Herpes Simplex Keratitis By Jeremy Lemmons
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1 Journal of Ophthalmic Medical Technology HerpesSimplexKeratitis ByJeremyLemmons Volume 7, Number 1 September History Ocularherpesisusuallycausedbythesamevirusresponsibleforcoldsoresonthelip,herpessimplex virustypei.herpessimplexvirus(hsv)typicallyaffectsonlyoneeyeandisnotasexuallytransmitted disease.itisspreadbycontactwithpeoplewhohavethevirus.around50,000peopledevelopocular herpesintheunitedstateseachyear.likeotherherpesinfections,ocularherpescanliedormantfor manyyearsinthe5 th cranialnerve,ortrigeminalnerve,andthenrecur.theexactcauseofanoutbreak isunknown,butstressbroughtonbyfever,sunburn,majordentalorsurgicalproceduresandtrauma areoftenassociatedwithincidents.accordingtothenationaleyeinstitute,oncetheinitialoutbreak occursthereisa40to50percentchanceofherpesreturning.althoughsymptomsusuallypresent themselvesinoneeye,theviruscouldaffecttheothereyeaswell.amongpatientswithocularhsv, thosewithpreviousstromalinvolvementhaveasignificantlyhigherriskofsubsequentstromal keratitis;incontrast,patientswithepithelialkeratitisalonehavenoincreasedrateofrecurrenthsv disease.symptomsofthediseaseincludepain,photophobia,blurredvision,tearingandredness. Examination A37yearoldblackfemalepresentstocliniconemonthearlierwithcomplaintsofdiscomfort, photophobia,andrednesstoherlefteye.shesaidshehashadahistoryofherpesinherlefteyesince earlychildhood.shealsohasbeenonviroptic inthepastandaswellassteroids.shehadnoevidence ofanydendriticchangeonthesurfaceofthecornea,butdidhavestromaledemaandsomekeratic precipitates.herintraocularpressurewas14mmhginthelefteyeandwasnotcheckedintheright. Shewasthoughttohaveadisciformherpeticlesionwithoutevidenceofanyactivevirusatthispoint. ShewasputonPredForte,Atropine,andViroptic.Thepatientwastoldtoreturninthreedaysbutdid notreturnforonemonth.onreturn,thepatientstatedthatshehadnotcontinuedonthemedications asdirectedforthepastfewweeks.herlefteyewasredandhadadendriticlesion.thethree medicationswererestartedandshewasreferredtoacornealspecialistforapossiblecorneal transplant. Thepatientwasseentwoweekslaterbythecornealspecialist.Uponexamination,hervisualacuitywas 20/25intherighteyeand20/200intheleftwithapinholeto20/80.Herpupilexamshoweda pharmacologicallydilatedleftpupil.extraocularmotilitywaswithinnormallimits.intraocularpressure was18intherighteyeand13intheleft.slitlampexaminationshowednormallidsandocularadnexa. Examinationoftherightcorneashowedsomemoderatecornealguttae.Theleftcorneashowed cornealguttaeandendothelialpigmentationwithcentralstromalhazediffuselyinvolvingthevisualaxis. Theanteriorvitreouswasquiet.ThepatientwasfoundtohaveHSVkeratitisOS,Fuch sdystrophyod, andamblyopiaosduetoaremotehistoryofeyeinjuryatagetwo.theplanwastodiscontinuethe
2 ViropticandrestartthePredFortetwicedaily.ThepatientwasalsoputonAcyclovir400mgorallyfive timesaday.thepatientwasnotacandidateforatransplantuntilfreefromactivediseaseforoneyear. Thepatientreturnedtoclinic6weekslaterwithcomplaintsofacutepaininthelefteyeandstatedthat hervisionwasworse.shealsosaidshewashavingalotofdrainage(yellow)inthelefteyeandfelta throbbingsensationbehindit.patientsaidshediscontinuedthesteroiddropsoneweekago.hervision was20/25intherighteyeand20/200intheleftwithapinholeto20/70.intraocularpressurewas17in therighteyeandtheywereunabletogetareadingintheleft.theassessmentshowedageographic scar/epithelialdefectanduveitisos.theplanwastocontinueacyclovirandaddviropticthreetimesa dayanderythromycinfourtimesaday.thepatientwastoldtoreturntoclinicinoneweekbutwaslost tofollowupuntilthreeandahalfyearslater. Patientreturnedtoclinicwithcomplaintsofpaininthelefteye.Shewasnottakinganymedications. Hervisionwas20/20intherighteyeand20/200intheleftwithapinholeto20/60.Theimpressionwas stillthesameasthreeyearsprior.shewasputonacyclovir400mgfivetimesdaily,predforteevery twohoursinthelefteye,cyclogelthreetimesdailyinthelefteyeandshewastoldtoreturntoclinicin 1week.Patientreturnedtoclinicandthekeratitishadimproved.ShewastoldtotaperoffofthePred Forteandcontinuetherestofthemedicationsinadditiontoerythromycinointmenteverynightat bedtime.thepatientwastoldtoreturntoclinicintwoweeks.shereturnedwithimprovedsymptoms butthedendritehadworsened.shewastoldtodiscontinuethepredforteandcyclogyl,beginthe Acyclovirfivetimesdaily,andreturntoclinicinsixdays.Thepatientreturnedtoclinicinthreedays withseverepaininthelefteyewhenpredforteandcyclogylwasrestarted.shewastoldtoreturnto clinicinthreeweeks.thepatientwaslosttofollowupagain. Discussion HSVkeratitismaybedividedinto4categories:infectiousepithelialkeratitis,neurotrophickeratopathy, stromalkeratitis,andendotheliitis.thefirstoneisinfectiousepithelialkeratitis.themostcommon signsassociatedwiththisformaredendriticulcers,cornealvesicles,andgeographiculcers.thefirst signsthatsuggestingthereisactivevirusareraisedvesiclesonthecornealepitheliumthatmimicthe mucocutaneousherpesseenelsewhereinthebody.ifapatienthasbeenknowntohavehsvkeratitisin thepasttheymaypresentwiththesevesiclesandbeasymptomatic.thosepatientsthatdonothavea priorhistorymaynotpresentwiththesesignsontheirfirstvisit.thenextsignthatmaybeseenisa dendriticpatternonthecorneaformedbytheraisedvesicles.thiswillhappenwithinseveralhoursof theinitialappearanceofthevesicles.inimmunocompromisedpatients,therecurringinfectionmaybe seenatthevesiclestage,buttypicallytheinfectionisnotcaughtthisquickly.themostcommon presentationofhsvkeratitisisthedendriticulcerthatresultsfromthecentralepithelialdefect. Branchingterminalbulbs,swollenepithelialborders,andcentralulcerationthroughthebasement membranearethesignsthatmakeupthedendriticulcer.oncethisdendriticulcerprogressesand becomelarger,itisreferredtoasageographiculcer.
3 PhotocourtesyofJonesEyeInstitute Dendriticulcerseenininfectiousepithelialkeratitis ThenexttypeofHSVkeratitisisneurotrophickeratopathywhichdevelopsinpatientswithpreviousHSV epithelialdisease.thistypeofthediseasearisesfromdefectedcornealinnervationsanddecreasedtear formation.itcanbecausedbylong termuseoftopicalmedicationsuchasantiviralagents,butitisalso thoughtthatviralreplicationcanbemorecommoninepithelialdefectsthatcomebackfrequently.the earliestsignsforthistypeofhsvareanirregularcornealsurfaceandpeeorpunctuateepithelial erosions.ifthesepeeprogresstheycanleadtostromalulceration.typically,aneutrophiculcerisoval inshapeandhassmoothbordersunlikethescallopedbordersofageographiculcer.also,thereis decreasedcornealsensationwithneutrophiculcers.neovascularization,necrosis,andperforationare somecomplicationsofneurotophickeratopathy. ThethirdformofHSVkeratitisisstromalkeratitis.Thetwoformsofthisdiseasearenecrotizingstromal keratitisandimmunestromalkeratitis.itcanbesecondarytoinfectiousepithelialkeratitis, neurotrophickeratopathy,orendotheliitis.stromalinflammationcouldalsobetheprimary manifestation.densestromalinfiltrate,ulceration,andnecrosisarethemostcommoncharacteristicsof necrotizingstromalkeratitis.thisisthoughttoresultfromviralreplicationinthestromalkeratocytes andaninflammatoryresponsefromthehost.thisinflammationmayleadtothinningandperforation withinashorttimeperiod.theuseoftopicalcorticosteroidsmaybeariskfactorfordevelopmentof necrotizingstromalkeratitis.immunestromalkeratitis(isk)iscommoninrecurrenthsvkeratitis.the causeisbelievedtobeanantibody complementtoviralantigenswithinthestroma.cellularinfiltrates, neovascularization,immunerings,orghostvesselsaredescriptiveofiskduringclinicalpresentation. Alsoaccompanyingstromalkeratitismaybeanteriorchamberinflammationandstromalscarringwhich canleadtoprofoundvisualloss.stromalkeratitispatientscanalsodevelopuveitis,trabeculitis,and secondaryglaucoma. PhotocourtesyofJonesEyeInstitute Patientwithstromalkeratitis
4 ThefinaltypeofHSVkeratitistobediscussedisendotheliitis.Thesignsincludekeraticprecipitatesor KP,absenceofanystromalinfiltrateorneovascularization,andstromalorepithelialedema;commonly iritiswillbeassociated.thethreetypesofendotheliitisaredisciform,diffuse,andlinear.ifitis disciformtherewillbearoundareaofcornealedemainthecentralregionofthecornea.diffusecan formfromapreviousdisciformareaandshowskpthatisscattered.linearendotheliitisshows peripheralcornealedemaandeitherasectoralorstraightlineofkpthatmovescentrallyfromthe limbus.thecauseofendotheliitisisthoughttobeanimmunologicreactiontoviralantigensinthe cornealendothelialcells,butactiveviralreplicationmayalsohavesomethingtodowithit.the endothelialinflammationmaycausedecompensationwhichcanleadtostromalandepithelialedema. Causes PhotocourtesyofJonesEyeInstitute Patientwithdisciformendotheliitis ThecausesofHSVkeratitisvarywiththedifferenttypesofdisease.Infectiousepithelialkeratitisresults fromviralreplicationwithinthecornealepithelium.neurotrophickeratopathycouldbecausedby manythingsandisnotwellunderstood.somethinkitcouldbecausedbyuseoftopicalagents,stromal inflammation,aswellaspoorcornealinnervationsandtearsecreation.ithasalsobeenshownthat activehsvreplicationcanbepartofthecause.necrotizingstromalkeratitisiscausedbyhost inflammatoryresponsethatistriggeredbyinfectionofthecornealstroma.immunestromalkeratitisis believedtobecausedbyanantibody complementthatisactivatedbyviralantigenswithinthestroma. Finally,endotheliitisisthoughttobecausedbyanimmunologicreactiontoanantigenintheendothelial cells,althoughanactivevirusisalsosuspectedtoplayarole. Treatment/Post treatment Treatmentforocularherpesdependsonwheretheinfectionislocatedintheeye inthecorneal epithelium,cornealstroma,irisorretina.ifthecornealinfectionislimitedtothesuperficiallayers,it cannormallybealleviatedbyusingantiviraleyedropsorointments,ororalantivirals.zirgan was approvedbythefdainlate2009asatopicalantiviraltreatmentforeyeherpes.cornealscrapingscan sometimesreducetheviralloadandspeedthehealings.thetreatment(ganciclovirophthalmicgel, 0.15percent),whichbecamecommerciallyavailableintheUnitedStatesinlateApril2010,involves instillingeyedropsfivetimesdailyuntiltherelatedcornealulcerheals.steroiddropscanalsohelp decreaseinflammationandpreventcornealscarringwhentheinfectionappearsdeeperinthecorneal layers.steroiddropsarealmostalwaysusedinconjunctionwithandsimultaneouslywithantiviraldrops. Steroiddropshavebeenknowntocauserecurrenteyeherpesinfectioninsusceptiblepatientsbecause theydecreasetheeffectivenessoftheeye simmunesystem.also,anantibioticeyedropalongwitha
5 therapeuticcontactlensmaybeusedtopreventasecondarybacterialinfectionwhiletheherpeseye infectionisbeingtreated. Aneyedoctormaytreateyeherpesbyscrapingawaytheinfectedcornealepithelialcellswithacotton swaborcorneal"spatula"instrument.thisiscalleddebridement.followingdebridement,apatchor softcontactlensmightbeneededtohelpthecorneaheal.incaseswherecornealscarringis permanent,acornealtransplantmayrestorevision. Conclusion Rangingfromasimpleinfectiontoablindingcondition,thereareseveralformsofocularherpes. Tearing,eyeredness,blurryvision,andoculardiscomfortarethemostcommonsymptoms.Since cornealanesthesiacanoccurinthecourseoftheinfection,thepatientcanalsobeasymptomatic. Althougheyeherpeshasnocure,treatmentcanhelpcontroloutbreaks.Studiesareunderwayto determinebettermethodsformanagingthedisease. References HerpeticEyeDiseaseStudy(HEDS)I bythenationaleyeinstitute. Vaughan&Asbury sclinicalophthalmologybypaulriordan EvaandJohnP.Whitcher.Pages , ,324.McGraw Hill2008. DiseasesoftheCorneabyMerrillGrayson.Pages TheC.V.MosbyCompany1979. Duane sclinicalophthalmologybywilliamtasmanandedwarda.jaeger.volume4,chapter19. LippincottWilliamsandWilkins1998(revised).
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