Post on 31-May-2022
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SleepDisorders:WhatOptometrists
NeedtoKnowA.PaulChous,MA,OD,FAAO
Tacoma,WA
Disclosures• Ihavespokenfor,beenonadvisoryboardsfororhavebeenpaidconsultantsfor:
Bausch&Lomb,Genentech,Konan,NovoNordisk,Optos,Optovue,Regeneron,VSP,Zeiss,ZeaVision
MyFocus• Sleepproblemsareprevalent
• Sleepproblemscontributetoeyedisease&systemicdiseasethatislinkedtoeyedisease
• ECPscanhelppatientswithsleepproblemsgetdiagnosedandtreated
SleepDisorders–WhatWeThinkOf
It’sNOTJustSleepApnea• BroaderDefinitionofSleepDisorders
– Parasomnia:episodicsleepeventsincludingsleepterrordisorder,sleepwalkingandnightmaredisorder
– -Dyssomnia:abnormalitiesintheamount,duration,qualityortimingofsleep;PrimaryvsSecondary
=MostPrevalent
Sleep Walking Talking
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Dyssomnia• Primary:Primaryinsomnia,narcolepsy,circadianrhythmdisorders,andsleepdisorderedbreathingincludingsleepapnea(central,obstructive,mixedforms)
• Secondary:sleepdisorderscausedbypsychosocialstressors,anxiety,depression,diet(caffeine/alcohol/nicotine),medications(anti-depressants)
Epidemiology• Estimatedthat20-40%ofAmericansexperiencesleep
problemseachyear• 50%ofthose>50yearsold
• 25%offatalmotorvehicleaccidentsareduetosleepinessordriverfatigue
• Sleepdeprivationsignificantlyincreasesriskofmedicalerrors– 100Kdeathsin2006;250,000in2016– CommitteeonSleepMedicine,WashingtonD.C.,TheNationalAcademiesPress2006– SleepReview,February27,2017
MMWRMorbMortalWklyRep.2014;63:557-562.
• 17-18.5hoursofwakefulnessimpairsmotorfunctiononaparwithormorethanabloodalcoholcontent(BAC)=0.05%
• 17.74-19.65hourswithoutsleepwasequivalenttoBAC=0.10%
SleepDurationAcrosstheLifespanSleepMedRev.2012Jun;16(3):199–201.
Insomnia• Prolongedsleeplatencyand/orreduceddurationofsleep– Acute:30%ofAmericanseachyear(>1monthduration)– ChronicInsomniaSyndrome:10%eachyear(>3monthsduration)
– Ifadjustedfordepression,about6%/year– Bydefinition,accompaniedbyinterferencewithwakefulactivity(e.g.excessivedaytimesleepiness=EDS)
JClinSleepMed.2007Aug15;3(5Suppl):S7–S10.
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Hyposomnia:ShortSleep(<7h)isCommon
• BehavioralRiskFactorSurveillanceSystem2014• 35%ofUSadults
– 68%ofteensget<8hours(NSFrecommends8.5)
• 46%ofAfricanAmericans&NativeHawaiians• SignificantlymorecommoninadultswithCAD,stroke,asthma,COPD,diabetes,CKD,depression
PrevalenceofShortSleepDurationbyState,2014CDCBRFSSData AverageSleepDurationinUSAdults
2hourreductionsince1960
Doyougetenoughsleepandisitimportant?
FewerpeoplereportingEnoughsleepovertime
Maximalwell-beingscoresAt8hourspernight
MyPatients• 50yopsychiatristwithT2DMandBMI=40Kg/m2
– GlaucomaSuspectinforthresholdvisualfield– Fallsasleep/snoring3Xduringperimetry
• 40yointernistjustoffof48hourhospitalshiftinforroutineeyeexam– “Howareyoudoing?”– Sobbingb/chescreamedathisfavoritenurse
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SleepApnea• Cessationofbreathduringsleep• About20%ofUSadults• Roughly15%ofthesearesymptomatic
30-50%RestrictionofFlow80-100%RestrictionofFlow
SleepApnea• MostcaseareObstructive(OSAS)
– 22%ofmen/17%ofwomen!22millionAmericans
– Ratesincreasewithage&obesity!80%unDx• <10%arecentral-<1%ofpopulation
– Decreasedorabsentventilatoryeffort(neurologic)• Apnea:temporarycessationofbreathing(>10seconds)
duringsleepwithreducedO2saturation• Hypopnea:decreasedairflow>10secwithreducedO2
saturation(partialobstruction)– ElevatedApnea-HypopneaIndex(AHI)
JThoracDis.2015Aug;7(8):1311–1322
AHIapneic+hypopneicepisodes
timeasleep(inhours)
• AHI<5=normal• AHI>5<15=mildapnea• AHI>15<30=moderateapnea• AHI>30events/hour=severeapnea
• 15%ofallOSAismoderateorworsebyAHI• MilderOSAfarmorelikelytobepositional
EurRespJ2016;47:23-26 Chest2005Oct;128(4):2130-7
OtherSleepDisorders• RestlessLegSyndrome:legdiscomfortcoupledwithcompulsivemovement;Symptomsworsewhenstationary;females>males;5.5%ofthepopulation
• Narcolepsy:excessivedaytimesleepiness,sleepparalysis,hallucinations,+/-cataplexy;males<females;79.4casesper100,000
Sleep2018;41(suppl1):A227
SleepMed2011;12(7):623-34
.Neurotherapeutics.2012;9(4):776–790
• Oftenworsenedbyantihistamines,melatonin,alcohol,SSRIs
• RLSincreasestheriskofsuicideandself-harmbyupto4-foldafteralladjustments– 24+KRLSpatientsfollowedover8years
JAMANetwOpen.2019;2(8):e199966.Epub2019Aug2
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ToolsforAssessingSleepSymptoms• EpworthSleepinessScale(ESS)
– Questionsaboutsleepinessduringwakeactivity
• PittsburghSleepQualityInventory(PSQI)– Questionsaboutsleeplatency,quality,breathing
• LittlecorrelationbetweenESS&PSQI• Bothpoorpredictorsofmilderobstructivesleepapnea(OSA)
&othersleepdisorders
• BerlinObstructiveSleepApneaSurvey• STOP-BANGApneaQuestionnaire(snore/tired/observed/
pressure–BMI/age/neckcircumference/gender)
SleepMed.2014Apr;15(4):422-9.
IntJPrevMed.2018Mar9;9:28
Polysomnography(PSG)
• Goldstandardfordiagnosisofmostsleepdisorders(exceptRestlessLegSyndrome)
• Overnightmeasurementofbreathing,pulse,P02,EEG,REM,legmovements
• Homesleepstudiesrecordpulse,P02,breathing– GoodcorrelationwithPSGforDxofOSA– Costsaretypically$200-500versus$1500-2000
Respirology.2010Feb;15(2):336-42
ESAP:EasySleepApneaPredictor• 100%specificityformildOSASinT2DM(n=43)when
comparedwithPSG• Neckcircumference>17/16inchesinmales/femalesalso
100%specific• BothmorespecificbutlesssensitivethanBMI>35and+
STOP-BANG• ApositiveESAPwasdefinedasa1cmgapwhenapatient
encircledtheirhandsaroundtheneck
SleepDisord.2019;2019:3184382.
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SleepDisordersAssociatedwithRiskofMultipleSystemicPathologies
• CardiovascularDisease• Diabetes/InsulinResistance/Obesity• IntestinalDysbiosis• Hypertension
• Sub-optimalresponsetotreatmentoftheabove
https://www.cdc.gov/sleep/about_sleep/chronic_disease.html
CVD• ObstructivesleepapneaincreasestheriskofstrokeandMImorehan3-fold,butCPAPdoesn’tlowerriskofrecurrenteventspermultipleanalyses*
• Meta-analysisshowssleepapneadoublestheriskofMACEafterstentplacement
• UntreatedOSASincreassriskofheartfailureby140%viahypoxicdamagetocardiacmuscle
• 10-yearanalysisshowsInsomniaincreasesriskofMIandstrokeby13%
Medicine(Baltimore).2018Apr;97(17):e0621
EurJClinInvest.2018May;48(5):e12908.
*MOREonthisLATER
TexHeartInstJ.2018Jun;45(3):151–161
Neurology2019Dec3;93(23):e2110-e2120
Diabetes• Shortsleep(<5.5hours)triplesthelikelihoodofT2DM
inobservationalstudiesafterallcontrols
• Severeobstructivesleepapneaincreasedincidentdiabetes71%over13yearsindependentlyofadiposity
• Bothshort(<5.5hrs)andlong(>9hrs)sleepdurationaresignificantlyassociatedwithadiposity&insulinresistance
CurrDiabRep.2018Aug17;18(10):82.
SleepMed.2016Sep;25:156-161
DiabetesResClinPract.2018May;139:195-202
DiabetesCare2015Mar;38(3):529-537480K+subjects
“SweetSpot”is7.7hours
ShortSleepèêLeptin(adipocytes)&éGhrelin(stomach)èéappetite/BMI
PLoSMed.2004Dec;1(3):e62 HTNandOSA• 50%ofhypertensivepatientshaveOSA• Drug-resistantHTNishighlywassociatedsevereOSA
Hypertension.2014Feb;63(2):203–209.
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OSA+HighFatDiet!Dysbiosis,HTN• Ratswithtrachealballoon-inducedapneaandhigh-fatdietdevelopsignificantdecreaseinbutyrate-producingbacterialfloraand29mmHgBPincreaseafter2weeks
• Fecaltransplantationintonormalratsresultedina32mmHgincreaseinBPat2weeks
• SuggestsacausalnexusforHTNbetweensleepapnea,dysbiosisandfatintake Hypertension.2016Feb;67(2):469–474.
ReductionsinbutyrateproducingbacteriaareprevalentinT2DM&HTN MedSci(Basel).2018Jun;6(2):32
Microbiome.2017;5:14.
GutMicrobiomeAffectsSleep• Antibioticstotallyinactivatetryptophan-serontoninsignallinginmice
• Highertryptophanbutlittleserotonin• SignificantlymoreREMtonon-REMsleeptransitions
• Improvingguthealth&diversity("saturatedfatand#fermentedfoods,probiotics)mayimprovesleep
Gutmicrobiotadepletionbychronicantibiotictreatmentaltersthesleep/wakearchitectureandsleepEEGpowerspectrainmice.ScientificReports,2020
PLoSOne.2019;14(10):e0222394.
SleepDisordersAssociatedwithMultiple,PrevalentEyeDiseases
• OSA:normotensiveglaucoma,NAION,DR&DME,Poorresponsetoanti-VEGFTxinnvAMD&DME,FloppyEyelidSyndrome
• Insomnia:AMD• Hyposomnia:nvAMD,POAG,dryeye,myopia• Hypersomnia(excessivesleepduration):Sight-threateningDR,AMDwithgeographicatrophy,POAG
ApneainDiabeticRetinopathy/DME• STDRrateswere2-2.5XhigherinT2DMpatients(n=230)with
untreated/under-treatedOSAfollowedfor4yrs• Afteralladjustments,OSAincreasedoddsofprogressingto
severeNPDR/PDR5-fold• AHI>11.9vs<4.8increasedoddsofSTDR7.5-fold• CSMEpatientswithconfirmedOSA&Txwithgridlasergainedan
extralineofVAiftreatedwithCPAP>2.5hrs/night@6months
• DMEpatients(n=30receivingAvastin),theprobabilityofOSAsymptomswasdirectlyproportionaltothe#ofrequiredinjections
AmJRespirCritCareMed.2017Oct1;196(7):892-900.
Retina.2014Dec;34(12):2423-30
Respiration.2012;84(4):275-82
DR&Hypersomnia• 1231T2DMpatientsinSingapore• Longsleepduration(>8hrs)&EDSwereindependentlyassociatedwithVTDR(3-fold)
• Hypothesis:RetinalO2demandispredominantlydrivenbyrodmetabolism;increasedsleepmaybeahypoxicstimulustoworseningretinaldisease
PLoSOne.2018;13(5):e0196399
VTDRisProliferativeRetinopathy(PDR)orcenter-involvedmacularedema(CI-DME)
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A novel approach to DR n InnerretinalhypoxiaisprimarilyresponsibleforDRandvisionloss
n RodsareprimarilyresponsibleformostretinalO2consumptionduringdark
n LimitingrodmetabolismwithagreenLEDreduceshypoxicstressinanimalsandimprovedDMEin17/26eyesversus3/26controleyes
Diabetic retinopathy and a novel treatment based on the biophysics of rod photoreceptors and dark adaptation. Editors In: Kolb H, Fernandez E, Nelson R, editors.
GeographicAtrophy• Afteralladjustments,longsleep(>8hours)increasedtheriskofGA7.1timescomparedtopatientswithoutAMD– 1003consecutiveptsinaSanFranciscoretinapracticesurveyedaboutsleephistory
– HourssleepingwasnotassociatedwithnvAMD
Retina.2016Feb;36(2):255-8.
?nvAMD• InacaseontrolstudyofAMDptswithself-reportedshortsleep
(<6hours),relativeriskofCNVMwas3.29v.7-8hrs;2.25for6-7hrs;1.39for>8hrs(n=165)– HR=3.1forshortsleepafterallcontrols(p<0.01)
In38patientswithnvAMDandOSAconfirmedbyPSG,CPAP+AvastinimprovedVA(20/40vs20/100),CSTby-78μandcutrequiredAVTinhalfcomparedtoAvastinalone(8vs16injections)
Retina.2016Apr;36(4):791-7.
OphthalmicEpidemiol.2016;23(1):20-6.
PoorResponsetoAVTinUntreatedOSA
Glaucoma• POAGwasassociatedwithshort(<5hrs)andlong(>9hrs)sleepduration(p=0.07)
• Whenstratifiedbyabdominalobesity&BMI,overweightsubjectswere2.4XmorelikelytohavePOAGifsleepdurationwas>9hrsor<7hrsafteradjustmentsforage/gender/IOP/HTN/smoking/drinking/income/depression(p=0.036)– 9400subjectsfromKNHANES2012
Medicine(Baltimore).2016Dec;95(52):e5704.
‘SweetSpot’’
SleepdurationsignificantlyassociatedwithPOAGinabdominallyobesesubjects
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NormotensiveGlaucoma
• NTGappearstobemoreprevalentinOSAandviceversa
• PresenceoffloppyeyelidsyndromeinptswithOSAassociatedwitha4-fold+increaseinglaucoma(NTG&POAG)– 23%vs5%p=0.04– 150FESpatients
JGlaucoma.2014Jan;23(1):e81-5.
JGlaucoma.2007Jan;16(1):42-6BMCOphthalmol.2014Mar10;14:27
MySimpletonConclusion• Sickretinasandopticnervesneedtobreathe
• Sickretinasandopticnervesneedadequatesleep,butnottoomuchortoolittlesleep
DryEye• Shortandveryshortsleepdurationincreasedoddsofdryeyesymptoms– HR=1.2(5hrs)and1.29(<4hrs)– 16KfomKNHANES
• ClinicalandsubjectivedryeyesignificantlymorecommoninpatientswithpoorPSQIscores– Osakastudyn=672Japaneseofficeworkers– 730ptsatTokyoeyeclinic
SleepMed.2015Nov;16(11):1327-133
ClinOphthalmol.2016;10:1015–1021.NeuropsychiatrDisTreat.2015;11:889–894
Mechanisms?• Experimentalsleepdeprivation(mice)induceslacrimalglandhypertrophyandreducestearproductionafter10days– Reversedafter14daysofrest
• Sleepapneasignificantlyassociatedwithpersistent/severedryeyesymptomsinastudyof120USVeterans(3.8X)– CPAPusenotreported
ExpMolMed.2018Mar2;50(3):e451
JAMAOphthalmol.2016Dec22.
SleepDeprivationDryEye(SDE)• SDEresultsfromchangesinmorphologyofcornealepithelialmicrovilliandêtearstabilityresultingfrominhibitionoftheproteinPPAR-α (mousemodel)
• Topicalfenofibrate(anti-lipidagentTricor™)activatesPPAR-α andnormalizesmicrovilli&tearfilmstability
InvestOphthalmolVisSci.2018Nov1;59(13):5494-5508
CPAPuse&OSD• Conjunctivalsquamousmetaplasiaincreased&TBUTdecreasedinrighteyesonlyafter4monthsofCPAP(n=80)– Positionaleffect?(maskvshabitualsleepposition);maskleakage,maskdisplacement,nasolacrimalairflow
Cornea.2012Jun;31(6):604-8
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EyeEco’sEyeseals4.0.
SleepReview2016InterviewofArtEpstein,OD,FAAO
DoesCPAPIncreaseIOP?• NodifferenceinmeanIOPatbaselineandafter7hoursin31subjectswOSA+/-CPAP
• NocturnalIOPwassignificantlyhigherin21CPAPsubjectsmeasuredQ2h– Meantrough/peakspreadincreasedfrom6.7to9.0mmHgafter1month
– DecreasedIOPwasseenafter30minutesCPAPcessation
GraefesArchClinExpOphthalmol.2015Dec;253(12):2263-71
InvestOphthalmolVisSci.2008Mar;49(3):934-40.
Hyposomnia&Myopia• 3625Koreanadolescents(12-19yo)• Myopiawasinverselyassociatedwithsleepdurationaftercontrols(0.1D/hour)
• Comparedtosubjectsgetting<5hrs,ORformyopia>-0.50D<6.00Dinthosegetting>9hrswas0.59(p=0.006)
• Norelationshipwasseenformyopia>6diopters
ActaOphthalmol.2016May;94(3):e204-10.
HowDoWe‘Fix’PoorSleep?
CombattingPoorSleep• Removelocalfactors(quiet/darkroom;avoidcaffeine/
nicotine/alcohol&lightatnight)– Bluelightsuppressesmelatonin,impairssleeplatency,durationofREM–559studiesin5yrs
• Identify&treatpsycho-socialstressors(anxiety/depression)• Avoidnapping,shiftworkandvariablebed/wakingtimes
• Physicalactivity• Identify&treatOSA
NationalSleepFoundation
$DrugTherapyinsomnia!Sonata,Lunesta
nightterrors!clonazepam,prazosinRLS!carbidopa,gabapentin,Fe
AvoidLight-at-Night• LANdisruptsthecircadianrhythmandmetabolism,increasingratesofobesityandmetabolicdisorders
• Indoorandoutdoornightimelightingaffectssleepqualityandquantity
EndocrRev.2014Aug;35(4):648-70.
Sleep.2016Jun1;39(6):1311–1320
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SchoolStartTimes• TheAmericanSocietyofPediatricsrecommendsthatmiddleandhighschoolsstartnoearlierthan8:30AM
• Veryfewschoolsdoso
TreatingOSA• CPAPisthegoldstandard,butcomplianceratesarelow(50%discontinuewithinthefirstyearandanother25%byyear3)
• Females,>55yoandimproveddaytimesleepiness(ESS)predictcompliancepast6mos
• CPAPdidNOTimproveMACEormortalityinptswithestablishedCVD(meannightlyuseonly3.3hrson70%ofnights)
RespirCare.2010Sep;55(9):1230-9
SleepApnea.NEnglJMed.2016Sep8;375(10):919-31
SAVETrial(n=2717)SleepApneacardioVascularEventstrial
Meannightlyusewasonly3.3hrson70%ofnights!
PtswithsevereO2desaturationAnddaytimesleepinesswereexcluded
Allsubjectshadestablishedcoronaryarteryand/orcerebrovasculardisease
DoseMayBeCriticalforCPAP• TheSAVEStudydidshowa44%reductioninstrokeriskforthosewith‘goodcompliance’– >4hrson70%ofnights
• CPAPuse>4hours/nightdoessignificantlyreduceMACEinmeta-analysis– 4RCTs,3780patientsp=0.02
AmJCardiol.2017Aug15;120(4):693-699
OtherOSATxOptions• MandibularAdvancementDevices(MAD)
– comparabletoCPAPformildOSA(50-60%lowerAHI)
• Uvulopalatopharyngoplasty(UPPP)– removaloftonsils,posteriorsoftpalate,uvula
• TargetedHypoglossalNeurostimulation– improvestonguemuscletonus
• Playingadouble-reedinstrument(e.g.anoboe)– lowerprevalenceofOSA
• Playdidgeridoo-comparabletoCPAPformild-moderateOSA
• WeightLoss
DtschArzteblInt.2018Mar;115(12):200–207MayoClinProc.2009Sep;84(9):795–800.Sleep.2015Oct1;38(10):1593–1598JClinSleepMed.2012Jun15;8(3):251–255BMJ.2006Feb4;332(7536):266–270
UPPP
THN OboeDidgeridoo
MAD
TongueBaseRadiofrequency GenioglossusAdvancement
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Excess Body Weight
Sleep Disorders NatSciSleep.2013;5:27–35
WeightLossImprovesDysomnia• Overweight/ObeseT2DMpatients(meanBMI=36.7)andOSAwholost30lbsover1yearreducedtheirmeanAHIfrom23.2to13.5
• ImprovedOSAscorespersistedafter4yrs(meanchangeAHI=-7.7)despite(mean=15lbs)weightgain
• Decreasedvisceralfat(600Kcaldeficit+/-exercise)significantlyimprovedsleepsymptoms(insomnia,EDS,apnea)inoverweight/obese
ArchInternMed.2009Sep28;169(17):1619–1626.Sleep.2013May1;36(5):641-649A
BehavSleepMed.2016May-Jun;14(3):343–350.
Conclusions• Sleepdisordersareprevalentandcontributetovisionlossandmortality
• ECPsshouldaskpts/partnersaboutsleepquality/quantity(STOP-BANG)
• ECPsshouldinitiatereferralforDxofhigh-riskpatients
• ECPsshouldassess/treatocularsequelaeofsleepdisordersaswellaspossibleCPAP-relatedocularadverseevents
• ECPsshouldeducateonsleephygiene&therapies
Summary
ThankYou!
PaulChous
dr_chous@diabeticeyes.com