Uveitis:apracticalapproachBruceR.Saran,MDChesterCountyEyeCareAssociatesVantageEyeCareWestChester,Exton,Jennersville,PAAdjunctAssistantClinicalProfessorofMedicineScheieEyeInstitute,UniversityofPennsylvaniaSchoolofMedicinePhiladelphia,PA
“uveitiscommunication”
ClassificationofUveitis
§ basedonanatomy:theportionoftheuveainvolved
§ clinicalcourse:acute,chronic,orrecurrent
§ etiology:infectiousornon-infectious
§ clinicalhistology:granulomatousornongranulomatous
-allintendedtoaidindiagnosisandtreatment
TheStandardizationofUveitisNomenclature(SUN)WorkingGroup
Broadetiologiccategories:§ infectious § non-infectious
Anatomicalclassificationinto4groups§ AnteriorUveitis§ IntermediateUveitis§ PosteriorUveitis§ Panuveitis
TheSUNWorkingGroupAnatomicalClassificationofUveitis
TypePrimarySiteofInflammation Includes
ì AnterioruveitisAnteriorchamberIritis
Iridocyclitis
Anteriorcyclitis
ì IntermediateuveitisVitreousParsplanitis
Posteriorcyclitis
Hyalitis
ì PosterioruveitisRetinaorchoroid Focal,multifocal,ordiffuse Choroiditis,Chorioretinitis,Retinochoroiditis, Retinitis,Neuroretinitis
ì PanuveitisAnteriorchamber,vitreous,andretina/choroidinvolved
TemporalDescriptorsinUveitis
Onset:Sudden Insidious
Duration:Limited <3months'duration
Persistent >3months'duration
CourseAcute suddenonsetlimitedduration
Recurrent Repeatedepisodesseparatedby periodsofinactivitywithouttreatment >3months‘duration
Chronic Persistentuveitiswithrelapse<3monthsafter discontinuingtreatment
AnteriorUveitis:sub-classes“painfulredeye”
Theanteriorchamberistheprimarysiteofinflammation:
§ iritis: confinedtotheanteriorchamber
§ iridocyclitis: spillsoverintotheretrolentalspace
§ keratouveitis: involvesthecornea
§ sclerouveitis: involvesthesclera&uvea
IntermediateUveitis
majorsiteofinflammationisthevitreous
§ Inflammationofthemiddleportion(posteriorciliarybody,parsplana)oftheeye
§ manifestsprimarilyasfloaters-affectingvision
§ externallyappearsquiet
§ visuallossusuallyfromcystoidmacularedema(CME)orcataract
PosteriorUveitis
ì intraocularinflammationprimarilyinvolvingtheretinaand/orchoroid.
ì Inflammatorycellsmaybeobserveddiffuselythroughoutthevitreouscavity,overlyingfociofactiveinflammation,orontheposteriorvitreousface.
Ocularexaminationreveals
ì focal,multifocal,ordiffuseareasofretinitisorchoroiditis,with
ì varyingdegreesofvitreouscellularactivity
Panuveitis
ì primarysitesofinflammationinpanuveitis(diffuseuveitis)aretheanteriorchamber,vitreous,andretinaorchoroid.
ì associatedwithmanysystemicinfectiousandnon-infectiousdiseases
History:directedatthese“stem”etiologies§ Infectious§ Genetic§ Autoimmune§ Systemic§ Neoplastic§ Post-traumatic§ Idiopathic
“clinicalgestalt”
History:basicsimportant
Recreational/Occupationalactivities§ swimming:leptospirosisand
trematodegranulomas§ dogorcatowners:Toxoplasma&
Bartonella,Toxocaracanii§ Hikers/hunters:Lyme,WestNile§ Plumbersandsewerworkers:
leptospirosis§ Cattle/slaughterhouse:
Leptospirosis,cysticercosis§ Pigs/slaughterhouse:Cysticercosis,
Leptospirosis§ Prostitute/IVDrug:syphilis,TB
§ Age§ Children:JRA,Toxoplasmosis§ Youngadults:HLAB-27,MS,Behcet's§ Older:post-cataract,Zoster
§ Gender§ Males:Ankylosingspondylitis,Reiters,Behcet's,§ Females:Rheumatoidarthritis,JRA,collagenvascular
§ Race§ Caucausian:Ankylosingspondylitis,Reiters§ AfricanAmerican/Scandinavian:Sarcoid§ Asian:VKHsyndrome§ Greek/Turkish:Behcet's
SystemicSymptoms§ Pulmonary
Cough,shortnessofbreath-Tuberculosis,sarcoidosis,Pneumocystiscarinii,malignancy,WegenergranulomatosisNodules,hilaradenopathy,infiltrates-sarcoidosis(hilaradenopathy),malignancy,tuberculosis,Pcariniipneumonia
§ GastrointestinalDiarrhea-Crohn’s,ulcerativecolitis,WhippleDiseaseJaundice/hepatosplenomegaly-Brucellosis,CMV,sarcoidosis,infectioushepatitis,autoimmunehepatitis
§ Head/CNS§ Headaches-VKH,Sarcoidosis,Behçet,TB,Zoster,
Cryptococcus,toxoplasmosis,Lyme§ Auditory/vestibular-VKHdisease,Sarcoid,Wegener’s,Eales,
Syphilis§ Cranialneuropathy-Lyme,Sarcoid,MS,Syphilis,Herpes
simplex§ Psychosis-VKHdisease,Behçet,Lupus§ Cerebralvasculitis-Acuteposteriormultifocalplacoid
pigmentepitheliopathy(APMPPE),Behçet,Herpessimplex,herpesZoster,Syphilis,Lyme
§ Ear/Nose/Throat§ Bilateralearpinnainflammation-Relapsingpolychondritis§ Saddlenosedeformity–Wegener’s,Syphilis,relapsing
polychondritis§ Oralulcers-Behçet,SLE,herpessimplex,Reiter
syndrome,UlcerativeColitis§ Sinusisitis-Sarcoid,Wegenergranulomatosis§ Salivary/lacrimalglandswelling-Sarcoid,lymphoma§ Lymphadenopathy-Lymphoma,HIV,toxoplasmosis
SystemicSymptoms§ Musculoskeletal
Arthralgias/arthritis-Behçetdisease,sarcoidosis,SLE,juvenileidiopathicarthritis(JIA),Lymedisease,syphilis,psoriaticarthritis,Reitersyndrome,ulcerativecolitisSacroiliitis-Ankylosingspondylitis,Reitersyndrome,inflammatoryboweldisease
§ ConstitutionalFever-Reitersyndrome,Behçetdisease,PAN,inflammatoryboweldisease,HIV,tuberculosis,coccidioidomycosis,Whippledisease
Nightsweats-Malignancy,tuberculosis,sarcoidosis,coccidioidomycosisFlulikesymptoms-APMPPE,multipleevanescentwhitedotsyndrome(MEWDS),autoimmunehepatitis
§ Genitourinary§ Genitalulcers-Behçet,Reitersyndrome,syphilis§ Hematuria-Wegenergranulomatosis,PAN,SLE§ Circinatebalanitis-Ankylosingbalinitis,Reitersyndrome§ Urethraldischarge-Reitersyndrome,syphilis§ Nephritis-PAN,Wegenergranulomatosis,tubulointerstitial
nephritisanduveitis(TINU)§ Epididymitis-PAN,Behçetdisease,Reitersyndrome
§ Dermatologic§ Alopecia-VKHdisease,syphilis§ Vitiligo,poliosis-VKHdisease§ Nodules-Sarcoidosis,Lupus,Crohn’s,ulcerativecolitis§ Rash-Syphilis,Lymedisease,Reitersyndrome,leprosy,sarcoidosis,
herpeszoster,Behçetdisease,psoriasis,SLE,Kawasaki§ Keratodermablennorrhagicum-Reitersyndrome,ankylosing
spondylitis§ Erythemanodosum–Behçet’s,sarcoidosis,APMPPE
Ocularsymptoms:acuteanterior
ì Pain,photophobia,rednessandblurredvision
-inflammationoftheirisor,morerarelyfromsecondaryglaucoma.
-referredpaintolargerareaservedbycranialnerveV(theTrigeminalNerve)
ì Epiphora-reflextearingfrompain
ì Photophobia-lightexacerbatespainwithirismovement
Ocularsymptoms:chronicanteriormainsymptomisgraduallossofvision
§ calcificbandkeratopathy
§ Cataract
§ CME
pain&photophobiaareusuallyNOTpresent
Ocularsymptoms:Intermediateuveitis
q Floaters:vitreouscellsandsnowballsandrarelyvitreoushemorrhage
q Blurredvision:CMEorvitreousopacitiesinthevisualaxis
Ocularsymptoms:Posterioruveitis
§ painless
§ decreasedvisualacuity:CME,pucker,edema,ischemia
§ floaters:vitreousveils,vitreoushaze
§ photopsia:vitreousfloaters
§ metamorphopsia:CME,pucker,choroidalneovascularization
§ scotomata:retinalorchoroidaldysfunction
Ocularsymptoms:Episcleritisvs.Scleritis
Episcleritis§ Younger
§ mildpain,peaksin12hoursandthenslowlyresolvesoveraweek
§ blancheswith2.5%Neosynephrine
§ OralNSAIDs
Scleritis§ Anteriorscleritis(mostcommon)or
posterior
§ Anterior-subdivided1)diffuse2)nodular3)necrotizing
§ Older50-60s+
§ connectivetissuedisease,Rheumatoidarthritis,
§ NoHLAassociation
ìScleritisclassificationafter10%neosynephrine
3+
4+
Theexam
TheStandardizationofUveitisNomenclature(SUN)WorkingGroup
Irisinanterioruveitis
• anteriororposteriorsynechiae,
• irisnodules:• Koeppenodulespupillaryborder|A• Busaccanodulesirisstroma|B• Berlinintheangle|C
• heterochromia:Fuchs
• stromalatrophy:herpetic
• Dilation-therapeuticanddiagnostic
Intraocularpressure(lOP)
q low(mostofteninacute/recurrent)secondarytodecreasedaqueousproductionorincreasedalternativeoutflow
q elevation-ifthemeshworkbecomescloggedbyinflammatorycellsordebrisortrabeculitis
q Pupillaryblockwithirisbombeandsecondaryangleclosure–cancauseacuteriseinlOP
NationalEyeInstituteforvitreousgrading
Vitreousandposteriochamberexam
§ Vitreousinflammatorycells&vitreoushaze
§ snowballopacities:commoninintermediateuveitis&sarcoidosis
§ Snowbank:inferiorwithfluffyorshaggyappearance
§ vitreousstrands
§ cycliticmembraneoverciliarybodycanleadtociliarybodyandretinadetachment(hypotony)
PosteriorSegment
ì Retinalandchoroidalsignsmaybeunifocal,multifocal,ordiffuse
ì retinalorchoroidalinflammatoryinfiltrates
ì inflammatorysheathingofarteriesorveins
ì exudative,tractional,orrhegmatogenousretinaldetachment
ì retinalpigmentepithelialhypertrophyoratrophy'
ì atrophyorswellingoftheretina,choroid,oropticnervehead‘
ì preretinalorsubretinalfibrosis
ì retinalorchoroidalneovascularization
OfficebasedDiagnosticTesting
ì OCT:helpsdefineandquantifymacula,retinachoroidpathology
ì B-modeultrasound:diagnosticinposteriordisease
ì Angiography:diagnosticandoftenprognosticinposteriordisease
Targeted Epidemiology
ì InU.S.,80%ofuveitisisnon-infectious
ì Anterior>panuveitis>posterior>intermediate
ì 50%ofpatientshaveanassociatedsystemicdisease
ì Accountsfor10-15%ofallcasesofblindnessintheUS
“clinicalgestalt”
LaboratoryandMedicalEvaluation
noonestandardizedbatteryofteststhatneedstobeorderedforallpatientswithuveitis:guidedbyhistoryandexam
ì Purifiedproteinderivative(PPD)skintestorQuantiferonGold
ì Serumangiotensin-convertingenzyme(ACE)
ì Syphilisserologies
ì HLA-B27
ì ChestX-rayorCT
ì InChesterCounty:Lymeserology
Scleritismedicalworkup
§ completephysicalexamination
§ renalfunction
§ completebloodcount(CBC)withdifferential
§ erythrocyesedimentationrate(ESR)
§ C-reactiveprotein(CRP)
§ urinalysis
§ syphilisserology
§ sarcoidosisscreen.
serumautoantibodyscreenincluding:
§ antinuclearantibodies
§ anti-DNAantibodies
§ rheumatoidfactor
§ antineutrophilcytoplasmicantibodies
MedicalManagementofUveitis:firefighting
Ø effectivelycontrolinflammation
Ø eliminateorreducetheriskofvisionlossfromstructuralandfunctionalcomplicationsthatresultfromuncontrolledinflammation
Includes
ì topicalcycloplegics,
ì topicalorsystemicnonsteroidalanti-inflammatorydrugs
ì topicalorsystemiccorticosteroids
MydriaticandCycloplegicAgents
ì beneficialforbreakingorpreventingtheformationofposteriorsynechiae
ì forrelievingpainfromphotophobiasecondarytociliaryspasm
§ cyclopentolatehydrochloride1%§ Atropine1%§ Homatropine2%§ Tropicamide0.5%
SteroidsandNon-SteroidalTargets
Corticosteroids:mainstayofuveitistherapy
ì treatmentofactiveinflammationintheeye
ì preventionortreatmentofcomplicationssuchasCME
ì reductionofinflammatoryinfiltrationoftheretina,choroid,oropticnerve
Topicaladministration
ì Prednisiloneacetate(PF)
ì Durezol(0.05%difluprednateophthalmicemulsion)QID=Q2HPF
NonsteroidalAnti-InflammatoryDrugs
ì workbyinhibitingcyclooxygenase(COX)isoformsland2or2alone
ì reducethesynthesisofprostaglandinsthatmediateinflammation
ì Ketorolacand2neweragentsbromfenacandnepafenac-usedforthetreatmentofCME.
PeriocularSteroidadministration
ü moreposterioreffectisneededor
ü Noncompliance
ü unresponsivetotopicalorsystemicadministration.
ü preferredforintermediateorposterioruveitis
ü preferredforCME
X
PeriocularSteroidcontraindicated
ì casesofinfectiousuveitis(eg,ARN)
ì necrotizingscleritis
ì Steroidresponders
ì Advancedglaucoma
ì Questionablefollowup
Complications:
§ ElevatedIOP
§ Subconjunctivaledema
§ Subconjunctivaldeposits
§ Eyeliddiscoloration
§ perforation
Systemicadministration
ì supplementorreplaceotherroutesofadministration
ì vision-threateningchronicuveitiswhentopicalcorticosteroidsareinsufficient
ì Ifcorticosteroidtherapyisrequiredforlongerthan3months.Immuno-modulatorytherapy(IMT)isindicated
Intravitrealadministration
Triamcinoloneacetonide4mg(0.1mL)
ì "sterileendophthalmitis“
ì Infectiousendophthalmitisandrhegmatogenousretinaldetachment
Ozurdex(sustainedreleaseDexamethasone0.7mg)
ì MultipleinjectionsincreasetheriskofcataractandlOPelevation
IntravitrealAnti-VEGFmedication(Avastin,Lucentis)
ü Off-labelforCMEwithoutriskofcataractorglaucoma
Retisert(sustained-releasefluocinoloneimplant0.59-mg)
ì uniformincreasetheriskofcataractandhighrateofglaucoma
lmmunomodulatoryandanti-TNFMedications
ì severe,Sight-threateninguveitis
ì whoareresistanttoorcannottoleratecorticosteroids
ì inhibitingorreducinglymphocytesorgrowthfactors/modulatorsthatareresponsiblefortheinflammation
Guidedapproach
History Exam Diagnostic Treatment Response
AdditionalDiagnostic
Mondaymorningredeye
ì 25yearoldfemalewith1weekhistoryofredrighteye
ì 1weekdullpainrighteye,madeworsewithlightandtouch,triedVisineandmother’s“eyedrops”(unknown)
ì deniesrecenttraumaorcontactlensuse,pastocularormedicalhistory
ì worksasasecretaryinabusinesswithnegativesocialhistoryandfamilyhistory
Mondaymorningredeye
ì VA20/40ODand20/20OS
ì external:redrighteye
ì corneaclear,nostain
ì ACdeep,2+cells,lensclear
ì patientdefersdilation,OPTOSnormal
Treatment:
ì PrednisiloneacetateQID
ì return1-2weeks
Mondaymorningredeye
ì VA20/40ODand20/20OS
ì external:redrighteye
ì corneaclear,nostain
ì ACdeep,2+cells,lensclear
ì patientdefersdilation,OPTOSnormal
Treatment:
ì PrednisiloneacetateQID
ì return1-2weeks
Mondaymorningredeye:Return4dayslateronFridayat3PM
Redeyeandsymptomsareworse,takingPrednisiloneacetateandVisine
ì VA20/60ODand20/20OS
ì externalredrighteye
ì corneaclear,nostain
ì ACdeep,3+cells,lensclear
ì refertoretinaformanagement:SAMEDAYretinaexamconcurs
Mondaymorningredeye:Return4dayslateronFridayat3PM
Redeyeandsymptomsareworse,takingPrednisiloneacetateandVisine
ì VA20/60ODand20/20OS
ì externalredrighteye Anyotherideasbeforereferral?
ì corneaclear,nostain
ì ACdeep,3+cells,lensclear
ì refertoretinaformanagement:SAMEDAYretinaexamconcurs
Durezol™:Difluprednateophthalmicemulsion0.05%
ì topicaldiflurinatedderivativeofprednisolone
ì ElevationofIOP3%postoperatively
ì Onset1-2weeks
Uveitis:QIDDurezol=PredForte8x/dayì 80%ofchildrenand45%ofadultsexperiencedelevatedIOPof≥10mmHgì 60%ofchildrenand18%ofadultshadapeakIOPof≥30mmHgì 5%ofadultsexperiencedanIOPof≥50mmHg
AnteriorUveitis
ì Multipleetiologies
ì Mosttypesofanterioruveitisaresterileinflammatoryreactions
ì 38%-60%areidiopathic
ì HLA-B27positiveorHLA-B27–associateddiseasescomprisethenextlargestpercentage(17-41%)
ì <10%“therest”
AnteriorUveitis:Etiology
ì Lymedisease:deertick,history
ì Sarcoidosis:nodules,SOB,race
ì Behcets:aphthous,genitalulcer,hypopyon
ì Syphilis:history,HIV
ì Medications:rifabutin,Etidronate(Didronel)metipranolol,(OptiPranolol),latanoprost(Xalatan))
ì TB:drugabuse,3rdworld,immunodeficient
ì Fuchsheterochromiciridocyclitis:Heterochromia,diffusestellatekeraticprecipitate,unilateral
SystemicCausesofAnteriorUveitis: MondayMorningRedEye
Non-infectiousHLA-B27associateddiseasesSarcoidosisSyphilisMSCollagenVascularDiseaseassociated
CASE1
Mondaymorningredeye
ì testingforHLA-B27negative
ì ANAnegative,sedratenormal
ì negativeLymetest
ì negativeRPR
ì furtherhistory-Scandinavian,additionaltestingpositive,elevatedACE,butnegativeLysozyme,negativechestX-rayandnoindicationofsystemicdisease:equivocal
ì mother’sdropsrelatedtocataractsurgery
Treament: DurezolQIDandIllevroQD
Mondaymorningredeye
ì Longdiscussionofuveitis,non-compliance,complicationsofnon-complianceanduveitis
ì baselineOCT,OPTOS
ì DurezolQIDandIllevroQDfor1monthandtaperover2monthswithmaintenanceonIllevrofor3months,thenq3monthmonitoringfirstyear
CASE1
Postopchallenge: 72yearoldCaucasianmale:postopcataractIOLOS 1MonthPostOp
ì NearlyfinishedwithtaperofDurezolandIllevro(stillonDurezolQDandIllevro)
ì VAwas20/25OSonpresentation(was20/20previous)
ì AC“tracecell”
ì IOP10
ì IOLinposition,notdilated*
ì Doctor’sPlan:restartDurezolQIDdropsandseeaweeklater-butcomesbackwithpersistentACreactionandnochangeinvisualacuity.Referredforlackofresponsetotreatment.
CASE3
Postopchallenge
ì recurrentpostoperativeanterioruveitisonDurezolandIllevro,restartedDurezolQIDdropsandseenaweeklater
ì VAslightlyreducedfrom20/20to20/25OS
ì AC“tracecell”
ì IOP10
ì anyothertests?Trialofothermeds?Refer?
CASE3
Postopchallenge
ì dilatedexam:novitreousatIOLedgeorinAC,novitreouscell,retinalexamnormal
ì OCTnormal ?validityoffluoresceinangiogram
ì discussedcompliance
ì discussedincreasedDurezolto6XdayandBromsiteBID
ì anteriorsubTenon’scapsuleinjectionofTriamcinolone
ì chosethedrops-followup1week,toldtocallifworse(alwaysworryaboutlateonsetendophthalmitis:Pacnes)
CASE3
Postopchallenge
ì improvedonDurezolto6XdayandBromsiteBID:VA20/20,nocell
ì re-stressedcompliance,return1week
ì stable:continuedDurezolQID,BromsiteBIDreturn1week
ì stable:continuefor3-4weekthentaperover2monthswithmaintenanceonIllevrofor3months
ì returntoreferraldoctorformonths2and3
ì thenq3monthmonitoringfirstyear systemictestingordisease?
CASE3
RetinaCase:theyoungprofessional
§ 35yearoldwhitemalereferredfor“recurrentiritis”
§ Acuteonsetrighteyepain,unrelievedwithPredForteQID
§ 20/40 : 20/20 TA:20 :15
§ ACOD:10cells/hpf,1+flare,normaliris,lensposteriorsegmentnormal
§ Eyeinjectionblancheswith2.5%Neo
RetinaCase:theyoungprofessional:PLAN?
§ Testing?
§ Noassociatedsymptoms
§ ROSnegative
§ Treatment?
RetinaCase:theyoungprofessional:PLAN?
§ PredForteorDurezol?
§ NSAID:ketorolacvs.ProlensaorIllevro?
§ Cycloplegic?
§ Followup?
RetinaCase:theyoungprofessional:Course
§ PFQID—worseat1week,increasefrequency?
§ Switchsteroid?
§ AddNSAID?
§ Testing?
RetinaCase:theyoungprofessional:Course
§ switchedtoDurezolQID-for1monthandaddedIllevroforpain
§ 1weekfollowupIOP43
§ ContinueDurezol?
§ Whichglaucomamedicinetouse?
§ ConsiderSLTifquiet?
Steroid-inducedOHT
1)Nonresponders:~67%ofthepopulationì IOPincreasesof<6mmHgì IOPlowerthan20mmHg
2)Moderateresponders:<30%ofthepopulationì IOPincreasesof6-15mmHgì IOPbetween20and31mmHg
3)Highresponders:4%to6%ofthepopulationì IOPincrease>15mmHgì IOP>31mmHg
β-Blockers,α2agonists,andcarbonicanhydraseinhibitorshaveallbeenshowntoeffectivelycontrolsteroidinducedOHT
RetinaCase:theyoungprofessional:Course
§ ControlledonDurezol,IllevroandAlphagan
§ Durezoltaperedover2months
§ WhentostopAlphagan?
§ continueIllevro?
§ Followup?
RetinaCase:theyoungprofessional:Course
§ 4monthfollow-upreturnswithsomebreakthroughACcell:restartedonDurezolandIllevrofor1month,taperedover2andleftonIllevro
Recurrent Repeatedepisodesseparatedby
periodsofinactivitywithouttreatment >3months‘duration
Chronic Persistentuveitiswithrelapse<3monthsafter discontinuingtreatment
RetinaCase:theyoungprofessional:PLAN?
§ Testing?
§ Repeathistory,arthritisandbackpainandarthritisrunsinthefamily
§ Likestohikeinthewoods
RetinaCase:theyoungprofessional: HISTORY
Recreational/Occupationalactivities§ swimming:leptospirosisand
trematodegranulomas§ dogorcatowners:Toxoplasma&
Bartonella,Toxocaracanii§ Hikers/hunters:Lyme,WestNile§ Plumbersandsewerworkers:
leptospirosis§ Cattle/slaughterhouse:
Leptospirosis,cysticercosis§ Pigs/slaughterhouse:Cysticercosis,
Leptospirosis§ Prostitute/IVDrug:syphilis,TB
§ Age§ Children:JRA,Toxoplasmosis§ Youngadults:HLAB-27,MS,Behcet's§ Older:post-cataract,Zoster
§ Gender§ Males:Ankylosingspondylitis,Reiters,Behcet's,§ Females:Rheumatoidarthritis,JRA,collagenvascular
§ Race§ Caucausian:Ankylosingspondylitis,Reiters§ AfricanAmerican/Scandinavian:Sarcoid§ Asian:VKHsyndrome§ Greek/Turkish:Behcet's
RetinaCase:theyoungprofessional:SYSTEMICSYMPTOMS§ Musculoskeletal
Arthralgias/arthritis-Behçetdisease,sarcoidosis,SLE,juvenileidiopathicarthritis(JIA),Lymedisease,syphilis,psoriaticarthritis,Reitersyndrome,ulcerativecolitisSacroiliitis-Ankylosingspondylitis,Reitersyndrome,inflammatoryboweldisease
§ ConstitutionalFever-Reitersyndrome,Behçetdisease,PAN,inflammatoryboweldisease,HIV,tuberculosis,coccidioidomycosis,Whippledisease
Nightsweats-Malignancy,tuberculosis,sarcoidosis,coccidioidomycosisFlulikesymptoms-APMPPE,multipleevanescentwhitedotsyndrome(MEWDS),autoimmunehepatitis
§ Genitourinary§ Genitalulcers-Behçet,Reitersyndrome,syphilis§ Hematuria-Wegenergranulomatosis,PAN,SLE§ Circinatebalanitis-Ankylosingbalinitis,Reitersyndrome§ Urethraldischarge-Reitersyndrome,syphilis§ Nephritis-PAN,Wegenergranulomatosis,tubulointerstitial
nephritisanduveitis(TINU)§ Epididymitis-PAN,Behçetdisease,Reitersyndrome
§ Dermatologic§ Alopecia-VKHdisease,syphilis§ Vitiligo,poliosis-VKHdisease§ Nodules-Sarcoidosis,Lupus,Crohn’s,ulcerativecolitis§ Rash-Syphilis,Lymedisease,Reitersyndrome,leprosy,sarcoidosis,
herpeszoster,Behçetdisease,psoriasis,SLE,Kawasaki§ Keratodermablennorrhagicum-Reitersyndrome,ankylosing
spondylitis§ Erythemanodosum–Behçet’s,sarcoidosis,APMPPE
RetinaCase:theyoungprofessional:Course
Testing:
1. Purifiedproteinderivative(PPD)skintestorQuantiferonGold
2. serumangiotensin-convertingenzyme(ACE)
3. Syphilisserologies
4. HLA-B27
5. ChestX-rayorCTandhipX-rays
6. Lymeserology
AnteriorUveitis:HLA-B27
ì ontheshortarmofchromosome6
ì presentin1.4-8.0%ofthegeneralpopulation;
ì present50-60%ofpatientswithacuteiritis
ì seronegative(RFnegative)spondyloarthropathiesassociated
ankylosingspondylitis,Reitersyndrome,inflammatoryboweldisease,psoriaticarthritis,andpostinfectiousarthritis(Whipple’sDisease)
RetinaCase:theyoungprofessional:Course
ì PlacedbackonDurezol,IllevroandAlphagan
ì UnabletototallyweanoffDurezol
ì Furthertesting?
ì Therapeuticoptions?
RetinaCase:theyoungprofessional:Course
ì Consultwithhisprimarymedicaldoctorandrheumatologist
ì Placedonadalimumab,administered40mgsubcutaneouslyevery2weeks,substantiallyimprovedhissymptoms
ì TaperedDurezolover2monthsagain,discontinuedIllevroafter3months
ì Recurrencefreeat1year
TheFrequentFlyer42yearoldAfricanAmericanfemale,accountant:
-Threedayhistoryofredrighteye,similarepisode2monthsprevious
-Heroptometristwhostartedonheron1. DurezolQIDOU(hadbeenonPrednisiloneAcetate)2. CyclopentolateOUBIDweekforiridocylcitis3. VAwas20/20OUonpresentation,nowdiminishing
ì Improvedpainandvisionsincestartingdrops-referredforlackofresponsetotreatment
ì claimsthatshehadbloodworkandradiologystudiesandallresultswere“normal”
CASE2
FrequentFlyer: Examination3/30/2015correctedva
OD:20/80phni
SLE:
ì pigmentedmediumkeraticprecipitateslower1/3ofcornea
ì PS1-2:30,3:30-5,8-9
ì 1-2+NS,PSC
IOP:12
OS:20/70ph20/40
ì pigmentedmediumkeraticprecipitateslower1/3ofcornea
ì noPS
ì 1+NS
IOP:12
*patientwasnotdilatedbyherreferringeyedoctor
CASE2
FrequentFlyer:
[Recurrent,bilateralgranulomatousanterioruveitisonDurezolQIDOUandPrednisiloneAcetateinthepastì VAwas20/20OUonpresentationnowdiminishedto20/70and
20/40
ì claimsthatshehadbloodworkandradiologystudiesandallresultswere“normal”
ì anyothertests?Trialofothermeds?Refer?
CASE2
FrequentFlyer: Examination3/31/2015
2+vitreoushazeandcell
CME
Epiretinalmembrane
Bluntedfovealreflex
Novasculitis
Nosnowbanking
Tracevitreoushaze&cell
NoCME
Epiretinalmembrane
Novasculitis
Nosnowbanking
CASE2
FrequentFlyer:
Recurrent,bilateralgranulomatousanterioruveitisonDurezolQIDOUandPrednisiloneAcetateinthepast
ì HLA-B27,ANA,RPRandLymetiterwerenegative
ì elevatedACE,Lysozymewithmid-hilarnodulesonchestX-ray
ì granulomatousdiseaseofbronchialwashing+slightlyrestrictivePFTs
CASE2
SystemicCausesofAnteriorUveitis
Non-infectiousHLA-B27associateddiseasesJIA-associatedSarcoidosisBehcet’sdiseaseV-K-HdiseaseMSDrug-inducedMalignancy(metastases,leukemia,CNSlymphoma,retinoblastoma)
CASE2
IntermediateUveitis:
ì blurryvisionandfloaters
ì 80%bilateral,30%ofunilateralbecomebilateral
ì Visionloss
ì Early:vitritisandCME(28-50%ofallpatients)ì Late:uveiticglaucoma,retinaldetachment,chronicCME,NVDand
vitreoushemorrhageorthedevelopmentofanepiretinalmembrane.
IntermediateUveitis
ì 8-15%referralstotertiarycentersintheUS
ì 69%areidiopathic(HLA-DR2andHLA-DR15)
ì 22%havesarcoidosis
ì 8%haveMS(16%ofallMSpatients)
ì Lymedisease,
ì TB,syphilis,
ì IBD,Whipples
ì lymphoma
IntermediateUveitis:complications
ì opticnerveedema(50%pediatriccases)
ì CME(28-50%)
ì Glaucoma(independentofsteroids)
ì Cataract(15-20%)
ì Vasculitis
ì RD(3-20%)
IntermediateUveitis:workup
ì ErythrocyteSedimentationRate
ì TuberculinSkinTest
ì ACE(Angiotensin-Converting
Enzyme)
ì Lysozyme
ì LymeTiterandWesternBlot
ì RPR
ì FTA-ABSorMHA-TP
ì ChestX-Ray(PAandLateral)
althoughCTscansuperiorinSarcoid
ì MRICNSwithandwithoutcontrast
ì HLA-DR2andHLA-DR15
CMETreatment
1. Steroids:topically,periocularinjection,intravitrealororally
2. Non-steroidalanti-inflammatorydrugs(NSAIDs).NSAIDsalsoaffectprostaglandinsynthesisandmaybegiventopicallyororally
3. Carbonicanhydraseinhibitors:increasetheactivetransportoffluidfromtheretinatothechoroidsbyRPEpumpsbutedemarecurrswhenstopped
4. Anti-VEGFintravitrealinjection:offlabelbuteffective.Anti-IL6so
PROGNOSIS: CMErequiresmanymonthsoftreatment!VisualacuityimprovementifCMEislessthan6monthsdurationCMDsecondarytochronicCMEmayleadtopermanentvisualloss
frequentflyer: OCT3/30/2015 treatmentì Anterioruveitiswithspilloverorintermediate
ì Durezoldosing
ì Cycloplegic
ì Ozurdex
ì Treatinganteriorandposteriordisease:IGNvs.uveiticCME
frequentflyer:Examination4/6/2015
CORRECTEDVA
OD:20/50-PH
SLE:
ì pigmentedmediumkeraticprecipitateslower1/3ofcornea
ì PS1-2:30,3:30-5,8-9
ì 1-2+NS,PSC
IOP:30
OS:20/40-PH20/25+
pigmentedmediumkeraticprecipitateslower1/3ofcornea
ì noPS
ì 1+NS
IOP:21
Examination4/6/2015
2+vitreoushazeandcell
CME
Epiretinalmembrane
Bluntedfovealreflex
Novasculitis
Nosnowbanking
3/30/2016
2+vitreoushazeandcell
CME
Epiretinalmembrane
Bluntedfovealreflex
Novasculitis
Nosnowbanking
4/6/2016
Ozurdex
CME:iritisvs.parsplanitisorpanuveitis
ì firstdescribedbyIrvine(1953)withdecreasedvisualacuityassociatedwithprolapseofvitreousintheanteriorchamberafterintracapsularcataract
ì decreasedvisioninmanyophthalmicdiseases
ì mostcommonmacularchangeinuveitis(andcauseofdecreasedvision)
ì Parsplanitis,iridocyclitis,Birdshot,SarcoidosisandHLA-B27associateduveitis
Ozurdexextended-releasedexamethasoneintravitrealimplant0.7mg
11.3%ofpatientswithincreasedIOPof10mmHgì PeakIOPoccursatapproximately6weeksì Fallsbacktobaselineby16weeksì 7.9%>35mmHg
IOPmanagedwithtopicalmeds
0.6%donotrespond
1.3%requiresurgery
OCT4/6/2015treatment
ì Durezolreduced:howtotaper?
ì Cyclogil:needforcontinuation?
ì TreatingIOP:singlevs.dualtopical?
4/20/2015 VAOD:20/30OS:20/20
SLE:noiritis IOP-OD:21 OS:16
6/1/2015 VAOD:20/40OS:20/30
SLE:noiritis IOP-OD:20 OS:22
6/29/2015 VAOD:20/30OS:20/20
SLE:noiritis IOP-OD:19 OS:19-Durezoltapered
8/8/2015 VAOD:20/30OS:30/20
SLE:noiritis IOP-OD:25 OS:19-Durezolqday,offofCombiganandDurezol8/25
8/24/2015 VAOD:20/30IOP-OD:15
10/19/2015 VAOD:20/40 OS:20/20
SLE:noiritisIOP-OD:18 OS:18–nomeds
11/30/2015 VAOD:20/60 OS:20/25
SLE:1+iritisIOP-OD:15 OS:13
-Durezol,CombiganrestartedandOzurdexgiven
12/21/2015 VAOD:20/40 OS:19
SLE:1+iritispersists-Durezol,Combigancontinued
01/11/2016 VAOD:20/40 OS:20/25
SLE:resolvediritisIOP-OD:17 OS:20
03/07/2016 VAOD:20/40 IOP-OD:28
SLE:recurrent1+iritis –Durezolincreased
3/29/2016 VAOD:20/30OS:21SLE:iritisresolved-Durezol,Combigancontinued4/29/2016:glare,reducedvisionOD>OS
VAOD:20/30OS:20/20|IOPOU:18|resolvediritis
FutureManagementIssues
ì Recurrentuveitis-medicalworkup/management
ì Cataract-uveitismanagement
ì CME-furthertreatment,implicationsforcataractsurgery
ì MacularPucker-implicationsforcataractsurgeryandvisualresults,progressionwithuveitis,implicationsforCME