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BLOOD FLOW IN GLAUCOMA – INSIGHTS AND PERSPECTIVES

Leo Semes, OD Professor Emeritus of Optometry and Vision Science, UAB

California Optometric

Association Monterey 2018

Disclosures–LeoSemes,OD,FAAOCommercial Interest

Nature of Relevant Financial Relationship

Maculogix Honorarium Speaker Science Based Health Honorarium Speaker OptoVue Honorarium Speaker B&L Honorarium Advisor Allergan

Regneneron

Shire

ZeaVision

Reichert/Ametek

HPO

Honorarium

Honorarium

Honorarium

Honorarium

Honorarium

Stock options

Advisor

Speaker

Speaker

Advisor

Speaker

Advisor

DavidSackett,MD[1934-2015]

•  Widelyregardedasthefatherofevidence-basedmedicine.

Halfofwhatyou'lllearnduringtrainingwillbeshowntobeeitherdeadwrongorout-of-datewithin5years...;…thetroubleisthatnobodycantellyouwhichhalf.

OcularBloodFlowandglaucoma?Stateofthescience2009

“Atthepresenttime,noSINGLEbloodflowimagingdeviceiscapableofevaluatingocularbloodflowrelevanttoglaucoma.

“Acomprehensiveapproach,utilizingmultipleimagingtechnologiesisrequiredformeaningfulinsightintothemultiplevascularbedsoftheeye.”

Consensusstatement

oftheWGA2009

Howmanystateshaveonlyfourletters?

•  Clue:Ohioisnotone

Seriously...

POAGisaprogressive,chronicopticneuropathyinadultsinwhichintraocularpressure(IOP)andothercurrentlyunknownfactorscontributetodamageandinwhichthereisacharacteristicacquiredatrophyoftheopticnerveandlossofretinalganglioncellsandtheiraxons.Thisconditionisassociatedwithananteriorchamberanglethatisopenbygonioscopicappearance.–alaAAOPPP

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Seriously...POAGisaprogressive,chronicopticneuropathyinadultsinwhichintraocularpressure(IOP)andothercurrentlyunknownfactorscontributetodamageandinwhichthereisacharacteristicacquiredatrophyoftheopticnerveandlossofretinalganglioncellsandtheiraxons.Thisconditionisassociatedwithananteriorchamberanglethatisopenbygonioscopicappearance.–alaAAOPPP“Canglaucomatousopticneuropathybeinducedbyaprimarynon-IOP-relatedinsult...alone??”-ClaudeBurgoyne DX: POAG, ??? Is there a blood-flow problem here???

Maybeagoodintroduction

Whendoyouthinkthiseditorialappeared?

Maybeagoodintroduction

2009

OcularBloodFlowandglaucoma?Stateofthescience2009

“Atthepresenttime,noSINGLEbloodflowimagingdeviceiscapableofevaluatingocularbloodflowrelevanttoglaucoma.

“Acomprehensiveapproach,utilizingmultipleimagingtechnologiesisrequiredformeaningfulinsightintothemultiplevascularbedsoftheeye.”

ConsensusstatementoftheWGA2009

40o3DEnFaceReference

WideFieldEnfaceOCTTM

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OptovueWidefield-EnfaceOCT

WidefieldVS6mmx6mm3D

Multi-layerassessmentofpathology–evenintheperiphery

OptovueWidefield-EnfaceOCT SLO/LSLO2DImage

Choroidenface ChoroidTopographicalview

Widefield3DOCTVSWidefieldSLO

ILMenface ILMTopographicalview

Multi-layerassessmentofpathology–evenintheperiphery

IPLenface IPLTopographicalviewRPEenfaceRPETopographicalview

OCTwillrevolutionizethediagnosis,management&understandingofglaucoma…

• Higherresolution•  Differentialdepthscans• O/Rapplications•  Smartphoneapp•  OCTangiography!!!

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XRAvantiMCTwithOCTA1

OCTEnfaceimageSSADA/OCTAImagingSSADA/OCTAImaging

Flowratedirectlyrelatestoappearance(brightness)ofvesselintheimage2

*ImagescourtesyofDavidHuang,M.D.OHSU.

1OCTA(SSADA)isnotyetcommerciallyavailable.

Detailedvasculatureofthefovea

withoutanydyeorcontrast

enhancementinjection

Most anterior slab

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X-sect through macula-ONH axis

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note area above ONH with demonstrable RPE loss and prominence of choroidal vasculature. AND, absence of superficial as well as deep retinal capillary plexuses Compare with OCT X-section showing thinned retina.

2014

2014

Glaucoma

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Generalizedandlocaleffects....

CAPILLARY DENSITY AND RNFL THICKNESS COMPARISON

33 POAG pts. with VF depressions unilaterally *MD = -3.91 +/- 3.09 and normal fellow eye (MD = -0.2 +/- 0.9)

•  whole image vessel density (wiVD),

•  circumpapillary vessel density (cpVD), and

•  parafoveal vessel density (pfVD) Mean wiVD in unaffected eyes of patients with POAG was higher than in their fellow affected eyes but lower than in healthy eyes (P < 0.001). Mean circumpapillary RNFL (cpRNFL) thickness, mGCC thickness were also higher than those measurements in fellow eyes. “OCT-A measures detect changes in retinal microvasculature before VF damage is detectable in patients with POAG, and these changes may reflect damage to tissues relevant to the pathophysiology of glaucoma.”

Yarmohammadi A, et al. Peripapillary and Macular Vessel Density in Patients with Primary Open-Angle Glaucoma and Unilateral Visual Field Loss. Ophthalmology. Volume 125, Issue 4, April 2018, Pages 578-587

CHOROIDAL MICROVASCULAR DROPOUT (FOCAL SECTORAL CAPILLARY DROPOUT WITH NO VISIBLE MICROVASCULAR NETWORK IDENTIFIED IN THE CHOROIDAL LAYER)

32 Patients with an initial parafoveal scotoma (IPFS) within a 10° radius in 1 hemifield and, 42 POAG patients with an initial nasal step (INS) within the nasal periphery outside 10° of fixation in 1 hemifield. Microvasculature dropout (MvD) was observed in 25 of 32 eyes (78.1%) in the IPFS group, but in only 1 of 42

eyes (2.4%) in the INS group (P < 0.001). “The presence of MvD in the parapapillary choroid was a strong predictor for IPFS.”

Lee EJ, et al. Central Visual Field Damage and Parapapillary Choroidal Microvasculature Dropout in Primary Open-Angle Glaucoma Ophthalmology Volume 125, Issue 4, April 2018, Pages 588-596.

ANGIOANALYTICS APPROVED JUNE 2018

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2014

Maybethishelpsexplaintheasymmetrythatissoprevalentinglaucoma.Think:VF,rimtissue,PPA....

2012

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Proposedmechanisms

ReducedbloodflowcouldbeaconsequenceofneuraltissuelossarisingfromelevatedIOP

Proposedmechanism

ReducedbloodflowandelevatedIOPcouldbothleadtoneuralstructureloss

Proposedmechanism

ReducedbloodflowcouldbeanindependentcauseofVFloss

Andmoreevidence…

•  AstudyfromaregistryinEnglandsuggestedanassociationbetweenglaucoma*andvasculardementia*butnotbetweenglaucomaandAlzheimerdisease*.

•  [*Alzheimerandvasculardementiaarebothneurodegenerativediseasesandglaucomaisnowbeinglumpedintothatbucket,too.]

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KeenanTD,GoldacreR,GoldacreMJ.Associationsbetweenprimaryopenangleglaucoma,Alzheimer'sdiseaseandvasculardementia:recordlinkagestudy.BrJOphthalmol.2015Apr;99(4):524-7.

Perfusion

Pressure Blood Pressure

IOP

Lower Diastolic, Systolic, or

Mean Pressure Reduces Perfusion

Pressure

Higher IOP

Negatively Impacts Perfusion Pressure

Perfusion Pressure Is a Result of

A Delicate Balance Between IOP

and Blood Pressure

Lower Perfusion Pressure Is Associated with Increased Risk for

Open Angle Glaucoma Leske MC, et al. Ophthalmology  2007; 114,: 1965-72 Leske MC, et al. Ophthalmology 2008;115, 65-93.  Hayreh SS. Trans Am Acad Ophthalmol 1974;78:240-54

OcularPerfusionPressure&GlaucomaProgression–emergingparadigms

DX: POAG, ??? Is there a blood-flow problem here???

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OpticNerveHEADanatomy–bloodflowconsiderations

HayrehSS.Ischemicopticneuropathy.ProgRetEyeRes.2009;28:34–62

Structural evaluation - Diagnosis enhanced depth imaging [choroid] •  Choroidal thickness and perfusion/flow evaluation

•  Age, axial length, CCT, and diastolic ocular perfusion pressure are significantly associated with choroidal thickness in glaucoma suspects and glaucoma patients.

•  Degree of glaucoma damage was not consistently associated with choroidal thickness.

� Maul EA, Friedman DS, Chang DS, Boland MV, Ramulu PY, Jampel HD, Quigley HA. Choroidal thickness measured by spectral domain optical coherence tomography: factors affecting thickness in glaucoma patients. Ophthalmology. 2011 Aug;118(8):1571-9. 44

Hey! Maybe its choroidal blood flow after all Choroidal blood flow (arbitrary units)

Hey! Maybe its choroidal blood flow. After all that seems to be the case in AMD

ImplicationsofBFalterationswithÛÛIOP

Note: increased IOP induces • posterior rotation of the peripapillary sclera • flattening of the cup floor • thinning of the lamina cribrosa and the prepapillary neural tissue and • anterior movement of the central optic nerve relative to the LC

Which may be complementary to reduced blood flow OR a result of same

Sigal I, Ethier CR. Biomechanics of the optic nerve head. Exp Eye Res. 2009; 88,799-807 .

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Structuralevaluation–diagnosisenhanceddepthimaging

•  Laminacribrosaevaluation

•  Emerginginvestigations:CSFpressure(see:later)

ParkHY,JeonSH,ParkCK.Enhanceddepthimagingdetectslaminacribrosathicknessdifferencesinnormaltensionglaucomaandprimaryopen-angleglaucoma.Ophthalmology.2012Jan;119(1):10-20.ParkSC,DeMoraesCG,TengCC,TelloC,LiebmannJM,RitchR.Enhanceddepthimagingopticalcoherencetomographyofdeepopticnervecomplexstructuresinglaucoma.Ophthalmology.2012Jan;119(1):3-9. 49

Bloodsupplysummary•  Interindividualvariation*•  Retinalnervefiberlayer

–  CRA/CRV

•  Opticnervehead–  SPCaa–  choroidalplexus–  bloodsupplyissegmental

v  UltimatebloodsupplytoRNFLandONHisfromtheophthalmicartery,abranchoftheinternalcarotidartery

VascularTheoryofGlaucomaChangesinocularbloodflow(OBF)

•  Reducedperfusionpressure(beyondautoregulatorycapacity)leadingto...– Secondaryvasculardegenerationfollowingganglioncell/RNFLloss

VascularTheoryofGlaucomaChangesinocularbloodflow(OBF)

•  Peripheralvasculardysregulation-PVD– whichcanresultinreperfusioninjury(RI)

•  AllcanbeIOPindependentandmayinvolveboththeretinalandchoroidalcirculatorysystems.

Distribution of IOP in a general population*

N=nonglaucoma;G=glaucoma.*Dottedlinesrepresentareasofuncertainty.ShieldsMB.TextbookofGlaucoma.1998.

ImplyinganIOP-independentcomponentinglaucoma(“NTG”???)

WhatarethepossibilitiesintheabsenceofelevatedIOP?

•  Primary/Peripheralvasculardysregulation

•  InadequateONHperfusion

Let’stryandconnectthedots

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Relationshipofperfusiontoglaucoma

•  LowdiastolicocularperfusionpressuremaybeassociatedwithincreasedriskforPOAG.

•  Thisassociationwasconfirmedinsubjectstreatedforsystemichypertensioninsubgroupanalysis.Thismaysupportthehypothesisthattheconceptofocularperfusionpressurestatusmaybemorerelevanttoglaucomapathogenesisthanocularperfusionpressurealone.

Consultthepatient’sbeta-blockerprescriberinthecontextofprogressiveglaucomadamagewith“good”IOPcontrol.AmJOphthalmol2013;155:843–851.

PrimaryOBFcomponent•  Riskfactors(RF)for

atherosclerosisarelargelyparalleltoincreasedIOP–  age–  smoking–  dyslipidemia–  systemichypertension– malesex–  obesity

Flammer J, Mozaffariaeh M. What is the present pathogenetic concept of glaucomatous optic neuropathy? 2007. Surv Ohthalmol 52: S162-173.

PrimaryOBFcomponent•  Riskfactors(RF)for

atherosclerosisarelargelyparalleltoincreasedIOP–  age–  smoking–  dyslipidemia–  systemichypertension– malesex–  obesity

•  ThereforereducingtheseRFreducesIOP(slightly)–  physicalexercise– weightloss–  treatmentofdyslipidemia

•  AndmayincreasebloodflowandaqueousoutflowthroughtheTM

Flammer J, Mozaffariaeh M. What is the present pathogenetic concept of glaucomatous optic neuropathy? 2007. Surv Ohthalmol 52: S162-173.

•  GlaucomatousdiscandfieldchangeswithIOPconsistently<22

20%ofnewlydiagnosedglaucomapatientshaveIOP<21mmHgatpresentation

• CAUSE??Decreasedperfusionofdisc(arteriosclerosis,lowBP)

‘NormalTensionGlaucoma?’

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Recentevidence...

‘NormalTensionGlaucoma’

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Recentevidence...

‘NormalTensionGlaucoma’

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Perfusion

Pressure Blood Pressure

IOP

Lower Diastolic, Systolic, or

Mean Pressure Reduces Perfusion

Pressure

Higher IOP

Negatively Impacts Perfusion Pressure

Perfusion Pressure Is a Result of

A Delicate Balance Between IOP

and Blood Pressure

Lower Perfusion Pressure Is Associated with Increased Risk for

Open Angle Glaucoma Leske MC, et al. Ophthalmology  2007; 114,: 1965-72 Leske MC, et al. Ophthalmology 2008;115, 65-93.  Hayreh SS. Trans Am Acad Ophthalmol 1974;78:240-54

OcularPerfusionPressure&GlaucomaProgression POAG Risk Factors 9-year BES

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Leske MC, Wu SY, Hennis A, Honkanen R, Nemesure B; BESs Study Group. Risk factors for incident open-angle glaucoma: the Barbados Eye Studies. Ophthalmology. 2008 ; 115: 85-93.

mean perfusion pressure = 2/3(mean arterial pressure) - IOP Where mean arterial pressure = diastolic BP + 1/3 (systolic BP – diastolic BP)

PerfusiontotheONH•  DOPP(Diastolicocularperfusionpressure) =DBP–IOP

(Whatisthenumber?)

<40issignificant*-talktothePCP)

– ReducedinPOAG

Alternatively,meanperfusionpressure

*LeskeMC,WuSY,HennisA,HonkanenR,NemesureB;BESsStudyGroup.Riskfactorsforincidentopen-angleglaucoma:theBarbadosEyeStudies.Ophthalmology.2008;115:85-93.

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PerfusiontotheONH

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ExamplecomparingDOPPandmeanOPP120/80IOP=20;DOPP=60[80-20]WhatIOPdowemeasure?diastolic

Significantdifference Whichtouse???

MOPP=2/3[DBP=1/3(SBP-DBP)-IOP2/3[80+1/3(40)]–20resultsin42

2014(monkeys)

RecentassociationbetweenBP/OPPandstructuralglaucomaprogression

•  Twogreatestriskfactors– Olderage– LowerdiastolicBP

•  Structuralelementsassessed–ONH(rimtissue),RNFLthickness.

McGlynnMM,ErlichJR,MarlowED,etal.Associationofbloodandocularperfusionpressurewithstructuralglaucomatousprogressiionbyflickerchronoscopy.BrJOphthalmol2013.PublishedonlineSeptember24,2013

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EmergingimportanceofdiastolicBP

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•  LowmeandiastolicBPisconsistentlyassociatedwithstructuralglaucomaprogression(Rimtissue,RNFL)

McGlynnMM,ErlichJR,MarlowED,etal.Associationofbloodandocularperfusionpressurewithstructuralprogressioninglaucomaasmeasuredbyflickerchronoscopy.BrJOphthalmol.2013.

*Significantlylowerdiastolicperfusionpressurewasobservedinthosetakingoralhypotensivemedications(asinbeta-blockers)

2013,

CurrentOpinioninPharmacology2013,13:36–42www.sciencedirect

2013,

Modelofprimary&secondaryinsultsinglaucomaduetolowOPP

Influencesofabnormalautoregulationinglaucoma(proposedscheme)

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Contributingfactorstoabnormalneurovascularcouplinginglaucoma Conclusionsfromprevious

2014

So,whichismoreimportant,loweredBPorelevatedIOP?

Conclusions•  Theresultsshowthatopticnerveheadbloodflowismoresusceptibletoanocularperfusionpressuredecreaseinducedbyloweringthebloodpressurecomparedwiththatinducedbyincreasingtheintraocularpressure.

•  Thisbloodflowautoregulationcapacityvulnerabilitytolowbloodpressuremayprovideexperimentalevidencerelatedtothehemodynamicpathophysiologyinglaucoma.

2014

NOCTURNALHYPOPERFUSIONASAGLAUCOMARISKFACTOR

2014

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Conclusionsandguidance

•  Inconclusion,themagnitudeanddurationofnocturnalhypotensionidentifypatientswithNTGwhohaveVFprogression.

•  AmbulatorymonitoringofsystemicBPshouldbecomepartofroutineassessmentofpatientswithNTG,particularlyamongthosewhocontinuetoprogressdespiteIOPlowering.

Conclusionsandguidance

•  NocturnalBPshouldbeconsideredamodifiableriskfactorinNTG.

•  RandomizedtrialswillberequiredtoassesstheefficacyofdifferentinterventionsdesignedtoavoidnocturnalhypotensiontopreventVFlossinpatientswithNTG,aswellastotesttheeffectofmoreaggressiveIOP-loweringtherapyinthesecases.

ConclusionsandGuidance

•  BloodflowmeasurementscouldguidechangesintreatmentprotocolwithemphasisonnormalizationofcirculatoryalterationratherthanjustIOP.

*RecentassociationbetweennocturnalBPdipsandODHinNTG

KwonJ,LeeJ,ChoiJ,JeongD,KookMS.AssociationBetweenNocturnalBloodPressureDipsandOpticDiscHemorrhageinPatientsWithNormal-TensionGlaucoma.AmJOphthalmol.2017Apr;176:87-101.doi:10.1016/j.ajo.2017.01.002.Epub2017Jan12.

over-dippers=progressors

*RecentassociationbetweennocturnalBPdipsandODHinNTG

KwonJ,LeeJ,ChoiJ,JeongD,KookMS.AssociationBetweenNocturnalBloodPressureDipsandOpticDiscHemorrhageinPatientsWithNormal-TensionGlaucoma.AmJOphthalmol.2017Apr;176:87-101.doi:10.1016/j.ajo.2017.01.002.Epub2017Jan12.

è

over-dippers=progressors

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Reducedperfusion-MoreRiskfactors

•  Autoregulationdisturbances•  VasospasticDisorder•  Migraine•  Increasedresistance

• ✔Reducedbloodflow(20lowBP)→Nocturnalhypoperfusion

•  Sleepapneasyndrome85

SASandNormalTensionGlaucoma•  50sleepapneapatientswerecomparedwith40normals

•  PrevalenceofNTGamongSASptswas5.9%(and0%amongthecontrols)

•  SeverityofSASwascorrelatedpositivelywith[structuralandfunctionalelements]–  IOP–  MD–  C/D– meanNFLthickness(HRTII)

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Sergi M, Salerno DE, Rizzi M, et al.. Prevalence of Normal Tension Glaucoma in Obstructive Sleep Apnea

Syndrome Patients. J Glaucoma. 2007; 16: 42-46.

SAS–Glaucomaconnection(additionalevidence)

� Theprevalenceofglaucomainpatientswithobstructivesleepapneaisanestimated27%!

BendelRE,etal.Prevalenceofglaucomainpatientswithobstructivesleepapnoea-across-

sectionalcase-series.Eye.2007.

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OcularbloodflowandObstructiveSleepApneaSyndrome(OSAS)

•  31patientswithprovenOSAS/25controls

•  12.4%ofOSASandnoneofthecontrolswerediagnosedwithglaucoma

•  NodifferencesinretinalcirculationmeasuresorIOP(implyingIOP-independentrisks)

•  PositivecorrelationbetweenMDandLV&retinalcirculatorymeasures

Karakucuk S, et al. Ocular blood flow in patients with obstructive sleep apnea. Graefes Arch Clin Exp Ophthalmol. 2008; 246: 129-134.

SAS–Glaucomaconnection(furtherevidence)

� InpatientswithOSAS,ahighprevalenceofglaucomawasfound.

� VisualfielddefectsmaybeduetoopticnerveperfusiondefectsandthesefielddefectsalsoincreaseastheRI(resistanceindex)increases.

KarakucukS,etal.Ocularbloodflowinpatientswithobstructivesleepapneasyndrome(OSAS).GraefesArchClinExpOphthalmol.2008Jan;246:129-34.

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And,morerecentlyraisedquestions...

•  ShouldOSAHSbeincludedintheDDxofglaucoma?

•  IsOSAHSanotherglaucomaoracontributor?

•  DoesloweringIOPinOSAHSarresttheprogressionofopticneuropathy?

LinPW,FriedmanM,LinHC,ChangHW,PulverTM,ChinCH.Decreasedretinalnervefiberlayerthicknessinpatientswithobstructivesleepapnea/hypopneasyndrome.GraefesArchClinExpOphthalmol.2011Apr;249(4):585-93.Epub2010Oct19.

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Glaucoma - Glaucoma + Total Apnea - 64,825

(95.0%) 3,410 (5.0%) 68,236

Apnea + 2,497 (91.6%) 228

(8.4%) 2725

Total 67,322 3,638 70,960 Limitations and confounders * Boyle-WalkerM,SemesLP,ClayOJ,FuhrP,LiuL.SleepApneaSyndromeRepresentsaRiskforGlaucomainaVeterans’AffairsPopulation.ISRNOphthalmology.Volume2011,doi:10.5402/2011/920767.

“Fairandbalanced”

•  FoundthatthereISarelationshipbetweenIIHandAIONandthoseusingaC-PAPbutnotbetweenglaucomaandC-PAPuse.

SteinJD,etal.TheAssociationbetweenGlaucomatousandOtherCausesofOpticNeuropathyandSleepApnea.AmJOphthalmol.2011Aug17.[Epubaheadofprint]

2013,

And,theverylatest!

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And,theverylatest! Howshouldglaucomabemanagedcomprehensively?

•  First,lowerIOP

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Newdirectionsinglaucomatreatment

•  Yes,treatment•  BeyondIOPreduction,regulationofbloodflow...–  Systemically(regulatingbloodpressureandmonitoringperfusionpressure)

–  Locally–endothelial-cellactivitybymodulatingNitricOxide(NO)ThisistheNEXTBIGTHING!

•  Regulationofaqueousdynamicsatthetrabecularmeshworkbyvascularmodulation

•  Inaddition,theapplicationofNO-donatingcompoundsfortheloweringofIOPdirectly

AsofNov.2,2017...

Future options for medical management – targeting the site of glaucoma, the TM

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¨  latanoprostene bunod (a nitric oxide-donating compound, NO) Vyzulta (Valeant)

¨  FDA-approved November 2017

¨  MOAs: ¤  relax the cellular matrix of the TM (and perhaps more

distally) ¤ may also act at the endothelium of TM blood vessels to

constrict and therefore further open drainage pathways.

Future options for medical management – targeting the site of glaucoma, the TM

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¨  Rho-kinase inhibitors (Rhopressa and Roclatan, (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005%, Aerie) ¤  FDA-approved December 2017

¨  MOAs ¤  increase fluid outflow through the trabecular meshwork, (10

drainage) ¤  increase fluid outflow through the uveoscleral pathway, (20

drainage) ¤  reduce fluid production in the eye, and ¤  reduce episcleral venous pressure (EVP).

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How should glaucoma be managed comprehensively?

¨  Second, consider increasing perfusion (may be a consequence of lowered IOP) ¤  Topical treatments? (betaxolol, brimonidine, brinzolamide,

¤ Gingko Biloba and other CAM interventions ¤  Exercise, weight loss ¤  Lower cholesterol, blood sugar levels ¤  Treat underlying vascular disorders (HT, SAS, CVD) ¤  Etc.

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Anti-oxidant/Supplement formulation 110

HarrisA,GrossJ,MooreN,etal.Theeffectsofantioxidantsonocularbloodflowinpatientswithglaucoma.ActaOphthalmol.2017Aug3.doi:10.1111/aos.13530.[Epubaheadofprint]

Study design 111

¨  45 patients with confirmed glaucoma on IOP-lowering treatment (placebo controlled, X-over)

¨  Baseline and post-administration (@ 1 month) measurements ¤  IOP ¤ OPP ¤ Retrobulbar (ultrasound) and retinal capillary (Doppler)

blood flow

Results 112

¨  Increased peak systolic and/or end diastolic velocities among the active group (but not placebo)

¨  Reduced vascular resistance in central retinal and short posterior ciliary arteries

¨  Increased superior and inferior temporal retinal artery mean blood flow

¨  Enhanced retinal capillary density

SO, what were they given? 113

SO, what were they given? 114

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Howshouldglaucomabemanagedcomprehensively?

•  Third,reduceoxidativestress(Ca++blockade[BUT,notsystemicβ-blockers],supplements)ANDenhancebloodflow!

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NON-SELECTIVEBeta-blockers:Significantadditionalprecaution

Topicalβ-blockersadministeredatnighttothosetakingsystemicβ-blockersmayreduceperfusiontotheONHplusβ-blockertherapytoreduceIOPisineffectiveatnight.

Whichbringsusto...

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Hayreh SS. Effect of nocturnal blood pressure reduction on retrobulbar hemodynamics in glaucoma. Graefes Arch Clin Exp Ophthalmol. 2002; 240: 867-8.

2013, 2013,

Considerthis:

•  IsglaucomaAIONthathappensoveralifetime?• 

OR•  IsAIONglaucomathathappensovernight?

LiuC-H,etal.ComparisonoftheRetinalMicrovascularDensityBetweenOAGandnAION.IOVS.2017;58:3350–3356.DOI:10.1167/iovs.17-22021

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62WM

•  Complainedofvisionlosssuperiorlyinthelefteye(May,2018)

•  VA20/20OD,OS;(L)RAPD2+;IOP11,9mmHg.•  Seenbyprimary-careOD– Dx=NTG,initiatedonlatanoprostqhs.

_____________________________________•  Sentforconsultation/SLTduetosignificantVFdepressions.(June2018)

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CONTINUOUSIOPMEASUREMENT

Theholygrailofglaucomawhetheritisdiagnosisormanagementis...

Closingthoughts

• How can IOP (and BP) be monitored continuously?

• What impact may this have on management?

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Stateswithonlyfourletters

•  Iowa•  Utah•  Mississippi•  Tennessee•  Alaska•  Hawaii•  Indiana•  Kansas

Thank You

leopsemes@gmail.com