A case of fungal keratitis A clinical and in vivo confocal microscopy assessment文档格式.docx

A case of fungal keratitis A clinical and in vivo confocal microscopy assessment文档格式.docx

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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.

ViewWithinArticle

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.

Full-sizeimage（39K）

Fig.3. 

Solutionusedbythepatientexhibitingasoiledlidandcaptop.

Fig.4. 

（a）Oneweekafterinitiationofantifungaltherapy.Imagedemonstratesthatthesatellitelesionsaredecreasinginintensityanddensity.（b）Confocalimagesshowingscarringandresidualinfiltratesatthelevelofthebasalepitheliumafter1weekofantifungaltreatment.

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