A case of fungal keratitis A clinical and in vivo confocal microscopy assessment.docx
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AcaseoffungalkeratitisAclinicalandinvivoconfocalmicroscopyassessment
Acaseoffungalkeratitis:
Aclinicalandinvivoconfocalmicroscopyassessment
WilliamL.Miller,a,,AmberGaumeGiannoniaandJudithPerrigina
aUniversityofHouston,CollegeofOptometry,505J.DavisArmisteadBuilding,Houston,TX77204–2020,UnitedStates
Availableonline1July2008.
Abstract
Apresumedcaseoffungalkeratitisispresented.Confocalimageshighlighttheadvantageofusingsuchtechnologytofollowtherapeuticprogress,particularlywhenstandardlaboratorytestingisinconclusive.Thiscasealsodemonstratestheimportanceofcontinuedpatienteducationregardingoverallcomplianceandlenscare.
Keywords:
Fungalkeratitis;Confocalmicroscopy;Contactlenses;Contactlenssolution
ArticleOutline
1.Background
2.Casereport
3.Discussion
Acknowledgements
References
1.Background
Thecorneaisequippedwithseveralprotectivemechanismstodefenditselffrommicrobiologicalandfungalinfection.Foravarietyofreasons,thisprotectioncanbeweakenedoroverwhelmed,resultinginanulcerativekeratitis.Commoncausativeagentsformicrobialkeratitisincludebacteria,viruses,acanthamoebaandfungus.Erieetal.[1]reportedtheincidenceofulcerativekeratitisintheUnitedStatesasapproximately11in100,000,howeveranotherreportstudiedcasesfrom1969to1998andfoundanincidenceofinfectiouskeratitisat3.1in1000clinicalvisits[2].Asynopsisofcontactlens-relatedcomplicationsworldwideindicatesthatgaspermeablecontactlensescarrythelowestriskofmicrobialkeratitis,withextendedwearsoftcontactlensescarryingamuchhigherrisk[3].Incidentratesformicrobialkeratitisrangefrom9.3to20.9per10,000.Thisriskiselevatedevenwhenthepatientiswearingasiliconehydrogel(SiHy)softcontactlensinanextendedwear(EW)modalityalthoughitislessthanEWhydrogelsoftcontactlenswearers[3]and[4].AlthoughelevatedinEWSiHy,theriskhasbeenshowntobedifferentwhencomparingnon-severecasesofkeratitistoseverecaseswiththeformerbeingnearlyzerowhiletherelativeriskofanon-severekeratitisisaround4.0[4].Oftheetiologiesknowntocausemicrobialkeratitis,fungalentitiesaretheleastlikely,comprisingbetween6%and20%ofcases[5].Fungalinfectionisalsorelativelyrareincontactlenswearers,typicallyconstitutingabout5%ofallcornealinfections[6],[7]and[8].However,aresurgenceoffungalkeratitiscasesoccurredin2005and2006,evenintheNorthwestUnitedStatesandtheWestCoast,whichhadnotpreviouslybeenseenasregionspronetofungalcornealinfection.Theincidenceduringthistimeperiodwas2.35per10,000contactlenswearersandincludedamongthefactorsrelatedtotheincreasingnumberswerepatientcomplianceandcontactlenscaresystems[9],[10]and[11].Somesuggestthatupto30%offungalkeratitiscasesalsohaveanassociatedbacterialinfection[12].
2.Casereport
A24-year-oldmalewasimmediatelyreferredtotheUniversityEyeInstitute(UEI)byanearbyUniversityhealthcenterinOctoberof2007forfullcareofa“paracentralcornealulcerOS.”Hereportedawakingtolefteyeirritationaftera2 hnap48 hpriortohisvisittotheUEIwhilewearinghis2week-oldAcuvueOasys(senofilconA)siliconehydrogelcontactlenses.Afterlensremoval,herepeatedlysplashedtapwaterintohiseye,butstoppedafterexperiencingtremendouspain.Hesubsequentlydisposedofthispairoflensespriortovisitingourclinic,sothelenseswerenotavailableforvisualinspectionormicrobiologicalanalysis.Hereportedoccasionalextendedwearanddiscardedhislensesevery2weeks.Thepatientalsodeniedtraumatotheocularsurface.Hiscurrentcontactlenscasewas6monthsoldandhehabituallyusedeitherRenuMultiplusorRenuwithMoistureLocmulti-purposecontactlenssolutionfordailycleaningandsoakingofhislenses.Thepatientreportedseverepainwithtearinganddeniedrecentactivityaroundlakes,poolsorotherbodiesofwater.Inaddition,hewascurrentlytakinghydrocodone/acetominophen(Vicodin)asneededforpain,asprescribedbythehealthcarecenterphysician.
Thepatient'senteringSnellenvisualacuity(VA)wasnotattainableduetoseveretearing.Despitemildblepharitis,examinationofhisrighteyewasunremarkable.Biomicroscopyofhislefteyerevealedsevere,diffusebulbarinjection,acentralcornealulcerand4clustersofperipheralinfiltrates(Fig.1).Amoderateamountofcornealedemawaspresentandtheanteriorchamberwasquietwithoutevidenceofcells,flareorhypopyon.ThelesionwasscrapedwithaKimuraspatulaandthespecimenwasplatedonSabouraud'smediaandsenttoalabforprocessing.Thediagnosisatthatvisitwasacentralcornealulcerwithperipheralinfiltratesofunknownetiology.Thepatientwasinstructedtoalternatedropsoftobramycinandmoxifloxacin(Vigamox)every30 minandtousebacitracinointmentatnightinthelefteyeonly.In-officedropsofVigamoxand0.25%Scopolamineweregivenandhewasaskedtoreturnin24 h.
Fig.1. InitialvisittotheUniversityEyeInstitute.Biomicroscopydemonstratestheprimaryandsatelliteinfiltrativelesions.(Mainannularlesion,arrowssignifyrepresentativesatellitelesions.)Bulbarconjunctivalgrade4hyperemiaisalsoevidentinthebiomicroscopicbeam.
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Thenextday,thepatientreportedadheringtotheprescribedmedicationregimenandstatedthatalthoughhiseyewasstillveryredandthevisionwaspoor,hewasexperiencinglesspainandtearing.EnteringVAwas20/70−1inthelefteyewithhabitualspectacles.Allinfiltratesremainedflatandshowedslightimprovementfromthepreviousvisit.Agrade4(CCLRUscale)conjunctivalhyperemiawasstillpresent[13].Hewasinstructedtocontinuewiththecurrentcourseoftherapyandreturnin2days,orsoonerifsymptomsworsened.HewaseducatedonthepossibilityofcentralscarringandpermanentreductionofVA.
Thepatientwasseenfivetimesoverthenextweek,includingavisittoacornealspecialistwhore-culturedthelesionsontwodifferentoccasions.Invivoconfocalmicroscopy(Confoscan3,Nidek,GreensboroNC)wasalsoperformedatthestartofthisvisitsequencetimedemonstratinghyper-reflectivebranchinghyphae-likebodiespresentintheanteriorstroma(Fig.2aandb).Thewidthofthebranchinghyphaeappearedtobebetween5and10 μmwhichisconsistentwithwhatisfoundwithfungalagents.Theinvivoconfocalimagesweresuggestiveofthefusariumspecies.Inaddition,thecontactlenscaseandsolutionbottlewerealsocultured.Fig.3showsthestatusofthepatient'ssolutionbottlewithevidentnon-complianceinboththecaseandbottle.Apositiveresultforfungalgrowthwasneverobtainedonanyculturedmedia;however,theophthalmologistaddednatamycin5%(Natacyn)every2 htothecurrenttreatmentregimenduetoahighsuspicionthattheinfectionwasfungalinnature.Biomicroscopyandconfocalmicroscopyshowedaslightimprovementintheinfiltrativeresponseatthe1weekvisit.(Fig.4aandb).
Fig.2. (a)Confocalimagesoftheanteriorstroma.Hyper-reflectiveareasrepresentinghyphaearepresentduringthereturnvisitsinweek1.(Arrowsshowfungalhyphae,shortenedarrowdemonstrateshyphaebranchingandstarsindicaterepresentativekeratocytesinthefield.)(b)Confocalimagesofthebasalepithelium/anteriorstromademonstratinginfiltratesduringthereturnvisitsinweek1.(Longarrowshowscornealinfiltrateswhiletheshortenedarrowshowsbasalepithelialcells.AsuspectedLangerhancellislocatedattheasterisk.)Imagesectionrepresentsanobliqueviewshowingbasalepithelialcellsinthelowerleftandanteriorstromaontheupperright.
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Full-sizeimage(39K)
Fig.3. Solutionusedbythepatientexhibitingasoiledlidandcaptop.
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Fig.4. (a)Oneweekafterinitiationofantifungaltherapy.Imagedemonstratesthatthesatellitelesionsaredecreasinginintensityanddensity.(b)Confocalimagesshowingscarringandresidualinfiltratesatthelevelofthebasalepitheliumafter1weekofantifungaltreatment.
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Thispatienthad13additionalvisits(November2006throughMarch2007)overthenextseveralmonthsandcontinuedtoshowextremelyslow,butsteadyimprovementateachexamination.Hisrightspectaclelenswasupdatedtoprovidethebestpossiblevisionduringthelongcourseofhealing.Invivoconfocalmicroscopywasperformedseveraltimesthroughoutthisperiod.Itrevealedhyphae-likehyper-reflectivelinearstructuresthroughoutthesub-epithelialandanteriorcornealstromathatslowlylessenedinquantityanddensityduringthecourseofhealing.Thehyper-reflectiveintensityofeachhyphaealsodecreasedoverthecourseofthesemultipleconfocalexams.
BylateNovember,allcorneallesionswerealmostfullyhealed,althoughsub-epithelialcornealscarswerepresent(Fig.5aandb).Fig.5bshowsthatthedensityofthescarringhadintensifiedandgrownlargerwhencomparedwithFig.4b.Fig.5cshowsthatveryfewresidualhyphaeremainedasevidencedwithconfocalmicroscopy.TobramycinandVigamoxweredecreasedtofourtimesperdaywhileNatacynwasreducedtothreetimesperday.ThereductioninNatacynwasnecessarytodecreasethemedicamentosaeffectswhichwereaffectingthecornealsurfaceandtheultimatevisualoutcomeofthepatient.Itwasfeltthatsincesofewhyphaeremainedandtheirhyper-reflectivitywasdecreasedthebenefitofdecreasingthedosageoftheNatacynoutweighedtheriskofpossiblereactivitation.
Fig.5. (a