Modeling the Effects of Spaceflight on the Posterior Eye in VIIP

C. R. ETHIER, A.J. FEOLA, J. RAYKIN, L. MULUGETA, R. GLEASON, J.G . MYERS, E.S. NELSON, AND B. SAMUELS

W W W. E T H I E R L A B . G AT E C H . E D U

https://ntrs.nasa.gov/search.jsp?R=20150011647 2018-05-24T18:25:30+00:00Z

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Commercial Relationships Disclosure

No relationships to disclose for any co-author

2

Funding support

o NASA Grant NNX13AP91G

o Georgia Research Alliance

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VIIP Syndrome Permanent changes in visual function/ocular anatomy after long-duration space flighto 41.7% incidence in U.S. astronauts

o Choroidal folds, papilledema, globe flattening, optic nerve dura distention/kinking

Kramer et al. Radiology, 2012.

Normal Astronaut with VIIP

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Hypothesis

Increased intracranial pressure (ICP) due to cephalad fluid shift

leads to:

o Connective tissue remodeling in the posterior eye/optic nerve sheath

o Mechanical loading/insult to ONH cells and tissues, and eventual vision loss

humanresearchroadmap.nasa.gov

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Goal

Study the biomechanical response of the optic nerve sheath and posterior eye to changes in ICP

o Account for different ICP “cases”o Terrestrial supine

o Terrestrial standing

o Microgravity (presumed elevated ICP)

o Account for variations of ICP within these cases

o Account for variations in tissue properties

MethodsCOMPUTATIONAL (FINITE ELEMENT) MODEL

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ScleraRetinaPeripapillary

Sclera

DuraMater

PiaMater

CentralRetinalVessel

Axis of Rotation

OpticNerve

Lamina Cribrosa

Model Geometry

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Name Abbreviation Units BaselineStandard Deviation

Low High

Pressures

Intraocular Pressure IOP mmHg 15 1.85 10 19

Intracranial Pressure ICP mmHg

Upright 0 2.0 -4 4

Supine 10 2.0 6 14

Elevated 20 2.5 15 25

Mean Arterial Pressure MAP mmHg 86 7.96 60 112

Biomechanical Properties

Sclera Young’s modulus SC MPa 5 1 9

Peripapillary Sclera Young’s modulus ppSC MPa 5 1 9

Lamina Cribrosa Young’s modulus LC MPa 0.5 0.1 0.9

Pia Mater Young’s modulus Pia MPa 5 1 9

Dura Mater Young’s modulus Dura MPa 1 0.2 2

Optic Nerve Young’s modulus ON MPa 0.05 0.01 0.09

Retina Young’s modulus Ret MPa 0.05 0.01 0.09

Retinal Vessel Young’s modulus RV MPa 0.3 0.2 0.4

Neural Poisson’s ratio Poisson’s - 0.45 0.4 0.49

Model Inputs

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Latin hypercube samplingEfficiently simulates variation in input parameters (Monte Carlo)

Intracranial Pressure (mmHg)

Mean Arterial Pressure (mmHg)

Intraocular Pressure (mmHg)

12 14 16 18

60 80 100

-5 5 15 25

Upright Supine Elevated

0 5 10ONH Material Properties(SC, ppSC, LC, Pia, Dura, ON,

Ret, RV and Poisson’s)

Upright Supine Elevated

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Outcome measure

Strain in ONH tissueso Physical quantity that represents stretching of

cells and tissues

o Local cells are mechanoresponsive

o Strain drives connective tissue remodeling in many other tissues, e.g. artery walls

ResultsCOMPUTATIONAL (FINITE ELEMENT) MODEL

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ICP: 0 mmHg ICP: 10 mmHg ICP: 20 mmHg

1st Principal Strain

(Stretch)

3rd Principal Strain

(Compression)

2.0%

-2.0%

Effect of ICP: Baseline case

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Average strains: Baseline case

Tissue Region: Lamina Cribrosa Optic Nerve Retina

Strain Type: Tension Compression Tension Compression Tension Compression

ICP = 0 mmHg 0.57% -0.86% 0.61% -0.85% 0.35% -0.48%

ICP = 10 mmHg 0.78% -1.11% 0.78% -1.21% 0.63% -0.83%

ICP = 20 mmHg 0.97% -1.35% 0.96% -1.56% 0.91% -1.21%

Regions of Interest: Retina

Lamina Cribrosa

Optic Nerve

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Lamina Cribrosa Strain Histograms

TensionCompression

0

300

600

900

-1.00% -0.50% 0.00% 0.50% 1.00%

Pro

bab

ility

Den

sity

Est

imat

e

Strain

1st Principal Strain3rd Principal Strain

5th Percentile

95th Percentile

Denote 5th and 95th

percentile values as “Peak strains”

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Distribution within population

0% 5%1% 2% 3% 4%

Use Latin Hypercube Sampling

Peak strain in LC

Histogram

Cumulative Distribution

100%

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0

0.2

0.4

0.6

0.8

1

-4% -2% 0% 2% 4%

Cu

mu

lati

ve P

rob

abili

tyUpright ICPSupine ICPElevated ICP

“Peak” Strains in Lamina Cribrosa

TensionCompression

0

0.2

0.4

0.6

0.8

1

-4% -2% 0% 2% 4%

Cu

mu

lati

ve P

rob

abili

ty

0

0.2

0.4

0.6

0.8

1

-4% -2% 0% 2% 4%

Cu

mu

lati

ve P

rob

abili

ty

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0

0.2

0.4

0.6

0.8

1

-4% -2% 0% 2% 4%

Cu

mu

lati

ve P

rob

abili

tyUpright ICPSupine ICPElevated ICP

“Peak” Strains in Retina

TensionCompression

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0

0.2

0.4

0.6

0.8

1

-4% -2% 0% 2% 4%

Cu

mu

lati

ve P

rob

abili

tyUpright ICPSupine ICPElevated ICP

“Peak” Strains in Optic Nerve

5%

20%

TensionCompression

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“Out of this World Strains”

Tissue Region: Lamina Cribrosa Optic Nerve Retina

Strain Type: Tension Compression Tension Compression Tension Compression

Supine 8% 5% 20% 6% 10% 13%

Percentage of individuals with elevated ICP experiencing strains larger than those experienced under terrestrial conditions (standing or supine)

Optic Nerve SheathEXPERIMENTAL MEASUREMENTS

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Collagen orientation in duraSHG microscopy images of dura

0 mm Hg 10 mm Hg

Nerve Axis Nerve Axis

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Optic nerve has slack

Liu et al., BJO, 1992

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What is state of ON stretch?

Perform craniotomy

Expose orbit

Remove periorbital tissue

covering the optic nerve

Place markers on the optic

nerve

Transect nerve and record

axial retraction

Expose optic nerve, transect, observe retraction (or not)

http://www.dcfirst.com/pig_anatomy_poster.html

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Optic nerve retraction

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Summary

ICP affects strains in ONH tissues:◦ Average strain values are low

◦ Simulation of “population” shows that 5-20% of individuals will experience ICP-induced strains in space that are more extreme than those on earth

Uncertainties/Limitations◦ Optic nerve appears to be under tension (?!)

◦ Some tissue properties still not well understood

◦ Pathophysiology of vision loss and connection with strain not established

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BME at Georgia Tech/Emory