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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  external:redrighteye



ì  patientdefersdilation,OPTOSnormal

Treatment:

ì  PrednisiloneacetateQID

ì  return1-2weeks

Mondaymorningredeye:Return4dayslateronFridayat3PM

Redeyeandsymptomsareworse,takingPrednisiloneacetateandVisine


ì  externalredrighteye



ì  refertoretinaformanagement:SAMEDAYretinaexamconcurs

Mondaymorningredeye:Return4dayslateronFridayat3PM

Redeyeandsymptomsareworse,takingPrednisiloneacetateandVisine


ì  externalredrighteye Anyotherideasbeforereferral?



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?


§  PredForteorDurezol?

§  NSAID:ketorolacvs.ProlensaorIllevro?

§  Cycloplegic?

§  Followup?

RetinaCase:theyoungprofessional:Course

§  PFQID—worseat1week,increasefrequency?

§  Switchsteroid?

§  AddNSAID?

§  Testing?


§  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


§  ControlledonDurezol,IllevroandAlphagan

§  Durezoltaperedover2months

§  WhentostopAlphagan?

§  continueIllevro?

§  Followup?


§  4monthfollow-upreturnswithsomebreakthroughACcell:restartedonDurezolandIllevrofor1month,taperedover2andleftonIllevro

Recurrent Repeatedepisodesseparatedby

periodsofinactivitywithouttreatment >3months‘duration

Chronic Persistentuveitiswithrelapse<3monthsafter discontinuingtreatment


§  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


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)


ì  PlacedbackonDurezol,IllevroandAlphagan

ì  UnabletototallyweanoffDurezol

ì  Furthertesting?

ì  Therapeuticoptions?


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  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  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


CME

Epiretinalmembrane

Bluntedfovealreflex

Novasculitis

Nosnowbanking

3/30/2016


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