Fogarty, Jennifer

NASA Technical Reports Server

Space Physiology 
Human Health and Performance Academy Lecture 
Visual Impairment and Intracranial Pressure  (VIIP): 
What is it and what does it tell us about 
Spaceflight Physiology? 
Jennifer Fogarty, PhD 
Clinical Translational Scientist 
Space and Clinical Operations Division 
Human Health and Performance Directorate 
January 17, 2013 
https://ntrs.nasa.gov/search.jsp?R=20130008754 2019-08-30T23:50:53+00:00Z
Contributors 
• Christian Otto
• Dave Francisco
• JD Polk
• Ashot Sargsyan
• Doug Hamilton
• LSAH - epidemiology
• BDRA – increment roll up
• HRP HHC Element
• VIIP RCAP
• VIIP IWG
2 
Agenda 
• Duration of Spaceflight
• Historical Context
• Spaceflight Physiology
• Data Collected
• Countermeasures
• Transition to Operations
• Visual Impairment and
Intracranial Pressure
– Incidence
– Vascular, Central Nervous,
Ocular components
– Cardiovascular Physiology
Refresher
– Fluid shift
– Imaging of the Eye and
Evidence
– Theory - ICP
– Clinical Practice Guideline
3 
Human Spaceflight Experience: 
The Long and the Short of it… 
Characteristics of the Vehicle 
Habitat Environment 
Partial Gravity Exposure 
Countermeasure Availability 
Physiological, Medical, Environmental Data 
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Historical Perspective 
• Gemini 5 (8 day mission) 
– Visual Tester in-flight 
– Visual acuity 
measurement program  
– Large rectangles at 
ground sites in Texas and 
Australia.  
– No changes noted in 
astronaut visual acuity 
postflight.  
– Duntley et al, 1966 
• Apollo  
– Retinal vascular 
photography reveals 
retinal vessels 
“decreased in size” at 3.5 
hours into flight.  
– 100% oxygen 
atmosphere 
– No visual acuity changes 
– Hawkins and 
Zieglschmid, 1975 
 
5 
Shuttle 
• 10-14 day missions
• Anecdotal reports of
vision changes, but
return to baseline.
• 1 astronaut with
bilateral lens implants
• No optic disc edema
cases, but an occasional
choroidal fold.
• 122 crewmembers
between 1995 and
1998, 15% indicated
decrements in near
vision on orbit. Returns
to baseline.
• Paloski et al 2008
6 
Differences Between 
Historical and Present 
• Missions were 5 to 17 days
generally (Skylab a notable
exception)
• Astronaut age was mean of
38
• MRI and OCT not available
• Spacecraft ranged from 5.0
psi to 10.7 psi to 14.7 psi
with varying oxygen
concentrations
• Missions average 6 months
on ISS
• Astronaut mean age 46.7
• MRI, OCT, Telemedicine
fundoscopy
• 14.7 psi, 21% oxygen
• Robust exercise suite
7 
Human Response to Spaceflight 
•Muscular 
•Cardiovascular  
Astronauts experience a 
spectrum of adaptations in 
flight and post flight  
Balance disorders 
Cardiovascular deconditioning 
Decreased immune function 
Muscle atrophy 
Bone loss 
 
•Neurovestibular 
•Behavioral 
•Immunological 
•Nutritional 
•Skeletal 
Exposures: 
 
Launch & Landing 
Loads 
 
Microgravity 
 
Closed Environment 
(air and water) 
 
Confined Habitat 
 
Radiation Exposure 
 
Time Course of Physiological Changes  
During Weightlessness 
· Neurovestibular System 
r· 11·Juids and Electro~yt~ . Card10vascular System Clinical 
HoJizon 
0-g 
Set 
Point i--7 ,,~ ,._-::=:;;a~ ~ 
1-g 
Set 
Point 
Time Scale (Months) 1 
Red Blood CelJ Mass 
Bone and Calcium Metabolism 
r Lean Body Mass 
3 4 5 
Point of Adaptation 
6 
Physiological & Psychosocial Manifestations  
Associated with Space Flight  
 
Bone 
 Bone mineral content 
 Bone mineral density 
 Urinary calcium 
 Renal stone risk 
Skeletal Muscle 
 Skeletal muscle mass 
 Skeletal muscle strength 
 Skeletal muscle endurance 
 Skeletal muscle capillary 
density 
Neurosensory 
 Vestibular disturbances 
 Space motion sickness 
 Sensorimotor function 
 Postural & locomotor 
stability 
GI/Pharmacokinetics 
 GI motility and PK 
 
Cardiovascular 
 Fluid volume 
 Orthostatic tolerance 
 Aerobic capacity 
 Arrhythmias 
Psychosocial 
 Team issues 
 Confinement issues 
 Fatigue 
 Stress 
 Errors 
 Cognitive Function 
Environmental 
 CO2 (2-5 mmHg)* 
 Hearing loss due to 
acoustics 
 Radiation exposure 
 Risk of cataracts/cancers 
 Skin irritations due to 
microbial growths 
Biomedical Data 
• Data Collected via Medical Requirements
• Assessments of:
– Bone
– Cardiovascular
– Aerobic Fitness
– Sensory Motor
– Functional Fitness
– Nutritional Status
12 12 
International Space Station 
BMD % Change from Preflight 
Expeditions 1-16 (n=20)
-30.0
-25.0
-20.0
-15.0
-10.0
-5.0
0.0
5.0
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Spine
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Neck
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Body
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Days-After-Landing
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(%
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B
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 C
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(%
)
Pelvis 
Loss0=7.7%    Recovery Half-life=97 d 
Percent Change in Estimated VO2 Index from Pre-Flight Expeditions 1-16 (n=20)
-40
-30
-20
-10
0
10
20
30
40
50
0-29 30-69 70-99 100-129 130-149 150+ R+4-7 R+30-35
%
 c
ha
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fr
om
 p
re
-fl
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ht
Medical Requirements collect physiological, medical and environmental data 
Data can be used to assess the individual 
or the population 
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Postftight Functional Fitness Expeditions 1-16 (n=20) 
R+5 R+J0 
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Cortical Bone/ “Compact Bone” 
Sources:  L. Mosekilde; SL Bonnick; P Crompton 
PROXIMAL FEMUR 
VERTEBRAL BODY 
Cancellous “Spongy” Bone/Trabecular Bone 
Trochanter 
Femoral 
Neck 
Bone compartments or bone types 
An example of a spaceflight adaptation that is well described but still lacks understanding 
of time course, recovery, and long term risk 
 = Nominal  availability = Restricted use = No  availability
TVIS
I-RED
CEVIS
ISS Exercise Hardware Availability Timeline
I-RED
Assembly
EXP1 EXP2 EXP3 EXP4 EXP5 EXP6 EXP7 EXP8 EXP9
CEVIS 
Assembly
TVIS 
Assembly
restricted to 
arm ergometry
failing control 
panel
EXP10
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replaces I-RED
EXP12EXP11
10/00 09/0506/02 10/03 04/0510/0404/0311/0203/01 12/0108/01 04/04
EXP13 EXP14 EXP15 EXP16
03/06 09/06 04/07 10/07
CCC 
Installed
failed control 
panel; CCC 
installed
DC power 
converter 
failure
7th fwd stbd roller 
deteriorated
Incorrect thimble 
on new cord
Countermeasures 
Operational Research 
• .., 
• II 
• ~ ---
A consequence of human spaceflight 
• Visual Impairment and Intracranial Pressure (VIIP)
• What is the problem?
– Optic Disc Edema, Globe Flattening, Choroidal Folds, Hyperopic Shifts and Raised Intracranial
Pressure has occurred in Astronauts During and After Long Duration Space Flight
• What is the risk?
– Given that all astronauts experience a microgravity-induced cephalad fluid shift and that
both symptomatic and asymptomatic individuals have exhibited optic nerve sheath edema
on MRI, there is a high probability that all astronauts have some degree of idiopathic
intracranial hypertension. Those that are susceptible (due to eye architecture, anatomy,
narrow disc, etc.) have a high likelihood of developing either choroidal folds or papilledema,
and the degree of edema will determine impairment and long-term or permanent vision loss.
A consequence of human spaceflight 
• Visual Impairment and Intracranial Pressure (VIIP)
– Operational processes (medical requirement) put in
place to diagnose and manage 2008 (fundoscope and
eye ultrasound)
– Sentinel case found retrospectively (2005; Exp 11)
– Integrated approach kicked off to address the issue: 2010
– Research and Clinical Advisory Panel formulated in 2011
– Occupational Health Research Protocol developed 2012
– 9 Studies funded in 2012
18 
Vision Impairment & Intracranial Pressure Risk Update 
Incidence Rate 
Incidence rate of VIIP per the CPG classifications 
36 long duration US astronauts 
21 Evaluated as of 7/2012 
42% 
29% 
10% 
38% 
5% 
19% 
0 
5 
10 
15 
20 
Not Evaluated Class 0 Class 1 Class 2 Class 3 Class 4 
N
um
be
r o
f C
as
es
 
CPG Classification 
N=15 N=6 N=2 N=8 N=4 N=1 
These crewmembers did not have MRIs, OCTs or 
cycloplegic refraction – NASA is in the process of 
obtaining this information/evaluation 
Refractive changes ≥ .50 diopter cycloplegic 
refractive change and/or cotton wool spot 
Choroidal folds and/or ONSD and/or 
globe flattening and/or scotoma 
Optic Disc Edema 0-2 
Optic Disc Edema 3-4 
+ 
+ 
21 crew members have been evaluated 
15 have symptoms – 15/21 = 71% 
Class 3 and 4 – 5/21 = 24% 
I 
I 
1. The Vascular System 2. The Brain 3. The Eye
+ + 
VIIP: A Three-Part Story 
Intraocular pressure 
Corneal Thickness 
Visual acuity (Pre/In/Post) 
Refractive error (Pre/Post) 
Optic Disc:Cup ratio (Pre/Post) 
OCT (Pre/Post) 
RNFL 
RPE angle 
Optic nerve head 
Choroidal Folds 
High Res Retinal Photography 
Retinal hemorrhages 
Cotton wool spots 
Optical Biometry (Pre/Post) 
Globe axial length 
MRI Intracranial (Pre/Post) 
Peak CSF flow 
CSF Production 
Glove Flattening 
Globe Axial Length 
Optic Nerve Tortuosity 
Ultrasound (Pre/In/Post) 
ONSD 
Nerve/Sheath Ratio 
Environmental  
CO2 Levels 
Demographic 
Gender 
Age  
Race 
Body Composition 
Height 
Weight 
% Lean Body Mass 
%Fat Body Mass 
Cardiac 
Resting Blood pressure 
Resting Cardiac output 
Biochemistry 
Homocysteine 
Lipids (LDL, HDL, TGs) 
Serum Insulin 
HbA1c 
Fasting serum glucose 
Fitness 
MVO2 (max oxygen uptake) 
19 
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20 
ffden-2.phys.uaf.edu 
webschoolsolutions.com 
 
Blood Vessel Compliance 
Starling Equation:  
hydrostatic and oncotic forces (the so-called 
Starling forces) in the movement of fluid 
across capillary membranes 
Cardiovascular Physiology Background 
http://en.wikipedia.org/wiki/Starling_equation#cite_note-1 
Venous compliance is approximately 30 
times larger than arterial compliance 
Tissue capillaries 
l 
Vein-----i 
LUNGS----• 
Vein ___ _ 
Venules 
Tissue capillaries 
Pulmonary artery 
Pulmonary vein 
f----- Artery 
---Arterial circulation 
___ Venous circulation 
The Starling equation reads as fo llows: 
1/16/2013 21 
Fluid Shifts during Space Flight 
On Earth, gravity 
exerts a 
downward 
force to keep 
fluids flowing 
to the lower 
body.  
In space, the fluid tends to 
redistribute toward the 
chest and upper body. At 
this point, the body 
detects a “flood” in and 
around the heart.  
The body rids itself of this 
perceived “excess” 
fluid.  The body 
functions with less fluid 
and the heart becomes 
smaller.  
Lu
ja
n 
an
d 
W
hi
te
 (1
99
5)
 
Upon return to 
Earth, gravity 
again pulls the 
fluid 
downward, but 
there is not 
enough fluid to 
function 
normally on 
Earth. 
Lujan and White (1995) 
.. 
.. 
a 
C 
✓ 
d 
-2
7-9
X 
0G 
Redistribution of Venous Pressures 
From 1G to 0G 
• Cranium is rigid
• Venous congestion
• Obligate arterial flow
• Transcapillary leak
• ++ICP~30-40
9.8m/s2 
15-20
3. Chapman et al. The Relationship between Ventricular Fluid Pressure and Body Position in Normal Subjects with Shunts. Neurosurgery 1990
1. Hirvonen et al.  Hemodynamic changes due to Trendelenburg positioning and pneumoperitoneum during laproscopic hysterectomy, Acta  Anaesthesiologica Scandiavica. 1995 
4. Gisolf  et al. Human cerebral outflow pathway depends on posture and central venous pressure. Journal of Physiology, 2004.
2. Hinghofer-Szalkay  Gravity, the hydrorostatic indifference concept and  the cardiovascular system. European Journal of Applied Physiology, 2010
Standing 1G 
0 
0 
20 
40 
60 
80 
100 
Integrated Vision Impairment & Intracranial Pressure Project 
Risk Background - Symptoms 
MRI Orbital 
Image 
showing 
globe 
flattening 
Normal Globe Flattened Globe 
•Choroidal Folds
parallel grooves in
the posterior pole
•Globe Flattening
•Optic Disc Edema (swelling)
•Altered Blood flow
“cotton wool” spots
•Hyperopic Shifts
-Up to +1.75 diopters
•Increased Optic
Nerve Sheath Diameter
23 
ICP 
•Scotoma
Altered/Disrupted 
Visual Field 
Background: 
•15 known “clinical cases” (of 36 long duration crew members)
•Each with different degrees of symptoms
•Does not currently include data from international partners
•Current assessment of  Russian participation underway
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Normal Globe Flatten Globe 
•Globe Flattening •Increased Optic Nerve
Sheath Diameter
•Optic Disc Edema
(swelling)
1. Fluid Shift due to Microgravity 2. Fluid shift causes increased
intracranial pressure (ICP) (?)
•Hyperopic Shifts
-Up to +1.75 diopters
•Choroidal Folds
parallel grooves in the
posterior pole
Current Hypothesis 
24 
3. ICP transmitted to optic nerve and eye
+ICP
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Potential for Serious Functional Impairment: 
Image can be located at :  
http://medical-dictionary.thefreedictionary.com/hyperopia 
Scotoma Hyperopia 
Changes in visual acuity are 
assessed with regular vision 
testing on orbit 
-.:s-
Hyperopia, or far s iglht edness, is a condit ion of the eye w her,e inooming1 rays 
of light impinge on the retina befo re conver ging int o a focused image, 
r,esulting1 in d ifficulty seeing nearby objects c lear ly. 
(Illustration by Electronic Illustrators Group.) 
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26 
VIIP- Hardware 
On –Orbit Ocular Measures 
Choroidal 
Folds -
parallel 
grooves in 
the back of 
the eye 
Optic Disc Edema
Altered Blood flow 
“cotton wool” spots 
Postflight OD 
Postflight OS Inferior Superior 
Inferior Superior 
•Ultrasound is used to track optic nerve sheath diameter and
globe flattening pre-, in-, and post flight
•Current fundoscope (PanOptic) can not detect choroidal folds
•New Hardware:
•Fundoscope with better resolution (ISS CR Approved June 2012)
•Will give qualitative data
•Optical Coherence Tomography (OCT)
•Will give quantitative data: progression of choroidal
folds and nerve fiber layer changes
Optical Coherence Tomography (OCT) measures 
Increased Optic  
 Nerve Sheath Diameter 
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Key Brain Areas Potentially Affected by Fluid Shift 
CSF Production 
CSF Resorbtion 
(AG-Venous/Lymphatic) 
Venous Congestion 
Interstitial fluid 
The Brain is an Expansile Vascular Organ Within  
a Rigid Cranium: An swollen brain can impair blood flow to itself 
Expanding Brain Parenchyma & Cerebellum 
Compresses Transverse Sinus 
Great cerebral vein of Gale n 
Superior sagittal sinus 
------
30 
Vision Impairment & Intracranial Pressure Risk Update 
Case Definition for Spaceflight-Induced Intracranial Hypertension 
Class 0 
• < .50 diopter cycloplegic
refractive change
• No evidence of
papilledema, nerve sheath
distention, choroidal folds,
globe flattening, scotoma
or cotton wool spots
compared to baseline.
Class 1 
• Refractive changes ≥ .50
diopter cycloplegic
refractive change and/or
cotton wool spot
• No evidence of papilledema,
nerve sheath distention,
choroidal folds, globe
flattening, scotoma
compared to baseline.
• CSF opening pressure (if
measured) ≤ 25 cmH2O
Class 2 
• Class 1 plus:
• Choroidal folds and/or optic
nerve sheath distension and/or
globe flattening and/or 
scotoma 
• No evidence of papilledema
• CSF opening pressure ≤ 25 cm
H2O (if measured)
Treatment: Repeat OCT, cycloplegic 
refraction, fundus exam and threshold visual 
field every 4 -6 weeks x 6 months, repeat 
MRI in 6 months   
Class 3 
• Class 2 plus:
• Papilledema of Grade 0-2.
Treatment: repeat OCT, cycloplegic refraction, fundus 
exam and threshold visual field every 4 -6 weeks x 6 
months, repeat MRI in 6 months 
Class 4 
• Class 3 plus:
• Papilledema Grade 2 or above.
• Presenting symptoms of new headache, pulsatile
tinnitus and/or transient visual obscurations
• CSF opening pressure >25 cm H2O
Institute treatment protocol as per CPG – LP, repeat MRIs, 
pharmaceutical intervention 
Least Severe Symptoms 
Treatment: repeat OCT & visual acuity 
in 6 weeks 
Most Severe Symptoms 
L-90/45 daysAcceptable up 
to L-365 days 
Ultrasound 
Eye/Orbit 
MRI 
Of Brain and Orbits 
Without Contrast 
Fundoscopy -
PanOptic 
Ophthalmoscope 
Tonometry 
Visual Acuity 
Including Amsler Grid 
Testing 
Other  Tests - 
biomicroscopy (slit 
lamp), high resolution 
retinal photography, 
OCT (high resolution), 
and A-Scan.  
Preflight Exams 
Ultrasound 
Eye/Orbit 
MRI 
Of Brain and Orbits 
Without Contrast 
Fundoscopy -
PanOptic 
Ophthalmoscope 
Tonometry 
Visual Acuity 
Including Amsler Grid 
Testing 
Other  Tests - 
biomicroscopy (slit 
lamp), high resolution 
retinal photography, 
OCT (high resolution), 
and A-Scan.  
Ultrasound 
Eye/Orbit 
Fundoscopy -
PanOptic 
Ophthalmoscope 
Tonometry 
Visual Acuity 
Including Amsler Grid 
Testing 
L+30 & R-30,  
L+100 if requested  
(+/- 7 days) &  
as clinically indicated 
In-flight Exams Post flight Exams 
L+30 L+100 R-30L-90/45L-365
R+1 to R+3 
(or as soon as possible) 30, 90, 
180, 365 
 
R+1 to R+3  
Integrated Pre/In/Post-Flight VIIP Medical and Research Testing 
L+60L+10
Ultrasound 
Eye/Orbit 
Fundoscopy -
PanOptic 
Ophthalmoscope 
Tonometry 
Visual Acuity 
Including Amsler Grid 
Testing 
Blood 
Pressure 
Vascular 
Compliance 
L+10, 30, 60, 100 
& R-30,  
(+/- 7 days) 
Research 
Medical Ops 
31 
New Research 
Protocol 
Vascular 
Compliance 
R+365 R+180  R+90  R+30  
.----
.__ ____ _ 
Clinical Implications 
• Potential disability
secondary to vision loss in
astronauts susceptible to
optic disc edema or
choroidal folds
• Potential for long-term
sequelae due to optic nerve
cells ischemia (visual field
defect or loss)
• Potential effect on white
matter (senility, dementia,
etc.)
• Decreased functional ability
due to IIH
• Unknown contribution to
space motion sickness,
asthenia, or functional
impairments
• Potential to worsen with
repetitive flights or long
term space missions
2/7/2011 UNCLASSIFIED 32 
Questions? 
33 NIOSH 9/17/2012 


Visual Impairment and Intracranial Pressure (VIIP): What Is It and What Does It Tell Us About Spaceflight Physiology?

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