deriving from the spaceexperience and ground-based studies, with regard tothe pathophysiology of optic disk neuropathies, arediscussed.

II. Ocular Changes Related to Spaceflight

The effects of orbital spaceflights on ocularstructures and visual function are largely unknown.While in orbit, the astronauts seem to have anincreased risk of cataract formation from exposure tospace radiation and ultraviolet rays.9,12,17,30,39,60,82

Astronauts who participated in the Space Shuttle andthe International Space Station (ISS) programsexperienced visual changes.43,A Specifically, withregard to the Space Shuttle program (generally 10-to 14-day missions), some astronauts complained ofreduction of near visual acuity that resolved uponreturning to Earth. Ophthalmological examinationsperformed on astronauts returning from ISS mis-sions (average 6-month duration) showed signs ofvarious degrees of optic disk edema in several cases.Severe cases presented with signs of globe flatteningwith hyperopic shifts, choroidal folds, and cottonwool spots, resulting in permanent visual impairmentin some cases. Interestingly, these changes appearedto be associated with elevated intracranial pressure(ICP) measured with lumbar puncture (LP).43

The exact risk factors that subject individuals tovisual disturbances and vision loss are unknown andfurther research is needed. Eventually, knowledge ofthe risk factors may lead to the implementation ofmore rigorous criteria for astronaut selection andmission assignment to reduce the rate/severity ofvisual changes and, at the same time, to increase thechances of the success of long-duration spacemissions. ‘‘Space anticipation glasses,’’ plus lensesroutinely offered pre-flight to NASA astronauts tocorrect for potential hyperopic shifts, are the onlycurrently available countermeasure to ensure goodvisual performance throughout the mission.43

Likewise, the mechanisms responsible for theocular changes described in the astronauts are notwell understood. One hypothesis is that thesefindings may occur, in predisposed individuals, asa result of spaceflight-induced cephalad shift ofbody fluids, possibly leading to elevated ICP. Aspointed out by Mader and associates,43 strongsimilarities exist between some of the structuralchanges described earlier (e.g., optic disk edema,globe flattening, choroidal folds) and those no-ticed in patients with idiopathic intracranial

hypertension (IIH). On the other hand, typicalsymptoms of IIH, such as headaches, transientvisual obscurations, or pulse synchronous tinni-tus,79 were not reported by the crewmembers. Abetter understanding of the effect of microgravityon ocular structures and visual function may haveimportant implications in the management of IIHbecause both conditions may share commonpathophysiological mechanisms.

Alternative hypotheses to explain the origin of theastronauts findings are a local disruption of cere-brospinal fluid (CSF) dynamics at the level of theorbital optic nerve sheath leading to optic nervecompartment syndrome with subsequent disk alter-ations, not necessarily accompanied by increasedICP, or ocular hypotony. There are several reports ofintraocular pressure (IOP) reductions from baselineon astronauts upon returning to Earth and inhealthy patients during long-duration bed-reststudies (see Section IV.A Intraocular Pressure andCardiovascular Changes). Although the comparisonwith terrestrial conditions, such as IIH, may helpunderstanding the nature of microgravity-inducedvisual changes, research is necessary to confirm theproposed pathophysiological mechanisms.

III. Head-down Tilt Bed-rest Analog

NASA’s plan for long duration human spaceexplorations requires implementation of adequatecountermeasures to manage physiological changesinduced by spaceflight, but, given the limitedresources for in-flight development and validationof countermeasures, research must be mainlyconducted on Earth. Head-down tilt bed rest haslong been utilized to simulate the effects ofmicrogravity on the human body and to studypotential countermeasures.54 Specifically, long-duration, 6� head-down bed rest produces many ofthe physiological modifications induced by space-flight, such as cephalad shift of body fluids, muscleand bone atrophy, decreased metabolic require-ments, and reduced stimulation of the sensorysystem.54 Space is a unique environment character-ized by the simultaneous absence of transverse (Gx)and longitudinal (Gz, head to toe) gravitationalstress. Head-down bed rest does not eliminate Gxinfluence, although the adoption of a terrestrialanalog has some potential advantages: reducingresearch-related costs; conducting studies witha larger sample size compared to the astronautcrews; allowing for the possibility of performinglong-term integrated, multidisciplinary investiga-tions; and using instrumentation and facilities thatcould not be easily allocated onboard thespacecrafts.

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IV. Posture-induced Ocular Changes

Posture-induced ocular changes are described fora variety of time lengths and angles of tilt. Bed-reststudies were primarily used to characterize therelationship between body position and IOP.59 Lessis known about the effects on ocular perfusionpressure (OPP), choroidal blood flow (ChBF) andcaliber of retinal blood vessels, partly due to difficul-ties in obtaining reliable and accurate measurements.

A. INTRAOCULAR PRESSURE AND

CARDIOVASCULAR CHANGES

Acute changes in IOP are well documented forshort duration studies ranging from 2 minutes to48 hours.7,18,31,41,46,83 In these studies, IOP showedan immediate increase when the body was placed ina recumbent position. This increase in IOP rangedfrom 2 to 5 mm Hg for body angles of 0�,31 --8�,41

--10�,18,46 --15�,7,83 and --50�.7 IOP demonstrateddiurnal variations in a --10� position over the courseof 48 hours showing a drop in IOP at night.46

Increased IOP was accompanied by a drop in heartrate31,41 and changes in blood pressure.31,41,83

These studies documented decreased diastolicblood pressure; systolic blood pressure varied,however, depending upon the time spent in therecumbent position. At the end of 2 minutes, nochange was seen in systolic blood pressure.41 Incontrast, at the end of 21 and 30 minutes at --15�

and 0�, respectively, systolic blood pressure de-creased.31,83 This change was gradual, reachingsignificance at 6 minutes.83

Bed-rest data showing blood pressure reductionassociated with IOP elevation may be relevant topatients with cardiovascular risk factors undergoingprolonged surgical procedures in a tilted position(e.g., spine surgery). In such situations, the opticnerve may suffer from insufficient blood supply andelevated IOP. Ischemic optic neuropathy, for exam-ple, is a cause of permanent perioperative vision lossafter spine surgery.52 The American Society ofAnesthesiologists Task Force on Perioperative VisionLoss emphasizes the importance of continuousblood pressure monitoring in high-risk patientsundergoing spine surgery.1

Cephalad shifts of body fluids in response to tiltmay be a factor responsible for increased IOP (seesection V. Intraocular Pressure and Microgravity).These shiftsmay occur in response to tilt, as suggestedafter measuring the thoracic fluid index (TFI),35

a cardiovascular parameter that is inversely related tothe relativefluid content of the thorax and it is used toindirectly determine cephalad fluid shifts. TFI wasmeasured in conjunction with IOP over 48 hours ofbed rest at --10�.18 By 12 hours, as the result of

a decrease in thoracic fluids, TFI had increased, thussuggesting the occurrence of cephalad body fluidshifts. This change persisted after 48 hours of bed restand paralleled the increase in IOP.18

Longer durations of bed rest have produceddiffering results. Chiquet and colleagues firstexamined the acute response in IOP over a10-minute interval as patients moved from thesitting to supine position.8 These changes weresimilar to those reported by other groups who foundan increase in IOP over this time frame.41,83 Whenstudied over 7 days of --6� bed rest, IOP progressivelydecreased when measured on days 1, 3, 5 and 7.8

This decrease was significant by days 5 and 7. IOPreturned to baseline levels within 2 days post bedrest. Plasma volume measures paralleled IOP,showing a progressive decrease that was significantby day 7 of bed rest. Correlation between IOP andplasma volume changes during bed rest wassignificant (r 5 0.61; p 5 0.02). Similar tospaceflight, plasma volume reduction in head-down bed rest results from cephalad shift of bodyfluids leading to stimulation of baroreceptors, withsubsequent diuresis.57

Mekjavic and colleagues measured visual acuity,stereoscopic vision, contrast sensitivity, IOP, andvisual field over 35 days of 0� bed rest.47 Patients wereevaluated before and after bed rest. No differencesfrom baseline for any of these measures were found.The lack of difference may be partially explained bythe timing of post--bed rest evaluations. Data werecollected on the second or third day after bed rest.Based on the findings for IOP described above,8

changes in dependent measures may have alreadyresolved by 2 days following bed rest.

A study examining 70 days of 0� bed rest founddecreased IOP, constricted visual field, increasedblind spot, reduced visual acuity, and a more distantnear point of clear vision.16 By 20 days following bedrest, changes in the blind spot and visual acuity werenot fully resolved. The descriptive informationpresented in this study was not rigorously analyzedand should be interpreted with caution.

Oneof themajor limitationsofbed rest studies is thelack of standardization (e.g., variability in the durationof bed rest and angle of tilt). Standardized conditionsand measurements are necessary to ensure directcomparison of the results from independent groups,as well as with data collected on astronauts duringactual spaceflights or upon return on Earth.

B. OCULAR PERFUSION PRESSURE AND

CHOROIDAL BLOOD FLOW

A limited number of studies have been specificallydesigned to evaluate the effect of body position on

158 Surv Ophthalmol 58 (2) March--April 2013 TAIBBI ET AL

OPP and ChBF. Calculated values of OPP increasedin response to 30, 2, and 21 minutes of body tilt at0�,31 --8�,41 and --15�,83 respectively. In one study,measurements of subfoveal ChBF demonstrated an11% increase after 2 minutes at --8� tilt.41 This ChBFincrease was associated with an þ8% increase inchoroidal blood velocity, although subfoveal choroi-dal blood volume appeared not to be substantiallydifferent from the seated position. As opposed toChBF in the subfoveal choriocapillaris, choroidalblood volume cannot be reliably quantified withavailable technology. In another study, ChBF dem-onstrated a 12% decrease in response to 30 minutesin a supine position.31 These authors then recalcu-lated OPP as they believed the ophthalmic arterialblood pressure used to calculate OPP was over-estimated. Recalculation of OPP plotted againstChBF demonstrated that both variables decreaseduniformly. The contrasting findings of these studieswere explained by the differences in the time frameof each study;31the authors of these studies came tothe same conclusion, however, that similarity inchanges of OPP and ChBF suggest a passive re-sponse to changes in body posture.

Exposure to microgravity may increase ChBF. Inan experiment conducted during parabolic flight,which produces 20--30 seconds of microgravity,Ansari et al measured ChBF on five healthy in-dividuals using a head-mounted laser-Doppler flow-meter.2,B During transient microgravity, ChBFincreased in all patients.

C. RETINAL BLOOD VESSELS

In two different studies the caliber of retinal veinsand arteries immediately decreased in response toa --10� position.18,46 This immediate response wasnot progressive as values remained the same after48 hours of --10� bed rest. These changes in retinalveins and arteries may be an autoregulatory re-sponse that acts to maintain retinal perfusion.46

Changes in caliber of retinal veins and arteriescorrelated with decreased velocity of blood in themiddle cerebral artery. The authors hypothesizedthat increased cerebral venous and capillary pres-sures could elicit a dilation response in largercerebral vessels like the middle cerebral artery.18

These posture-induced changes in the retinalvasculature confirmed previous observations byFriberg and associates, who found a decrease inthe caliber of retinal arterioles following bodyinversion.20

Parabolic flight was used to investigate the effectof microgravity on retinal blood vessels. Mader andcolleagues analyzed a series of fundus photographscollected on 11 healthy individuals during transient

periods of microgravity onboard the KC-135 ZeroGravity Aircraft.44 The authors detected a 4% re-duction in the caliber of retinal arteries. The changewas not statistically significant, possibly due to thesmall sample size; this finding may suggest an acuteresponse to microgravity similar to that describedfor bed rest, however.

V. Intraocular Pressure and Microgravity

Scattered reports suggest that IOP may rise inmicrogravity.45 For example, measurements onastronauts revealed IOP elevation during the firstdays of flight with subsequent decrease andnormalization.A

During parabolic flight, Draeger et al docu-mented a mean 5 mm Hg increase in IOP usinga hand-held applanation tonometer,14,15 and Maderet al reported a mean 7 mm Hg increase in IOP(þ58%) using a TonoPen.44

This IOP elevation is likely due to microgravity-induced cephalad fluid shift. The rise in IOPoccurring a few seconds after exposure to micro-gravity may result from choroidal engorgement andexpansion.33,42,44,46,81 Microgravity would producea sudden increase in the pressure of the vortexveins, thus inhibiting the venous drainage andcausing a slight increase in choroidal volume,a process favored by the lack of choroidal vascularautoregulation. Because fluids are incompressible,choroidal expansion against the rigid scleral tissuewould lead to a sudden IOP elevation.43 Also, itshould be noted that increased episcleral venouspressure induced by cephalad fluid shift, determin-ing an increase in aqueous humor outflow re-sistance, may significantly contribute to the rise inIOP after more prolonged periods of microgravity.19

It is possible that neuro-vegetative mechanisms, orother compensatory mechanisms such as decreasedaqueous humor production,46 may activate afterlong duration spaceflights, as anecdotal reportssuggest that IOP may significantly decrease belowpre-flight values upon returning to Earth.A

Changes in IOP may be harmful in predisposedindividuals. The risk of developing glaucoma in-creases substantially with the level of IOP eleva-tion.80 On the other hand, a decrease in IOPassociated with an increase in ICP may result ina decrease in translaminar pressure (i.e., thedifference between IOP and ICP, see section VII.‘‘Translaminar Pressure’’ and Optic Nerve HeadAbnormalities), which may ultimately lead to thedevelopment of optic disk edema.

Assessment of corneal biomechanics is an impor-tant factor for accurate interpretation of IOP.40

Corneal biomechanical properties, such as central

MICROGRAVITY AND VISUAL FUNCTION 159

corneal thickness or corneal hysteresis, have notbeen systematically evaluated in a microgravityenvironment. Modifications of these propertiesmay considerably affect IOP measurements. Inaddition, corneal biomechanics may reflect theproperties of the lamina cribrosa and the peripapil-lary sclera and, therefore, the susceptibility of anindividual to develop optic nerve changes in theabsence of gravity.

VI. Intracranial Pressure andMicrogravity

A. THE EFFECT OF MICROGRAVITY ON

INTRACRANIAL FLUID HOMEOSTASIS

Cephalad fluid shift may be implicated in theonset of intracranial hypertension with secondaryophthalmologic sequelae after long duration spacetravel. Based on the few case reports available on theastronauts, ICP was elevated in most cases in whichoptic disk edema was also clinically evident.43,A,C

CSF homeostasis relies on a complex interplay ofmultiple factors, including biochemical and neuro-vegetative influences, and it is important to considereach of these in deciphering the etiology of elevatedICP. Normal CSF is a clear, bright fluid thatcirculates through the subarachnoid space andprovides neuroprotective, metabolic, immunologic,and scavenging functions for the central nervoussystem.32 The choroid plexuses in the ventricles arethe site of CSF production, with ultimate egress intothe venous system via the arachnoid granulations orlymphatic capillaries.

ICP dynamics were examined using ultrasoundtechniques before and after 30 days of 6� head-downbed rest.74 Measures were taken with patients in thesupine position. Ultrasound measured oscillationsof the temporal bone to capture small displace-ments that occur during systole and diastole.Changes in compliance of these movements arerelated to ICP changes. Displacement amplitudesdecreased by 10 mm, indicating altered intracranialcompliance. Post-bed-rest amplitudes were similar tothose of upright posture, indicating a possibledecrease in ICP by the end of bed rest. Furtherstudies are needed to systematically evaluate theeffects of long duration orbital space travel on thecomplex control of CSF homeostasis, along with thepotential etiologies of elevated ICP.

B. INTRACRANIAL PRESSURE MEASUREMENT IN

MICROGRAVITY

LP is currently the accepted standard for assessingICP in clinical practice, but the procedure carriessome risks of hemorrhage and infection and is

contraindicated in some individuals. Clearly, LP isnot feasible in microgravity.

Indirect, noninvasive measures of ICP have beenproposed. These include the use of differenttechnologies, such as computed tomography, mag-netic resonance imaging, transcranial Dopplersonography, audiometric techniques, near infraredspectroscopy, visual-evoked potentials, ophthalmo-dynamometry, optical coherence tomography(OCT), confocal scanning laser ophthalmoscopy(CSLO), or ultrasounds to non-invasively estimateICP,67 but studies aimed at comparing measurementreliability between different techniques are lacking.

Audiometric techniques to evaluate tympanicmembrane (TM) displacement are a promisingmethod to indirectly assess ICP. In fact, changes inICP are reflected in perilymphatic fluid through thecochlear aqueduct, thus altering the resting positionof the ossicular chain and TM. A portable, non-invasive prototype has been designed and tested toestimate ICP.22,49,69 Murthy et al found significantTM displacements as patients moved from thesitting to 0�, --6�, and --15� head-down tilt positions.They estimated a rise in ICP from 2 mm Hg in thesitting position to 17 mm Hg in the --6� head-downposture.51 Although there is a moderate correlationbetween TM displacement measurements and ICP,62

it is unclear whether audiometric techniques canserve as a surrogate for ICP.70

A non-invasive method to evaluate ICP wouldallow for close monitoring of astronauts’ ICP whilein space. If indicated, adequate medical treatmentaimed at lowering ICP could be promptly instituted.Acetazolamide, for example, is a carbonic anhydraseinhibitor that reduces CSF production and appearsto be effective in IIH.38 Acetazolamide has beensuggested as a treatment for symptomatic crewmem-bers with optic disk edema.A Because the underlyingmechanism is unknown, on-board medical manage-ment of asymptomatic cases was discouraged. Inaddition, it is important to consider that acetazol-amide induces a relative dehydration that mayfurther exacerbate the risk of renal calculi inspace.56 Also, data on efficacy and safety of on-board medical treatments for any ocular conditionare not available at present.

VII. ‘‘Translaminar Pressure’’ and OpticNerve Head Abnormalities

Recent reports have documented a correlationbetween changes in the optic disk (measured usingimaging technology such as CSLO24,50,64,68,77 andOCT25,61) and elevated ICP. Also, similarities be-tween the CSF and aqueous humor dynamics arewell known. Specifically, it has been shown that

160 Surv Ophthalmol 58 (2) March--April 2013 TAIBBI ET AL

a similar dynamic system of transcellular pores isa common outflow pathway for the CSF andaqueous humor.78 The term ‘‘glaucoma of thebrain,’’ used in the past to describe conditions suchas pseudotumor cerebri, served to highlight theanalogy between the homeostatic and drainagemechanisms of the eye and the brain rather thantheir reciprocal correlation (i.e., elevated pressureimplied increased outflow resistance across thetrabecular meshwork and the arachnoid granula-tions, respectively).13

ICP and IOP may both play a critical role in thedevelopment of optic nerve damage.4,26,27,65,73 Infact, ‘‘translaminar pressure,’’ that is, the pressuredifference between IOP and ICP, may producechanges at the level of the optic nerve head inpredisposed eyes. High myopic eyes in which thelamina cribrosa and/or the peripapillary sclera maybe abnormally thin and/or eyes in which thebiomechanical properties of the lamina cribrosaand peripapillary sclera are abnormal are likely to bemore susceptible to damage caused by changes intranslaminar pressure.3,28,29,48 In addition, quanti-tative and/or qualitative differences in the arach-noid trabeculations at the level of the optic diskcanal may be of importance. These fibrous bandsform a trabecular meshwork that reduces the CSFflow into the orbital optic nerve sheath.23 Paucity ofarachnoid trabeculations may facilitate the commu-nication between the intracranial and the intra-orbital portions of the optic nerve sheath, thusresulting in increased optic disk susceptibility todamage caused by ICP changes. This has potentialclinical implications. For example, the presence ofinterocular differences between the arachnoidtrabeculations, leading to unequal ICP forcingagainst the retrolaminar optic nerves of an in-dividual, is the most plausible explanation forasymmetric disk edema in IIH.38

ICP may counteract the effects of IOP on theoptic nerve head and vice versa. For example,a decrease in IOP associated with an increase inICP may result in a decrease in translaminarpressure, ultimately leading to the development ofoptic disk edema.3

On the other hand, an increase in translaminarpressure may result from an increase in IOP,a decrease in ICP, or a combination of both. Tworetrospective studies have found an increasedtranslaminar pressure in glaucoma patients.4,5 Thisfinding was confirmed in a prospective study byRen et al.65 The same investigators have recentlyfound that ICP was significantly higher in 17 ocularhypertensive patients compared with the 71 con-trols and suggested that ICP may compensate forthe elevated IOP.63 Further study should clarify

whether changes in translaminar pressure result-ing from changes in IOP and/or ICP may havea role in the pathophysiology of optic diskneuropathies.

VIII. Conclusion

The effects of microgravity on ocular structuresand visual function are largely unknown. Currentknowledge mainly derives from scattered reports,and undoubtedly more research is needed inpreparation for long-duration human space explo-rations. Head-down tilt bed-rest analog has beenused to simulate the effects of microgravity on thevisual system; standardized conditions and measure-ments are required to ensure direct comparison ofthe results from independent groups, however, aswell as with data collected on astronauts.

Recent studies suggest that changes in trans-laminar pressure may play a role in the pathogenesisof optic disk diseases, but further investigation iswarranted to confirm this hypothesis. Becausepostural changes exert an effect on both IOP andICP, head-down tilt bed rest analog may also be usedas a platform to characterize the relationshipbetween IOP and ICP and their reciprocal influencein the pathophysiology of conditions such as opticdisk edema or glaucoma.

IX. Method of Literature Search

An online literature search was conductedthrough Pubmed database and NASA TechnicalReport Server. The following key words, alone or incombination, were used: astronauts, bed rest, cata-ract, choroidal blood flow, confocal scanning laserophthalmoscopy, glaucoma, idiopathic intracranial hy-pertension, intracranial pressure, intraocular pressure,measurement, microgravity, OCT, ocular changes, ocularperfusion pressure, optic nerve sheath, papilledema,parabolic flight, pseudotumor cerebri, space radiation,space adaptation syndrome, spaceflight, translaminarpressure, tympanic membrane displacement, and vision.Reference lists were inspected for all studiesincluded in this review. Meeting abstracts wereincluded only if they provided additional meaning-ful information.

Disclosure

The authors report no financial or proprietaryinterests in any product mentioned or conceptdiscussed in this article. Publication of this articlewas supported by Research to Prevent Blindness(New York, NY) Challenge Grant.

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References

1. American Society of Anesthesiologists Task Force onPerioperative Visual Loss. Practice advisory for perioperativevisual loss associated with spine surgery: an updated reportby the American Society of Anesthesiologists Task Force onPerioperative Visual Loss. Anesthesiology. 2012;116:274--85

2. Ansari RR, Kwang IS, Moret F, et al. Measurement ofchoroidal blood flow in zero gravity. Proc SPIE. 2003;4951:177--84

3. Berdahl JP, Allingham RR. Intracranial pressure andglaucoma. Curr Opin Ophthalmol. 2010;21:106--11

4. Berdahl JP, Fautsch MP, Stinnett SS, et al. Intracranialpressure in primary open angle glaucoma, normal tensionglaucoma, and ocular hypertension: a case-control study.Invest Ophthalmol Vis Sci. 2008;49:5412--8

5. Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluidpressure is decreased in primary open-angle glaucoma.Ophthalmology. 2008;115:763--8

6. Bock O, Weigelt C, Bloomberg JJ. Cognitive demand ofhuman sensorimotor performance during an extendedspace mission: a dual-task study. Aviat Space Environ Med.2010;81:819--24

7. Carlson KH, McLaren JW, Topper JE, et al. Effect of bodyposition on intraocular pressure and aqueous flow. InvestOphthalmol Vis Sci. 1987;28:1346--52

8. Chiquet C, Custaud MA, Le Traon AP, et al. Changes inintraocular pressure during prolonged (7-day) head-downtilt bedrest. J Glaucoma. 2003;12:204--8

9. Chylack LT Jr, Peterson LE, Feiveson AH, et al. NASA studyof cataract in astronauts (NASCA). Report 1: Cross-sectionalstudy of the relationship of exposure to space radiation andrisk of lens opacity. Radiat Res. 2009;172:10--20

10. Crucian BE, Stowe RP, Mehta SK, et al. Immune status,latent viral reactivation, and stress during long-durationhead-down bed rest. Aviat Space Environ Med. 2009;80(Suppl 5):A37--44

11. Crucian BE, Stowe RP, Pierson DL, et al. Immune systemdysregulation following short- vs long-duration spaceflight.Aviat Space Environ Med. 2008;79:835--43

12. Cucinotta FA, Manuel FK, Jones J, et al. Space radiation andcataracts in astronauts. Radiat Res. 2001;156(5 Pt 1):460--6,[erratum in Radiat Res 2001;156:811].

13. Delperier A. Identite entre pressions intraoculaire et intra-cranienne. Agressologie. 1983;24:445--52

14. Draeger J, Wirt H, Schwartz R. TOMEX, Messung desAugeninnendrucks unter micro-G--Bedingungen. Naturwis-senschaften. 1986;73:450--2

15. Draeger J, Wirt H, Schwartz R. Tonometry under micrograv-ity conditions, in Sahm PR, Jansen R, Keller MH (eds).Norderney Symposium on Scientific Results of the GermanSpacelab Mission D1. Norderney, Germany, 1986, pp 503--9

16. Drozdova NT, Nesterenko OP. State of the visual analyzerduring hypodynamia, in Genin AM, Sorokin PA (eds),Problems of Space Biology: Prolonged Limitation of Motilityand its Influence. vol. 13. Moscow, Russian Federation,Nauka Press; 1970, pp 189--91

17. Frey MA. Radiation health: mechanisms of radiation-induced cataracts in astronauts. Aviat Space Environ Med.2009;80:575--6

18. Frey MA, Mader TH, Bagian JP, et al. Cerebral blood velocityand other cardiovascular responses to 2 days of head-downtilt. J Appl Physiol. 1993;74:319--25

19. Friberg TR, Sanborn G, Weinreb RN. Intraocular andepiscleral venous pressure increase during inverted posture.Am J Ophthalmol. 1987;103:523--6

20. Friberg TR, Weinreb RN. Ocular manifestations of gravityinversion. JAMA. 1985;253:1755--7

21. Gopalakrishnan R, Genc KO, Rice AJ, et al. Muscle volume,strength, endurance, and exercise loads during 6-monthmissions in space. Aviat Space Environ Med. 2010;81:91--102

22. Hargens AR. Recent bed rest results and countermeasuredevelopment at NASA. Acta Physiol Scand. 1994;616(Suppl):103--14

23. Hayreh SS. The sheath of the optic nerve. Ophthalmologica.1984;189:54--63

24. Heckmann JG, Faschingbauer F, Lang C, et al. Laser scanningtomographymeasurement of the extent of papilledema in thefollow-up examination of patients with idiopathic intracranialhypertension. J Neurosurg. 2007;107:543--7

25. Heidary G, Rizzo JF 3rd. Use of optical coherencetomography to evaluate papilledema and pseudopapillede-ma. Semin Ophthalmol. 2010;25:198--205

26. Jonas JB,WangN. Association between arterial blood pressure,cerebrospinal fluid pressure and intraocular pressure in thepathophysiology of optic nerve head diseases. Clin Experi-ment Ophthalmol. [E-Pub ahead of Publication. http://dx.doi.org/10.1111/j.1442-9071.2011.02625.x.]

27. Jonas JB. Role of cerebrospinal fluid pressure in thepathogenesis of glaucoma. ActaOphthalmol. 2011;89:505--14

28. Jonas JB, Berenshtein E, Holbach L. Lamina cribrosathickness and spatial relationships between intraocularspace and cerebrospinal fluid space in highly myopic eyes.Invest Ophthalmol Vis Sci. 2004;45:2660--5

29. Jonas JB, Berenshtein E, Holbach L. Anatomic relationshipbetween lamina cribrosa, intraocular space, and cerebrospi-nal fluid space. Invest Ophthalmol Vis Sci. 2003;44:5189--95

30. Jones JA, McCarten M, Manuel K, et al. Cataract formationmechanisms and risk in aviation and space crews. AviatSpace Environ Med. 2007;78(Suppl 4):A56--66

31. Kaeser P, Orgul S, Zawinka C, et al. Influence of change inbody position on choroidal blood flow in normal subjects.Br J Ophthalmol. 2005;89:1302--5

32. Kapoor KG, Katz SE, Grzybowski DM, et al. Cerebrospinalfluid outflow: an evolving perspective. Brain Res Bull. 2008;77:327--34

33. Kergoat H, Lovasik JV. Seven-degree head-down tilt reduceschoroidal pulsatile ocular blood flow. Aviat Space EnvironMed. 2005;76:930--4

34. Keyak JH, Koyama AK, LeBlanc A, et al. Reduction inproximal femoral strength due to long-duration spaceflight.Bone. 2009;44:449--53

35. Kubicek WG, Kottke J, Ramos MU, et al. The Minnesotaimpedance cardiograph: theory and applications. BiomedEng. 1974;9:410--6

36. Lackner JR, Dizio P. Space motion sickness. Exp Brain Res.2006;175:377--99

37. Layne CS, Mulavara AP, McDonald PV, et al. Effect of long-duration spaceflight on postural control during self-generated perturbations. J Appl Physiol. 2001;90:997--1006

38. Lee AG, Wall M. Papilledema: are we any nearer toa consensus on pathogenesis and treatment? Curr NeurolNeurosci Rep. 2012;12:334--9

39. Lett JT, Lee AC, Cox AB. Risks of radiation cataracts frominterplanetary space missions. Acta Astronaut. 1994;32:739--48

40. Liu J, Roberts CJ. Influence of corneal biomechanicalproperties on intraocular pressure measurement. J CataractRefract Surg. 2005;31:146--55

41. Longo A, Geiser MH, Riva CE. Posture changes andsubfoveal choroidal blood flow. Invest Ophthalmol Vis Sci.2004;45:546--51

42. Lovasik JV, Kergoat H. Gravity-induced homeostatic re-actions in the macular and choroidal vasculature of thehuman eye. Aviat Space Environ Med. 1994;65:1010--4

43. Mader TH, Gibson CR, Pass AF, et al. Optic disc edema,globe flattening, choroidal folds, and hyperopic shiftsobserved in astronauts after long-duration space flight.Ophthalmology. 2011;118:2058--69

44. Mader TH, Gibson CR, Caputo M, et al. Intraocular pressureand retinal vascular changes during transient exposure tomicrogravity. Am J Ophthalmol. 1993;115:347--50

45. Mader TH. Intraocular pressure in microgravity. J ClinPharmacol. 1991;31:947--50

46. Mader TH, Taylor GR, Hunter N, et al. Intraocular pressure,retinal vascular and visual acuity changes during 48 hours of10 degrees head-down tilt. Aviat Space Eviron Med. 1990;61:810--3

162 Surv Ophthalmol 58 (2) March--April 2013 TAIBBI ET AL

47. Mekjavic PJ, Eiken O, Mekjavic IB. Visual function afterprolonged bed rest. J Gravit Physiol. 2002;9:P31--2

48. Morgan WH, Yu DY, Balaratnasingam C. The role ofcerebrospinal fluid pressure in glaucoma pathophysiol-ogy: the dark side of the optic disc. J Glaucoma. 2008;17:408--13

49. Moss SM, Marchbanks RJ, Burge DM. Non-invasive assess-ment of ventricular shunt function using tympanic mem-brane displacement measurement technique. Z Kinderchir.1990;45(Suppl 1):26--8

50. Mulholland DA, Craig JJ, Rankin SJ. Use of scanninglaser ophthalmoscopy to monitor papilloedema in idio-pathic intracranial hypertension. Br J Ophthalmol. 1998;82:1301--5

51. Murthy G, Marchbanks RJ, Watenpaugh DE, et al. Increasedintracranial pressure in humans during simulated micro-gravity. Physiologist. 1992;35(Suppl 1):S184--5

52. Newman NJ. Perioperative visual loss after nonocularsurgeries. Am J Ophthalmol. 2008;145:604--10

53. Nicogossian AE, Parker JF Jr. Space Physiology and Medicine(NASA SP-447). Washington, DC, U.S. Government PrintingOffice; 1982. 165--166.

54. Pavy-Le Traon A, Heer M, Narici MV, et al. From space toEarth: advances in human physiology from 20 years ofbed rest studies (1986--2006). Eur J Appl Physiol. 2007;101:143--94

55. Payne MW, Williams DR, Trudel G. Space flight rehabilita-tion. Am J Phys Med Rehabil. 2007;86:583--91

56. Pietrzyk RA, Jones JA, Sams CF, et al. Renal stone formationamong astronauts. Aviat Space Environ Med. 2007;78(Suppl4):A9--13

57. Platts SH, Martin DS, Stenger MB, et al. Cardiovascularadaptations to long-duration head-down bed rest. AviatSpace Environ Med. 2009;80(Suppl 5):A29--36

58. Platts SH,ZieglerMG,WatersWW, et al.Hemodynamic effectsof midodrine after spaceflight in astronauts without ortho-static hypotension. Aviat Space Eviron Med. 2006;77:429--33

59. Prata TS, De Moraes CG, Kanadani FN, et al. Posture-induced intraocular pressure changes: considerationsregarding body position in glaucoma patients. Surv Oph-thalmol. 2010;55:445--53

60. Rastegar N, Eckart P, Mertz M. Radiation-induced cataract inastronauts and cosmonauts. Graefes Arch Clin Exp Oph-thalmol. 2002;240:543--7

61. Rebolleda G, Munoz-Negrete FJ. Follow-up of mild papil-ledema in idiopathic intracranial hypertension with opticalcoherence tomography. Invest Ophthalmol Vis Sci. 2009;50:5197--200

62. Reid A, Marchbanks RJ, Burge DM, et al. The relationshipbetween intracranial pressure and tympanic membranedisplacement. Br J Audiol. 1990;24:123--9

63. Ren R, Zhang X, Wang N, et al. Cerebrospinal fluid pressurein ocular hypertension. Acta Ophthalmol. 2011;89:e142--8

64. Ren R, Wang N, Zhang X, et al. Trans-lamina cribrosapressure difference correlated with neuroretinal rim area inglaucoma. Graefes Arch Clin Exp Ophthalmol. 2011;249:1057--63

65. Ren R, Jonas JB, Tian G, et al. Cerebrospinal fluid pressurein glaucoma: a prospective study. Ophthalmology. 2010;117:259--66

66. Reschke MF, Bloomberg JJ, Paloski WH, et al. Posturalreflexes, balance control, and functional mobility with long-duration head-down bed rest. Aviat Space Environ Med.2009;80(Suppl 5):A45--54

67. Rosenberg JB, Shiloh AL, Savel RH, et al. Non-invasivemethods of estimating intracranial pressure. Neurocrit Care.2011;15:599--608

68. Salgarello T, Falsini B, Tedesco S, et al. Correlation of opticnerve head tomography with visual field sensitivity inpapilledema. Invest Ophthalmol Vis Sci. 2001;42:1487--94

69. Samuel M, Burge DM, Marchbanks RJ. Tympanic membranedisplacement testing in regular assessment of intracranialpressure in eight children with shunted hydrocephalus.J Neurosurg. 1998;88:983--95

70. Shimbles S, Dodd C, Banister K, et al. Clinical comparison oftympanic membrane displacement with invasive ICP mea-surements. Acta Neurochir. 2005;95(Suppl):197--9

71. Sibonga JD, Evans HJ, Sung HG, et al. Recovery ofspaceflight-induced bone loss: bone mineral density afterlong-duration missions as fitted with an exponentialfunction. Bone. 2007;41:973--8

72. Smith SM, Zwart SR. Nutritional biochemistry of spaceflight.Adv Clin Chem. 2008;46:87--130

73. Spentzas T, Henricksen J, Patters AB, et al. Correlation ofintraocular pressure with intracranial pressure in childrenwith severe head injuries. Pediatr Crit Care Med. 2010;11:593--8

74. Steinbach GC, Macias BR, Tanaka K, et al. Intracranialpressure dynamics assessed by noninvasive ultrasound during30 days of bed rest. Aviat Space Eviron Med. 2005;76:85--90

75. Stenger MB, Brown AK, Lee SM, et al. Gradient compressiongarments as a countermeasure to post-spaceflight orthostaticintolerance. Aviat Space Environ Med. 2010;81:883--7

76. Tesch PA, Berg HE, Bring D, et al. Effects of 17-dayspaceflight on knee extensor muscle function and size.Eur J Appl Physiol. 2005;93:463--8

77. Trick GL, Vesti E, Tawansy K, et al. Quantitative evaluation ofpapilledema in pseudotumor cerebri. Invest Ophthalmol VisSci. 1998;39:1964--71

78. Tripathi RC. Ultrastructure of the arachnoid mater inrelation to outflow of cerebrospinal fluid. A new concept.Lancet. 1973;2:8--11

79. Wall M. Idiopathic intracranial hypertension. Neurol Clin.2010;28:593--617

80. Weinreb RN, Khaw PT. Primary open-angle glaucoma.Lancet. 2004;363:1711--20

81. Weinreb RN, Cook J, Friberg TR. Effect of inverted bodyposition on intraocular pressure. Am J Ophthalmol. 1984;98:784--7

82. Worgul BV. Cataract analysis and the assessment of radiationrisk in space. Adv Space Res. 1986;6:285--93

83. Xu X, Cao R, Tao Y, et al. Intraocular pressure and ocularperfusion pressure in myopes during 21 min head-downrest. Aviat Space Eviron Med. 2010;81:418--22

84. Zwart SR, Pierson D, Mehta S, et al. Capacity of omega-3fatty acids or eicosapentaenoic acid to counteractweightlessness-induced bone loss by inhibiting NF-kappaBactivation: from cells to bed rest to astronauts. J Bone MinerRes. 2010;25:1049--57

85. Zwart SR, Oliver SA, Fesperman JV, et al. Nutritional statusassessment before, during, and after long-duration head-down bed rest. Aviat Space Environ Med. 2009;80(Suppl 5):A15--22

Other Cited Material

A. Watkins SD, Barr YR. Papilledema summit: summary report.NASA Technical Report NASA/TM-2010-216114, S-1058.Available at: http://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/20100014176_2010013905.pdf. Accessed 26 July2011

B. Ansari RR, Manuel FK, Suh KI, et al. Choroidal blood flowmeasurements in zero gravity (space-like) environmentusing laser-doppler flowmetry [Abstract]. Association forResearch in Vision and Ophthalmology (ARVO) AnnualMeeting, Fort Lauderdale, FL, May 2003

C. Gibson R, Mader T, Caputo M, et al. Effects of microgravityand 2G on simultaneous intraocular pressure and retinalvessel caliber changes [Abstract]. Aerospace Medical Associ-ation Annual Scientific Meeting, NewOrleans, LA, May 1990

Reprint address: Gianmarco Vizzeri, MD, Department ofOphthalmology and Visual Sciences, The University of TexasMedical Branch, 301 University Blvd., Galveston, Texas 77555--1106. e-mail: givizzer@utmb.edu.

MICROGRAVITY AND VISUAL FUNCTION 163

Outline

I. IntroductionII. Ocular changes related to spaceflightIII. Head-down tilt bed-rest analogIV. Posture-induced ocular changes

A. Intraocular pressure and cardiovascularchanges

B. Ocular perfusion pressure and choroidalblood flow

C. Retinal blood vessels

V. Intraocular pressure and microgravity

VI. Intracranial pressure and microgravity

A. The effect of microgravity on intracranialfluid homeostasis

B. Intracranial pressure measurement inmicrogravity

VII. ‘‘Translaminar pressure’’ and optic nerve headabnormalities

VIII. ConclusionIX. Method of literature search