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ReviewofOphthalmology>WinningtheBattleAgainstCornealUlcers

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NEWSLETTERS

WinningtheBattleAgainstCornealUlcers
Fourexpertssharetheirknowledgeandexperiencedealingwith
thesesightthreateninglesions.
ChristopherKent,SeniorEditor
9/5/2013

Cornealulcersareacommonproblem,oftenencounteredbyeyecareprofessionals.Unfortunately,anulcercanbedifficultto
diagnoseitscausecanbeelusiveandtheconsequencesofanerrorindiagnosisortreatmentcanbesevere.Knowingwhatto
lookforandcommonmistakestoavoidcanmakeallthedifference.

CommonEncounters
Themostcommontypeofulcercliniciansarelikelytosee,byfar,isabacterialulcer,saysJohnSheppard,MD,MMSc,
presidentofVirginiaEyeConsultants,professorofophthalmology,microbiologyandmolecularbiology,directorofresidency
researchtrainingandclinicaldirectoroftheThomasR.LeeCenterforOcularPharmacologyatEasternVirginiaMedicalSchool
inNorfolk,Va.Manyoftheorganismsthatcausebacterialulcershaveextremelypotenttissuedestructivemechanisms,soits
alwaysimperativethatbacterialkeratitisisidentifiedandtreatedrapidly.Pseudomonas,inparticular,createsproteolytic
enzymeslikecollagenasethatrapidlydegradetissuesitsknownforcreatingulcersthatleadtoperforations.
ThenumberoneriskfactorforcornealulcersintheUnitedStatesiscontactlensuse,hecontinues.Anotherkeyriskfactoris
trauma.Cornealulcersaremorecommonamongthoseinindustrialoroutdooroccupations,andbeingolderincreasesyourrisk
particularlyinthecaseofaveryoldpatientwhohaschronicblepharitis.Diabeticsareatgreaterrisk,asarepatients
sufferingfromdryeye.Latitudeisimportantthewarmertheclimatethemorelikelyyouaretodevelopanulcer,andthemore
likelyyouaretodevelopafungalulcer.InVirginiaweseemorefungusthaninBostoninFloridatheyseemorethanwedo.

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Anotherulcerthatcliniciansoftenrunintoistheperipheralcornealulcer,saysJohnR.Wittpenn,Jr.,MD,partnerat
here.
OphthalmicConsultantsofLongIslandandassociateclinicalprofessorofophthalmologyattheStateUniversityofNewYorkat
StonyBrook.Thisisntsomuchanulcerasitisatypeofkeratitis,aninflammatoryproblemassociatedwithstaphylococcusovergrowthinthelid.These
individualspresentwiththeclassicperipheralinfiltrate.

Iftheresadefect,Irecommendtreatingitasaninfectiousulceruntilprovenotherwise,hecontinues.Butiftheepitheliumisfullyintactandtheresnoreacti
intheanteriorchamber,thatsphlyctenularkeratitis,aninflammatoryproblem.YoushouldaddressthelidswithsomethinglikeAzaSite,whichhasgreat
penetration,oratopicalointmentappliedtothelidmarginsatbedtimeinconjunctionwithanantiinflammatory.Ihappentolikeloteprednolbecauseitsavery
goodsurfaceantiinflammatorywithaverylowriskofpressureelevation.Butyoucouldalsouseafluorometholoneorsomethingsimilar.

Ofcourse,thedifficultyoftreatmentandlikelihoodofapositiveoutcomeareprofoundlyaffectedbyhowquicklythecornealulcerisdetectedandtreated.Whe
patientcomesinearly,evenwithavirulentorganism,iftheinfectionislimitedtotheanteriormostpartofthecorneaandthepatientistreatedintensivelywith
appropriatetopicalantibiotics,hemightendupwithcompleteresolutionoftheinfectionandjustasmallanteriorcornealscar,notesThomasJohn,MD,clinical
associateprofessoratLoyolaUniversityatChicago.However,ifthepatienthasacompromisedcorneaandpresentslaterwithalargecornealulcer,eveninth
bestscenariothatcanpotentiallyresultinalargecornealscar.

Dr.Sheppardpointsoutthatthisissuecanbeexacerbatedbycontactlenses.Acontactlensmayactuallymitigatetheinitialsymptomsofanulcer,hesays.A
result,thepatientmayleavethecontactlensontomakeitfeelbetter,therebydelayingpresentationtotheophthalmologistoroptometrist.

IdentifyingtheOrganism

CharlesStephenFoster,MD,FACS,FACR,clinicalprofessorofophthalmologyatHarvardMedicalSchool,andfounderandpresidentoftheMassachusettsEye
ResearchandSurgeryInstitutioninCambridge,pointsoutthatwhenapatientpresentswithacornealulcer,anumberofquestionsshouldbeaskedtodetermin
thediagnosisandareasonablefirstlinetreatment.
Idontstronglypromotetheideaoftryingtomakeacategoricaldiagnosisonthebasis
ofclinicalfeatures,butthereareafewcluesthatcanhelp,hesays.Istheulcer
peripheral,nearthelimbus,orisitmorecentralorparacentral?Isitjustaninfiltrateor
atrueulcer?Ifitsinfectious,isitbacterial,viral,fungalorparasitic?Isthepatients
cornealsensibilityintactordiminished?Doesthepatienthavenormallidfunction?If
not,isthisanexposureproblem?Isthepatientlyingasleepatnightwiththelidsopen,
thecorneadryingoutandtheepitheliumbreakingdown?Isitaneurotrophicproblem
causedbynervedamage?Testingbothcorneasforsensationoftouchcanbevery
enlighteninginthatregard.
Incasesofmicrobialkeratitisandstromalulceration,inadditiontoculturingthe
organism,therearecertainclinicalcuesandcluesthatcanbehelpful,hecontinues.
Theseincludeobviousfactorssuchasadischarge.Ifthereisadischarge,whatareits
characteristics?Isitwateryormorelikepus?Whatcolorisit?Ifthedischarge
resemblespus,doesithaveanodor?Pseudomonas,forexample,oftenhasa
characteristicsweetsmell.

Thelocationofacornealulcerisanimportantfactorindiagnosisand
treatment.Aboveleft:Acentralcornealulcerwithhypopyon.Above
right:Anaggressivechroniclimbalbacterialulcer(methicillinresistant
Staphylococcusepidermidis)withlimbalhypervascularity.(Allimages
courtesyJohnSheppard,MD,MMSc.)

Withfungustheresaninfiltrate,andtwoorthreeotherlittlewhitespotsnotconnectedtotheinfiltrate,henotes.Youmayseeabitofaplaqueonthe
endothelium,ontheinsidebehindthewhiteinfiltrate.Itsnotalwaysthecasethatafungusispresentwhenthosesignsexist,buttheindexofsuspicionwouldb
heightenedifonesawthosefeatures.

Dr.Fosteraddsthataherpeticulcerisanother,albeitlesscommonpossibility.Ifthepatienthashadherpesinthepast,evenifhecomesinwithsomethingth
doesntlooklikeaclassicdendriticepithelialdefect,hemaynonethelesshaveherpeticdiseaseratherthanabacterialdisease,hesays.Simplytestingcorneal
sensationatthatpointcanoftentellyoualot.Ifyoufindtremendouslydepressedsensation,thatmightindicateaneurotrophiculcer.Ifitisaneurotrophiculce
pursuingthewrongcoursehammeringitwithdrugsratherthanlubricationandmaybeabandagesoftcontactlensisonlygoingtomakeitworse.

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TakingaCulture

Ineverempiricallytreatatruecornealulceroraseriouslookinginfiltratewithoutharvestingmaterialfordiagnosis,saysDr.Foster.Henotesthatwhencultu
amicrobialulceritsimportanttoincludetheedgesandbaseoftheulcer,alongwithanydischarge,forsmearsonglassslidesandforplatingontovariouscultu
media.Ipersonallyliketwosplitplates,chocolateandbloodagar,hesays.Youmakestreaksoneachhalfofbothplatesthen,keeponeatroomtemperatu
andputtheotherinanincubator.Thisishelpfulbecausetheonekeptatroomtemperaturewillbeextremelygoodforgrowthoffungi.Illalsoplateonto
Sabroudsmediumforfungus,inadditiontosomethingforisolatinganaerobicbacteria.Whetherthatisthioglycolateoranotherbloodplateplacedinananaerob
incubatordependsonmylocationatthetime.

IfImsuspiciousthattheresaparasitelikeacanthamoebainvolved,theprocessgetsevenmorecomplex,he
continues.Inthatsituationthematerialhastobetransportedinsalineandthenplatedbythemicrobiologistto
cultureplatethatsalreadygrowingE.coli.Themostimportantthingistomakethishappeninatimelymanner.
necessary,havethepatientmeetyouatthehospitalemergencyroomanddoitthere,orreferthepatienttoan
eyeresidencyprogramiftheresonenearby.Theresidentoncallcantakecareofit.

Dr.Sheppardaddsthataculturecanbetakenfromtheconjunctivaandtheculdesacaswell.Theresagood
chancethattheorganismgrowinginthecorneawillbefoundinthoselocations,hepointsout.Also,withacon
lensuser,youmaybeabletoculturetheinfectiousorganismfromthecontactlenscase,ifthepatientbringsiti

Anearlymidperipheralcontactlensrelated
cornealulcercausedbyfluoroquinolone
sensitiveSerratiamarcescens.

Dr.Sheppardnotesthattherearevisualandtactilecluesthatmaysuggestaparticulartypeoforganismwhen
scrapingalargeulcer.Withagrampositiveorganism,youdontseetoomuchtissuenecrosis,hesays.Inste
yougetakindofsandyconsistencytotheulceratedcornealbed.Ontheotherhand,agramnegativeorganism
produceanecroticeffectwithlossofnormaltissueandalotofnecroticdebris,asoupyappearanceandmushy
feel.

Dr.Fosteraddsthatyoushouldneverwaitforthetestresultstobegintreatment.Startingtreatmentbeforeknowingtheresultsofthetestisstandardofcare,
says.

Dr.Fosternotesthatcliniciansfrequentlyaskwhethertheyshoulddoananteriorchambertapforaculturewhenapatienthasanulcerandahypopyon.That
badidea,becauseiftheulcerisbacterial,thehypopyonisalwayssterile,100percentofthetime,heexplains.Bacteriadontgetthroughanintactcornea.Th
hypopyonisareaction,notaninfection.Butinthecourseofdoingatap,onemayactuallydragbacteriaintotheanteriorchamber,inoculatingitandrisking
creatingacatastrophicendophthalmitis.

TheonlyinstanceinwhichIdconsideratapiswhereweveneverisolatedthemicrobethingsarenotgoingwellinfacttheyregettingworsetherearesom
featuresthataremakingusprettysuspiciousoffungusandtheprocessisgettingdeeperanddeeper.Iwilldoatapinthatsituation,becausefunguscanpass
throughanintactDescemetsmembrane.

ChoosinganAntibiotic
InulcercaseswhereImreallyconcerned,Iwanttouseapotentbroadspectrumantibioticinthefluoroquinoloneclass,saysDr.Sheppard.Ithinkthebest
fluoroquinoloneforulcersrightnowisbesifloxacin,becauseofitshighconcentration,itsabilitytoadheretothesurfaceanditssuperiorMICvaluesforawide
varietyofinfectiousbacterialorganisms,particularlymultidrugresistantstaphylococci.

Dr.Wittpennspreferreddrugforcornealulcersatthemomentisalsobesifloxacin.Ithasverygoodcoveragefromafluoroquinolonestandpointitcoversbot
grampositivesandgramnegativesanditcontainsbenzalkoniumchloride,heexplains.Certainfluoroquinoloneslikebesifloxacinorgatifloxacin,incombinatio
withBAK,remainveryeffectiveagainstmethicillinresistantbacteriasuchasMRSA,whichwereincreasinglyworriedabout.

Ifapatientcomesinwithanykindofulcerthatinvolvesanepithelialdefect,Iprescribebesifloxacineveryhourforthefirstday,hesays.Ifyoucantget
besifloxacin,mysecondchoicewouldbeafluoroquinolonewithBAKsuchasZymaxid.Ifthepatientsinsuranceisgenericonly,whichalotofplansouttherear
thethirdchoicewouldbeofloxacin,againbecauseithasBAKmixedin.Itsnotasgoodastheothertwo,butmayserveiftheotheroptionsarenotpossible.

Ifanulcerisadvanced,mostsurgeonssaytheydtreatwithmultipleantibiotics.Whentreatingamicrobialulcer,atypicaltreatmentistochoosetwoantibiotic
agentsandtreataggressively,saysDr.Foster.ByaggressivelyImeanperhapssixoreightinitialdrops,oneeveryfiveminutes,followedbyadropofoneof
antibioticseveryhouronthehourwithadropoftheotherantibioticeveryhouronthehalfhour.

Dr.Sheppardconcurs.Inmoreseverecases,Illusedualtherapywithbesifloxacinandgentamicin,hesays.Gentamicinisnotverysoluble,sowhilethe
besifloxacinachievesveryhighconcentrationsinitially,ittakesawhileforthegentamicintobuildup.However,gentamicinisavailableininjectablevials,sowh
thepatientisintheofficeIllgiveasubconjunctivalloadingdoseinjectionof0.3ccgentamicinmixedwith0.3cclidocaineatthetimeofpresentation,alongwith
dropofbesifloxacin.(Wedontneedtogivethisfluoroquinoloneeveryfiveminutestoloadthepatientbecauseofitssuperiorpharmacokinetics.)ThatwayIkn
thepatientisimmediatelyundertreatment.Hopefully,thepatientwillgotothepharmacyrightawayandpickuptherespectivedropsandthenreturntotheoff
inthatfirstcritical24hourperiod,soIcanseeifhesgettingbetter.
Dr.Fosternotesthattheressomedebateregardingwhetherornottousesocalledcompoundedfortified
antibiotics,typicallycompoundedinthehospitalpharmacy.Studieshaveindicatedthatthehourlyuseofabroad
spectrumfluoroquinolonesuchasgatifloxacinormoxifloxacinisjustasgoodas,forexample,fortifiedvancomycin
andtobramycin,hesays.
Dr.Johnpointsoutthatwhetherornottheepitheliumiscompromisedmakesadifferencewithregardtotopical
antibioticpenetrationintothecornealstroma.Iftheepitheliumisintact,topicalantibioticshaveahardtimegetting
intothecornea,hesays.Ontheotherhand,iftheulcerationhasalreadyremovedapieceoftheepitheliumand
partofthestroma,youdonthavetoworryabouttheepithelialbarrier.
Headdsthatwhentheepitheliumisintact,thelongeranantibioticstaysontheocularsurfacethemorelikelyitis
topenetrateintothecornea.Somedrugsincludeanadditionalcomponentthathelpsretainthedrugontheocular
surfacelonger,leadingtoincreasedcontacttime,hesays.Forexample,BesivancecontainsDuraSite
polycarbophil,edetatedisodiumdihydrateandsodiumchloride.

TheSteroidDilemma

Anecrotizingcornealulcercausedby
Pseudomonas.

Oneofthemostcontroversialissuessurroundingtreatmentofcornealulcersiswhenandwhethertotreatwithcorticosteroids.

Corticosteroidsareadoubleedgedsword,saysDr.John.Oncetheinfectioniscontrolled,steroidscanhelpdecreasethescarringthatcanresultfromthe
infectiousprocess.However,whentheresanactiveinfectionyoudontwanttousesteroidsbecausetheyllfrequentlyhaveadeleteriouseffect.Butthatisofte
milliondollarquestion:Howcanyoubecertainthecorneaissterile?

TheSCUTstudy(SteroidsforCornealUlcersTrial),alargeseriesinvolving500patientsthatwaspublishedintheArchivesofOphthalmology,foundnooverall
differenceinthreemonthBSCVAandnosafetyconcernswithadjunctivecorticosteroidtherapyforbacterialcornealulcers,hecontinues.ButIusuallyavoid
steroidswhenaninfectiousprocessisthere.IwouldonlyuseitwhenIbelievetheinfectioniscompletelyundercontrol,becauseyourecuttingdownthecorne
hostdefensesagainsttheenemyandtheycanhelptheorganismsproliferate.

Dr.Sheppardagreesthatcorticosteroidscanbeuseful,butonlyinspecificcircumstances.Ibelieveaclassicgrampositiveinfectionwillbenefitfrominitialster
therapy,hesays.RecentdatafromtheProctorFoundationtellsusthattheremaybeanimprovedvisualprognosisbutonlyforcentralulcerswhensteroids
prescribedinitiallyandthatthesteroidshavenosignificantunexpecteddeleteriouseffects[inthissituation].Ontheotherhand,ifthepatienthasafungal
infection,givingasteroidistheworstthingyoucando.Nopatientwithtraumashouldgetatopicalsteroidbecausetheriskofafungalinfectionismuchhigher.

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Dr.Fosterbelievesthatifyouresureamicrobeisbeingeffectivelytreatedwiththechosenantibiotic,ajudicioususeofsteroidtoreducepostinflammatory
responsedamagetothecorneaisperfectlyacceptable.Inthissituation,whereyouhaveasignificantlevelofcomfortthatyoureontopofthis,ifthereis
significantinflammationthatyoudliketoblunt,Ibelievemostcornealdiseaseexpertswouldagreethatsteppinginwithalittlebitofsteroidisreasonable,he
says.Imnotsayingitsstandardofcare,butitsreasonable.

Dr.Wittpenn,however,feelsthatsteroidsareneveragoodchoicewhentreatinganinfectiousulcer.Ifindthatsteroidswillgetyouintroublefasterthanthey
getyououtoftrouble,hesays.TheonlytimeIdusesteroidsisinacaselikeaphlyctenularkeratitis,whichisnotinfectious.Steroidshaveneverbeenshown
decreasescarring.Itstemptingtousethembecausetheyllhelpthepatientfeelbetter,atleasttransiently,andtheeyegetswhitefaster.However,steroidsca
maskalotofthings.

Onepatientwasreferredtomebecauseshegotascratchworkinginthegarden,hecontinues.Shewastreatedbyherlocaleyecareprovider,whothought
mightbebacterialandtreatedaccordinglyhowever,itnevergotcompletelybetter.Shestillhadsomeanteriorchamberreaction,andtheepitheliumdeveloped
funnyappearancewhereithadpartiallyhealed.Thedoctorthoughtthetraumamusthaveinducedaherpetickeratitis,soheaddedanantiviral.Buthestillsaw
inflammationintheanteriorchamber,sohealsoaddedasteroid.

Shewastreatedwiththesteroidandantiviralforaboutthreeweeksbeforeshewasfinallyreferredtomebecausetheulcerwasntgettingbetter,hesays.B
thenshehadstartedtodevelopafungalballinthedeepstroma,anditultimatelybrokethroughintotheanteriorchamber.Atthatpointwedidatapofthe
anteriorchamberandfoundthatshehadAspergillusniger.Itwasdifficulttotreat.Ittookmonths,including17intracameralinjectionsofanantifungal,
amphotericin,whichofcoursehadtobespeciallyprepared.Sheultimatelyneededatransplantandcataractsurgery.Inthelongrunshedidwellbutthestero
certainlymadethecasemuchmoredifficulttotreat.
SoItellcolleagues,ifyouredealingwithwhatyoubelieveisaninfectiousulcer,youhavetobeverycomfortablewithwhatyouredoingbeforeyouadda
steroid,heconcludes.ThatsprobablythenumberonemistakeIseecliniciansmake.

Dr.Johnnotesthatyoushouldalsorememberyourtreatmentpriorities.Steroidsmayhelptodecreasescarring,hesays,butifyouhaveabadcornealulcer
thenumberonepriorityistotrytogetridoftheoffendingorganismsandminimizetheoveralldirectandcollateraldamagetothecornea.Inthebestpossible
scenario,steroidsmightdecreasethesubsequentscarformation,butevenifyouusethemyoureoftennotgoingtoeliminatethescar.

FungalUlcers

Fungusissuggestedasthecauseofanulcerwhenthehistoryrevealsthattheulcerisnotbecomingrapidlyfulminant,Dr.Wittpennsays.Itsnotdeveloping
denseinfiltratequickly,anditsnotrespondingtoantibioticsthatarebeingusedappropriately.Anothercluethatfungusmaybeinvolvedisifthesourceofan
abrasionwasascratchfromvegetablemattersuchasbranchesorplants.AtleastuphereonLongIsland,thevastmajorityoffungalinfectionsItakecareof
havethathistoryitmaybealittledifferentinthesouthwherefungalinfectionsaremorecommon.

Fungalulcersareoftendiagnosedlate,becauseunlesstheresanobviouscausewegenerallybeginbyassumingthatpatientshaveabacterialkeratitis,notes
Sheppard.Fungalulcerstendtobecausedbytrauma,butifthepatienthasacompromisedsurface,lovesgardening,alreadyhadacornealtransplantorthere
foreignbodyintheeye,allbetsareoff.

Youhavetolookatthephysicalappearance,headds.Afungalulcertendstohaveveryfuzzymargins,tendstobedeeperandtendstopresentwithaplaqu
ontheendotheliumitmayhaveadelayedonset,andmayhavemultiplefoci.Thesecluescanhelpusdecidewhereweranktheprobabilityofafungalcausef
theulcer.

Dr.Wittpennsaysheusesseveralapproachestoaddressafungalulcer.Supposeapatientcomesinwithwhatappearstobeabacterialulcer,hesays.Its
beentreatedproperly,letssaywithtobramycineverytwohours,butitsnotgettingbetterorworse.ThefirstthingIddoisaddafortifiedvancomycinbecause
thetreatmentsofarhasntreallycoveredgrampositivebacteriathatwellIdalsoswitchthepatienttoafluoroquinolone.

AtthispointIdgivethepatienttwoorthreedaystoseeifheimproves,hesays.Thebestwaytodetermine
thatisbythereportedlevelofpaindropping,andbycheckingtheperipheralcornea,whichwillclearfirst.That
indicatethatyourenolongerrecruitingwhitecells,andthatsusuallyasignthatyouvefoundthecorrect
treatment.Youcantjudgebytheinfiltrate,becausetheinfiltratewillgetdenseratfirstitwillbegintohealast
whitecellsconsolidate.Iftheresnoimprovementontheantibioticsafterthreeorfourdays,Illhavethepatient
stopthedropsfor24hoursandthencultureforfungus.Occasionally,dependinghowbadtheulcerisandhowlo
itsbeenthere,Illbegintotreatwithanantifungallikenatamycinevenpendingthefungalcultures.

Aneurotrophickeratitiscausedbyalong
standingherpessimplexvirusinfection.This
eyeisatahighriskforsecondarybacterial
colonizationandinfection.

Dr.Johnnotesthatevenwhenthepatientshistorygivesyouahighindexofsuspicionthattheinfectionisfunga
youshouldtreatforpotentialbacterialinfectionattheoutset.Treatwithantibacterialsanddotheculturestopr
thatitisfungal,hesays.Antifungaltreatmentscanoftenbetoxictotheocularsurface.Inthisscenarioyoure
goingtotreatveryintensively,soyouwanttohaveadefinitivediagnosisbeforeyoustarttreatingwiththose
agentsalthoughofcoursetherecanbesomeexceptions,dependingontheclinicalsetting.Besides,eveniffun
ispresent,youcanalsohaveabacterialpresence.

Headdsthatitsalsoimportanttoknowwhatkindoffungusyouredealingwith.IsitCandidaorisitafilament
fungilikeFusarium?Thatalsocanhelpyoudecidewhattypeofantifungaltreatmenttoinitiate,hesays.Youcanchangeyourtreatmentdirectionoradd
antifungalagentsonceyouhaveadefinitivediagnosis,eitherbysmear,cultureorbiopsy.

MonitoringProgress

Onceyoustarttreatmentwithantibiotics,youhavetomonitorthecornealinfectionclosely,saysDr.John.Whenyoudocultures,yougetareportidentifying
organismandareporttellingyouwhethertheorganismissensitivetotheantibioticorresistant,butthesinglemostimportantfactoristheclinicalresponseto
treatment.Ifyouretreatingabadcornealulcerandyouseethattheinfiltratesizeisgettingsmaller,theulcerationisnotgettingworseandthereisevidenceo
healingtakingplace,especiallyintheperiphery,thenofcourseyouwanttocontinuewiththesametreatmentmodality.Ontheotherhand,ifyouretreating
aggressivelywithanantibioticandtheulcerisgettingworse,youhavetochangedirectionoraddadditionalantibiotics.

Dr.Johnpointsoutthatbacterialorganismsareveryadaptable.Theybecomeresistanttoantibiotics,hesays.Itsaconstantbattletokeepaheadofthem.S
youhavetomonitorverycloselytoseeifyourocularantibioticchoicesareworkingfromaclinicalstandpoint.

Ifmedicaltreatmentfailstowork,surgerymaybecomenecessary.Youdontwanttowaittoolongforsurgicalinterventionwhenthereisanexpandingulcerw
medicaltherapeuticfailure,notesDr.John,addingthattheclinicalresponseisdependentpartlyuponthelocationoftheulcer.Forinstance,ifyouhavea
Pseudomonasulcerthatisparacentralandisexpandingrapidlydespitemedicaltreatmentandmovingtowardsthelimbus,youmayhavetoconsidersurgical
interventionsuchasatherapeutickeratoplasty.Ifthatinfectionspreadsfromthecorneatothesclera,resultinginPseudomonasaeruginosakeratoscleritis,then
theoddsofsavingtheeyeasawholecanrapidlydiminish.Evenincaseswhereeviscerationorenucleationarenotnecessary,thevisualprognosisusually
remainspoor.

Ontheotherhand,ifthetreatmentisworking,theclinicianhastodecidewhentotaperthemedications.Iftheinfiltrateisdecreasing,thepainisdecreasing,th
rednessisdecreasingandtheepithelialdefectisimproving,thenIknowthatthepatientisrespondingtotherapy,saysDr.Sheppard.Onceallofthesymptom
aregoneandtheepitheliumiscompletelyresurfaced,Ifeelsafeinconcludingthatweveeliminatedthebacteria,andwecanbegintorapidlyweanthepatient
theantimicrobialtherapy.Sometimes,becauseofthetoxicitythatcomeswithanypotentantibioticgivenfrequently,wecutbackonthedosagefrequencyonce
seeimprovementassumingthattheinformationfromtheculturesalsoindicatedthatthecurrenttherapeuticregimenistherightone.Finally,wewatchthe
patientforaboutaweekafterwestoptheantibioticstomakesurethecornearemainsclearwithouttherapy.

ClinicalPearls
Thesestrategiescanhelpyouavoidcommonmistakesthatmightundercuttheeffectivenessofyourtreatment:

Dontconfuseaninfiltratewithanulcer.Dr.Fosternotesthataninfiltrate,byitself,isnotsynonymouswithacornealulcer.Acornealinfiltrateindica

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thatsomewhitebloodcellshavemigratedintothecornealstroma,butthatdoesntmeananulcerispresent,heexplains.Inatrueulcer,theresalossoftiss
withstromadigestedbyenzymes.Theresultisadivot,justlikeanulcerintheliningofthestomach.Aninfiltrateisofconcernbecauseitcaneventuateintolos
tissuehence,anulcerbutitsimportanttomakethedistinction.

Ifyouhaveaperipheralinfiltrateinacontactlenswearer,withnolossofstroma,norealulcerationandanintactepithelium,stopthecontactlensuse,usea
topicalcombinationofantibioticandsteroidandseethepatientfrequently,hecontinues.Idseethepatientthenextday,andifhelooksgood,seehimtwoda
later,thenfourdayslater,andsoforth.

Bewareofundertreatingacontactlensrelatedulcer.Sometimesacontactlenspatientcomesinsoearlythatyoudontevenseeabiginfiltrate,
notesDr.Wittpenn.Ialwayswarnpeopleaboutapatientwhosays,IthinkIscratchedmyeyewhenItookoutmycontactlenslastnight,becauseIwokeup
thismorninganditwasrealsoreandbotheringme.Allyouseeisacornealdefectnoinfiltrate.Inthissituationyouneedtobealertforanycellsintheanteri
chamberandanykindofhazeatall.

Myadvicetomostcliniciansis:Anycornealdefectinthesettingofcontactlensuseisacornealulceruntilprovenotherwise,hecontinues.Thebiggesterror
cliniciansmakeinthissituationisprescribinganantibiotictwiceorfourtimesaday.Whenyouhittheulcerwithalowdoselikethatparticularlyifyoureusing
oneoftheverypopularantibioticsliketobramycinorgentamicintreatmentmightbeeffective,butthosedrugshavegapsintheircoverage.Threedayslatert
areastillisntreallyhealedinitsmoreinflamed,andnowyourenotsureifyouredealingwithanunusualfungalulcerorsomethingelse.Doctorsendupsend
thesepatientstometoruleoutfungus,wheninfactitsanundertreatedbacterialulcerthatjustneedstobehithardwithtopicalantibiotics.

Acentralcontactlensassociatedulcercanhavedevastatingeffectsonvision,anddevelopveryquickly,within24hours,headds.Thatswhyanyproblem
associatedwithacontactlensshouldbetreatedaggressively.Ifitreallyisnothingbutadefect,nothingislost.Ifitsthestartofaninfection,youmaysavethe
patientsvision.

Whenchoosinganantibiotic,alwaysconsideravoidingthosethepatientmayhaveusedpreviously.Ifthepatienthashadaparticular
antibioticsuchasazithromycinorOcufloxinthepastbecauseofcataractsurgeryoraboutofconjunctivitis,youmaynotwanttotreattheulcerwiththose
medicationsparticularlyifthepatientmayhaveabusedthembynotusingthemforthefullcourseoftherapy,observesDr.Sheppard.Instead,iftheulceris
serious,pickaverypotent,broadspectrumantibiotic,especiallyifyoureselectingmonotherapy.Ifyoureusingmultipledrugs,selectastrategythatwillcover
thebroadestrangeofpotentialpathogens.

Bealertforashieldulcer.Oneformofulcerthatsbeenalittlemoreprevalentrecentlyisashieldulcer,whichisassociatedwithsevereallergic
conjunctivitis,commonlyseeninteenagemales,thoughitcanalsobeseeninyoungadultmales,saysDr.Wittpenn.Theygetsuchasevereallergicreaction
inflammationundertheirupperlidsthattheepitheliumofthecorneabreaksdowninresponsetotheinflammatorypapillaethatform,whichbecomebigbumps
cancauseanulcer.Therealproblemoccursifthatulcerbecomessecondarilyinfected.
Patientsinthissituationneedtobemanaged
carefully,hecontinues.Theyoftenneedtobe
treatedwithatopicalsteroidinconjunctionwith
anantibiotic.Unlessyourecomfortablehandling
thistypeofulcerbecauseyouvetakencareofa
lotofthem,youreallyshouldsendthispatientto
aspecialist.Thesepatientscangetintotrouble
quickly,particularlyiftheygetaninfectiousulcer
centrallysuddenlyyouredealingwithabadscar
andapatientwhomightbefairlyyoungbutneeds
acornealtransplant.
Warnpatientsaboutsecondaryfungal
infections.Manytimesyoutreatabacterial
infectionwithantibioticsandthebacterialinfection
getsbetter,saysDr.Sheppard.Thenthepatient
isrunningaroundinthegardenorworkinginthe
basementoratticorplayingwithapetandgetsa
fungusintheeye.Funguswillgrowmorerapidly
inaneyewithantibioticsonboard,because
suppressingthebacterialgrowthallowsfungito
growfaster.Asaresult,weveoftenseen
secondaryfungalinfections.Itsworthmentioning
thistothepatient.

MakeSureYourStaffIsPrepared
Inthestruggletopreservevisioninthefaceofacornealulcer,yourstaffarethefirstlineof
defensetheiractionscanmakeorbreakapositiveoutcome.
Makesurestaffmembersknowwhenacallmightbeaboutadevelopingcorneal
ulcer.Itsoftenastaffmemberwhofieldsapatientinquiryrelatedtoacornealulcer,nottheeyecare
provider.TheOMICmalpracticeinsurancecompanystatesthatthethirdleadingcauseofmalpractice
lawsuitsagainstophthalmologistsistriagebystaffmembers,saysJohnSheppard,MD,MMSc,
professorofophthalmology,microbiologyandmolecularbiologyatEasternVirginiaMedicalSchoolin
Norfolk,Va.Thismeansthattriagepersonnelhavetobereallytunedintowhichphonecallsare
importantandwhatconstitutesapotentiallyblindingcondition.
Inalargepercentageofthesephonecalls,itsredeyethatwereconcernedabout,henotes.If
theredeyeisoflongduration,withnoriskfactors,nopainorpurulentdischargeorlossofvision,
thatsonethingthatsquitecommon.Butwheneverthepatientscommentsindicateariskfactorfor
bacterialkeratitis,suchaspainandphotophobiainadditiontotheredeye,especiallyinconjunction
withcontactlenswearortrauma,thetriagepersonhastogetthepatientintotheofficerightaway.
Thelastthingyouwanttodoisdelaythepresentationofanulcer.
Tellyourstaff:Ifapatientmighthaveanulcer,dontputdropsinhiseyes.Asidefrom
dilutingtheflora,mostoftheeyedropsweusetoreducepain,checkIOPordilatethepupilscontaina
preservative,explainsDr.Sheppard.Thepreservativemaysignificantlyreduceourchanceofculturing
anorganismfromtheeye,whichultimatelyguidesourtherapyparticularlyindifficultcases.Eventually
wellusepreservativefreetetracainetocultureanddebridethecornea.
Makesureyourstaffknowsthatredeyemightalsoindicateadenovirus
keratoconjunctivitis.Thesepatientscanhavesymptomssimilartothoseofanulcer,buttheyre
extremelycontagious,notesDr.Sheppard.Fortunately,theAdenoPluspathogenscreenerfromRPS,
distributedbyNiCox,allowsustoconfirmwhetherornotapatienthasthisconditionwithinaboutfive
minutes,withveryhighsensitivityandspecificity.

Tellcontactlenspatientsthattheyneed
tohaveapairofspectaclesinreserve.
Contactlenswearersoftenrejectthisidea,
notesDr.Wittpenn.Theysay,Iwearmylenses

allthetime.Itellthemthattheyhaveto
understandthatifacontactlensstartstobother
them,theyhavetobeabletoremoveitandwearglassesuntiltheproblemisresolved.Iveseenpeoplegetthemselvesintroublebecausetheyhadnospectac
tofallbackon.

Becarefulaboutdiagnosinganinfectionasbeingherpesbased.Itspossibletomisdiagnoseaninfectionasaherpesinfection,leadingtotreatme
usingantiviralagents,saysDr.John.Infact,thatearlydendritelikelesionthatyouseemaybearadialkeratoneuritisoranearlyepithelialridgelikelesion
secondarytoAcanthamoebakeratitis.ThatmisdiagnosiscoulddelaythetreatmentofAcanthamoebaandhaveadeleteriouseffectonthepatientsvision.

Dontbeafraidtohospitalizeapatient.Youhavetoconsiderthepossibilitythatcomplianceisanissue,especiallyiftheulcerisgettingworseinspite
yourhavingprescribedwhatyouthinkisthestateofthearttreatmentforthegivenproblem,saysDr.John.Puttingthepatientinthehospitalmaybeagood
alternativeifthepatientisnoncompliant,becausetimeisoftheessence,especiallyifyouredealingwithanorganismlikePseudomonas.Youcantellthepatien
thathewontbeinthehospitalfortoolonghellbedischargedassoonastheulcerbeginstogetbetterandhecanmanagethetreatmentathome.

Dr.Fosteragrees.Ifthepatienthasamicrobialulcerationthatneedsaggressivetreatment,inmyexperiencethevastmajorityofpatientscannotbetrustedto
getitdone,hesays.Byfarthebestsolutionistoletthenursesdoit.Putthepatientinthehospital.Noinsurancecompanywouldeverargueabouthospitalizi
apatientforaninfectiouscornealulcer.Headdsthatthisisespeciallyimportantiftheulceriscentralorparacentral.

Dontassumethatongoingcornealopacitymeansyourtreatmentisntworking.Dr.Johnnotesthatcliniciansmaybefooledintoovertreatingb
anongoingcornealopacity.Atreatedulcermaybeundercontrol,buttheclinicianisconcernedabouttheongoingcornealopacity,heexplains.Thisopacitym
betheresultofthescarringprocessratherthantheinfection,butthecliniciankeepstreating.Thiscanleadtosurfaceissuessuchastoxicityfromthedrugsand
cornealsurfacebreakdown.Theclinicianshouldbetaperingthemedicationbecausetheinfectiousprocessisundercontrol.
Signsthatyourtreatmentisworkingdespitetheopacityinclude:healedcornealepitheliumthatwasinitiallybrokendowndecreasingcornealstromaedema
surroundingtheareaofinitialdenseinfiltrateandblurryinfiltratemarginsbecomingmoredistinct,headds.

Considerusingcyanoacrylategluetoforestallaperforation.Aperforationisaprettyscaryevent,notesDr.Sheppard.Wemayputcyanoacrylat
glueonacorneathatsthinning,andasmallperforationcanbeglued.Alargeperforation,unfortunately,isgoingtorequireanemergencytransplant.

WhenShouldYouRefer?

Anytimeyouredealingwithatypeofulceryouseldomtreat,suchasashieldulcer,youshouldconsiderreferringthepatient,saysDr.Wittpenn.Generally,
youhavetobeverycomfortablediscerningwhetheranulcerisinfectiousornoninfectious.Also,anyulcerthatisntdoingwhatyouexpectittodoshouldbe
referred.Clinicianshaveatendencytosay,Wellthisisntterrible,butitisntgettingbetter.MaybeifIjustgiveitalittlesteroidWheneveryougettheurge

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ReviewofOphthalmology>WinningtheBattleAgainstCornealUlcers
reachforasteroidbecauseyouthinkitwillhelptheeyehealfaster,Iurgeyoutoresist.Thatsthemainchoicethatgetscliniciansintotrouble.

Ifyoudontactuallyenjoymanagingthesekindsofcases,donttrytomanagethem,addsDr.Foster.Justreferthecaseouttosomeonewhodoesenjoythi
typeofcase,ortothelocalresidencyprogram.REVIEW

Dr.JohnisaconsultantandspeakerforBausch+Lomb.Dr.WittpennhasbeenonthespeakersbureauatB+LandAllerganandhasreceivedresearchsuppor
fromAllergan.Dr.SheppardisaconsultantforRPS,NiCox,Alcon,Merck,AllerganandB+L.

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