NASA Technical Reports Server (NTRS) 20150004101: Numerical Modeling of Ophthalmic Response to Space

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Numerical Modeling of Ophthalmic Response to Space
E.S. Nelson1, J.G. Myers1, L. Mulugeta2, J. Vera1, J. Raykin3, A. Feola3, R. Gleason3, B. Samuels4, and C.R. Ethier3
1NASA Glenn Research Center, Cleveland, OH
2Universities Space Research Association, Houston, TX
3Georgia Institute of Technology/Emory University, Atlanta, GA
4U. Alabama at Birmingham, Birmingham, AL
INTRODUCTION RESULTS
To investigate ophthalmic changes in spaceflight, we would like to predict the impact of Inresponsetoimposedvolumechanges,thelivingeyeincorporatesbothpassiveandactive
blooddysregulationandelevatedintracranialpressure(ICP)onIntraocularPressure(IOP). behaviors, such as regulation, while nonliving eyes can only show a passive response. We
Unlikeotherphysiologicalsystems,thereareveryfewlumpedparametermodelsoftheeye attributethedifferencebetweenthecurvesinFig2atobloodflowandbloodvolumechanges.
[1, 2]. The eye model described here is novel in its inclusion of the human choroid and Thecompliancebetweentheglobeandbloodcompartments,C ,atagivenIOPistheratioof
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retrobulbarsubarachnoidspace(rSAS),whicharekeyelementsininvestigatingtheimpact (cid:39)V toIOP(Fig3).Notethat C isoforder1(cid:80)L/mmHgatatypicalIOPof15mmHg.
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ofincreasedICPandocularbloodvolume.Someingenuitywasrequiredinmodelingthe Foradjacentcompartmentsthatdonotexchange
blood and rSAS compartments due to the lack of quantitative data on essential fluid, the compliance governs the extent to which
hydrodynamic quantities, such as net choroidal volume and blood flowrate, inlet and exit adjoining pressures can influence each other. To
pressures,andmaterialproperties,suchascompliancesbetweencompartments. calculate compliance between the rSAS and globe,
we used clinical data on LC location (Fig 2b) to
MATERIALSANDMETHODS
determine an areal change following IOP reduction
Themodeliscomprisedoffourcompartments(Fig1a).Duetothescarcityofdata,asingle andsweptthisarea180°toestimatevolumechange.
bloodcompartmentisaproxyforthevasculatureoftheeye.Wederivedanequationforthe WecalculatedthatCrg~1.1e-3(cid:80)L/mmHg.Sincethis
net arterial inflow Qa (Fig 1b) by drawing inspiration from prior works [3-5]. We have is three orders of magnitude lower than Cbg, we
assumedthattheretinaiswell-regulatedsothatitseffectonIOPchangescanbeignored. FFFcoiiigmurpea 333rt.m CCCeonmtps lllaiiiasn dceer ibbbveetdw feroenm t thhhhee g dllloifbbbfeer eanntdddi abbbllll oreosdddp onse pcoremdpicatritshoanttPocstfhpeladyysnaammicsinoofrbrlooloedinfloswe.tting IOPin
(a) ((bb)) CFNACLPbrOggAMENbrfAuSClxoAniLaodSAld-u tlT-seot Uno-pgg-uRlgtolhElsobabetie oc oncom ammpplpialilnaitncuecdee [4, 5] fbforeortmwI e[O6e]nP. livcinhga anngd eenu((cid:39)cleIaOtePd) eyines. pDaatraa obbotaliincedf lightasaFifgun4cptiroenseonftsineitxiapleIrOimPe0n.tMalaadnedrseitmaull.a[t8e]dsrheosuwletsd
HR heart rate large variation in inter-individual response as measured via TonoPen. The data points may
PICcsPf rinettrraoclaramniinaal rprpersessusruere representthemeanvalueofreplicatedmeasurements.Wehadinsufficientinformationtoinclude
IQQQQQRt(cid:68)cOgaatuvmPqv inatuvgctnhrhelqevaotinoeutrnbb aooreaneeoousoric inctcrsuduealug esalordal rlfiauhiaraatur tullcha f spmitalqinoocrqufekowrule*nsor es obewfuooulsorusrseom so doau uvttioftolflonluow mrwa e te fraction [3] emahrbeeroaoaTvlrtsehhuyerbewammsritsiihemdndutolpleaona-trariaodgtmneehvdeeiftcoemelrelosauxwlnpetsce.heraWirmttthaeeeirnneuttpaiaserllegsed.osderiaanthnttamaarddtiutefyiecfpiinaiceltalodyl
Choroidalblood flow (cid:39)(cid:39)VVbg vvoolluummee cchhaannggee ooff bgllooboed generated Qaas a sinusoidal forcing function and
allowedittodoubleinmagnitude.Wewereunable
Qa= (8/9)(cid:83)(cid:68)HR [(Rg-tc)3–(Rg-tc-FPA)3] toincorporatepossibleconfoundingfactors,suchas
Figure 1. Schematic of: (a) 4-compartment lumped parameter eye model; and (b) calculation of net choroidalflow. the effect of commonly used medications in
Researchershaveinjectedsalineintotheanteriorchamberoftheeyetostudyitseffecton parabolicflight.Thesimulationdoesnotincludeany
IOP.Fig2ashowsacompilationofsuchdataforthenetvolumechangeoftheglobe,(cid:39)V, explicit regulatory response nor does it attempt to
g
andIOPforenucleatedeyes(blue)andlivingeyes(red)[6].Fromthis,wecandetermine covertheentirevalidphysiologicalrange.Evenwith
Cbg.Parketal.[7]documentedthechangeinposition(xLC,yLC)oftheanteriorsurfaceofthe Figure 4. Changes in intraocular pressure during parabolic thissimpleframework,thesimulatedresultslargely
laminacribrosa(LC)resultingfromsurgicalinterventionforreliefofhighIOP(Fig2b).Unlike flight for experimental [8] and simulated results. fallwithintheexperimentalconfidenceinterval.
chronicglaucomapatients,theseindividualsexperiencedelevatedIOPforashorttime(here, Studiesofacuteocularbloodflow,e.g.,duetoexerciseorposturalchange,demonstratethat
2.57±1.32days).Itisunlikelythatsubstantialtissueremodelingcouldhaveoccurredover individuals may show a variety of regulatory responses. Our next challenge is to incorporate
thisrelativelybriefperiod,sowewillassumethatthechangeinLCpositionrepresentsan regulationanddemographicvariabilityintoourmodelinameaningfulway.
elasticresponseofthetissuesoftheposterioreye.
CONCLUSIONS
((aa)) (b)
We developed a means of computing compliances and flowrates for the rSAS and blood
compartment that are currently unavailable in the literature. The estimate of globe-to-rSAS
complianceisfarsmallerthanthatbetweentheglobeandbloodcompartment,indicatingthat
blooddynamicsismoreimportantthanretrolaminarpressureinsettingIOP.However,P still
csf
playsamajorroleinsettingthebiomechanicalstressstateintheLC.Preliminaryvalidationofthe
lumpedparametereyemodelproducedencouragingresults,whichsuggestthatthedependence
of C on IOP may play an important role in ocular response to acute hydrostatic pressure
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change.Followingadditionaldevelopment,verificationandvalidation,thiscodewillbeusedto
Fiigguurree 22. EEsssseennttiiaall ddaattaa ffoorr ddeetteerrmmiinniinngg ccoommpplliiaanncceess:: ((aa)) PPrreessure/volume curve for the globe in living (red) and enucleated (blue) systematicallyexploretherelativeimportanceofeachflowcomponent,compartmentpressure,
eyes. (Data derived from [6]) and; (b) the change in position of the lamina cribrosadue to surgical intervention for IOPreduction. complianceandresistancethroughouttherelevantphysiologicalranges.
(Data derived from [7])
ACKNOWLEDGEMENTS
This work was funded by NASA’s Human Research Program by the Digital Astronaut Project (DAP) and grant number NNX13AP91G. Thanksto DeVonGriffin for managing the DAP work and coordinating the NRA team.
REFERENCES
[1] Kiel, JW, et al. Progress in Retinal and Eye Research 30: 1-17 (2011). [2] Guidoboni, G, et al. Invest OphthalmolVis Sci55:4105-18 (2014). [3] Kiel, JW. ExptEye Res 1994 58:529-543. [4] Berisha, F et al. ActaOphthalmologica88:766-772 (2010) [5] Kiss, B et al. MicrovascRes 61:1-13
(2001). [6] Silver, DM and O Geyer. CurrEye Res 20:115-20 (2000). [7] Park, HY, et al. Invest OphthalmolVis Sci55:233-239 (2014). [8] Mader, TH et al. Am J Ophthalmol115:347-350 (1993).