Differenteffectsofcornealcrosslinkingoninfectiouskeratitis 窑Review窑 Therapeuticandinducingeffectofcornealcrosslinking oninfectiouskeratitis 1DepartmentofOphthalmology,ShandongProvincial thecornealintrinsicbiomechanicalpropertyandthestiffness HospitalAffiliatedtoShandongUniversity,Jinan250000, ofcorneatoresistectasiaofcornea [1].Besidesitsoriginal ShandongProvince,China applicationforthekeratoconusandkeratectasia [2],CXLhas 2DepartmentofOphthalmology,thePeople'sHospitalof beenutilizedontothetreatmentofinfectiouskeratitis [3], Linyi,Linyi276000,ShandongProvince,China nowadays.Althoughthesecondaryinfectiouskeratitisafter 3DepartmentofPediatrics,thePeople'sHospitalofLinyi, CXLisrare,therearesomereportsonsecondarykeratitis Linyi276000,ShandongProvince,China infectedby bacteria,fungi,herpessimplexvirusand Co-firstauthors: Liang-ZhuJiangandShi-YanQiu Acanthamoeba.ThisrarecomplicationofCXLcancause Correspondence to: Guo-YingMu.Departmentof seriousocularmorbidityandhaveasubsequentdamaging Ophthalmology,ShandongProvincialHospitalAffiliatedto effectonthepatient'svision.ThesurgicaltechniqueofCXL ShandongUniversity,Jinan250000,ShandongProvince, involvestheremovalofepitheliumintraoperativelyandthe [email protected] applicationofcontactlenspostoperatively.Thesefactors Received:2015-06-30Accepted:2016-08-09 havebeenassociatedwiththeoccurrenceofinfectious keratitisafterCXL.Inpresentstudy,wesummarizedthe Abstract therapeuticeffectofCXLoninfectiouskeratitisandthe · Thecornealcrosslinking (CXL)withriboflavinand keratitissecondarytocorneaCXLreportedbyprevious ultraviolet-A (UVA) isanew therapymethod to studies,andprovidedouropiniononthetherapeuticand successfullytreatinfectiouskeratitisinclinicalpractice. inducingeffectofCXLonkeratitis. However,therearerarereportsonthecomplicationsof TREATMENT OF KERATITIS WITH CORNEAL CXLsuchasthesecondarykeratitis.Thediverseclinical CROSSLINKING outcomesonkeratitishavehighlightedthenecessityto StudiesofCornealCrosslinkingonKeratitis furtherevaluatetheefficacyandcomplicationsofCXL. LaboratorystudieshaverevealedthatUVAirradiation WereviewedthepositiveandnegativereportsonUVA/ combinedwithriboflavinsolutionadministrationeradicates riboflavinrelatedwithkeratitisandprovidedouropinion orinhibitsthegrowthofbacteria [4],Staphylococcusaureus, onthetherapeuticandsideeffectofUVA/riboflavin Pseudomonasaeruginosaor[5] andFusariumsolani[6],however, crosslinkingonkeratitis. anegativeanti-microbialeffectofCXLwasreportedby · KEYWORDS: cornealcrosslinking;keratitis;theraputic otherstudiesonCandidaalbicans [4,7],Acanthamoeba [8-9],and andinducingeffect Fusariumsolani [7].Beforecrosslinkingtreatment,patients DOI:10.18240/ijo.2016.12.20 oftenreceiveantibioticandsteroidtreatment,anditis difficulttoisolatetheactionofthecrosslinkingwithother JiangLZ,QiuSY,LiZW,ZhangX,TaoXC,MuGY.Therapeuticand treatments.Itispossiblethatthecombinationoftreatments inducingeffectofcornealcrosslinkingoninfectiouskeratitis. andthesignificantlysmallernumberofcystsand 2016;9(12):1820-1823 trophozoitesinthecorneaduringtheinfectionallowedthe INTRODUCTION eradicationoftheamoeba.Themostlyusedirradiation nfectiouskeratitisisacommonlyencountereddiseasein patterninpreviousstudiesis30minexposuretoUVAwith 2 I clinicalpractice.Routineanti-microbialtreatmentsare energydensity3mW/cm .Theanti-microbialeffectofUVA oftenlesseffectiveinsomeseverecasesespeciallyin seems inanexposure-durationdependentpattern,as keratitiswithfungiornon-responsivebacterial.Corneal Makdoumi [10] revealedthatthe60minexposureof crosslinking(CXL)wasfirstlyintroducedintothetreatment bacterialsuspensiontoUVAeradicatesthemicroorganismin ofkeratoconusin2003byWollensak [1].Thebasic solution,while30minexposurehaslimitedeffectof principleisthattheexposureofcorneasaturatedwith eradication. riboflavintoUVAwithawavelengthof370nmandenergy ClinicalStudiesofCornealCrosslinkingonKeratitis densityof3mW/cm2,itinducesadditionalcovalentbindings Clinically,CXLhasbeendescribedeffectiveintreating betweenamino/groupsofcollagenfibersandaimstoenhance keratitiscaseswithEscherichiacoli [11],Acanthamoeba [12-14], 1820 陨灶贼允韵责澡贼澡葬造皂燥造熏灾燥造援 9熏晕燥援 12熏 Dec.18, 圆园16 www.ijo.cn 栽藻造押8629原愿圆圆源缘员苑圆 8629-82210956 耘皂葬蚤造押ijopress岳员远猿援糟燥皂 Pseudomonasaeruginosa [15],Staphylococcusaureus, polymicrobialkeratitiscausedbySepidermidis [31], Aspergillus [16-17],Fusarium [17],othertypesofbacteria [18],and Staphylococcusaureus.andMethi-cillinResistant herpesvirus [18].Howerver,somereportsalsorevealedthat Staphylococcusaureus(MRSA) [32],Streptococcussalivarius CXLcaneffectivelytreatinfectiouskeratitisbutexcluding andS.oralis [33] hadbeenreported.Secondarykeratitisafter viralkeratitis[19].Chan [20] alsoreportedtheroleofCXL corneascrapings hasalsobeenreportedrecently [34]. ininfectiouskeratitisremaineduncleardespitethereported Fortunately,followingtreatment,theulcerdecreasedinsize, successinsomeclinicalcases,Kymionis [21] reported onlyleavingacornealscar.2)Fusariumkeratitis3wkafter cornealmeltingresolvedafterCXLtreating.Uddaraju [22] healedCXLhasbeenreportedin2010 [35].Cornealscrapings reportedCXLusedasadjuvanttherapyforrecalcitrantdeep revealedfungalhyphae,whichwerelateridentifiedas stromalfungalkeratitis,however,ofthe13casesenrolledin Fusariumsolani.Thepatientsweretreatedwithtopical thestudy,fiveeyesintheCXLgroup(6eyes)and3eyesin amphotericinBandvoriconazolefor2mo.Theoutcomes thenon-CXLgroup(7eyes)experiencedtreatmentfailure.In revealedFusariumspeciescouldcauseinfectiouscrystalline asecondaryanalysis,theCXLgroupexperiencedmore keratopathyafterCXL treatment. 3) Dendriticand perforationsthanthenon-CXLgroup(4 0) [22-23].CXL geographicalherpessimplexkeratitiswithorwithoutiritis [36-37] treatmentwassimultaneouslycombinedwithsomesurgical afterCXLhasbeenreported .Thepatientshadnohistory proceduresincludingkeratoplasty [24],amnioticmembrane ofherpetickeratitis.Thediagnosisofherpessimplexvirus transplantation [25],conjunctivalflapcovering [21], .The (HSV)wasconfirmedwithpolymerasechainreaction(PCR) exposuredurationofUVAduringCXLtreatmentranged tearanalysis.Itwasreportedemotionalstress,trauma,fever, [38] from5to45min,aswellasavariationofriboflavin andlasersurgerycouldtriggerHSV .TheUV-Ainduced concentration.Whilethetotalenergy ismaintained, thereactivationofalatentHSVinfectionintheprocessof CXL [19].Themechanismcouldbethetraumaofcorneal accordingtotheBunsen-Roscoephotochemicallawof epithelialandstromalorthedamageofcornealnerves.4) reciprocity,theeffectsofphotochemicalreactionaresimilar Acanthamoebakeratitisassociatedwithcornealmelting5d evenifthetimeandintensitychange [3].Theassessedclinical afterCXLhasbeenreported.Thepatientwashedeyewith outcomesincludethehealingofcornealulcer,thestoppingof tapwaterseveraltimesbecauseofignoringthebandage theprogressionofcornealmelting,andthedisappearingof contactlensbeinginserted [39].Therapidprogressionof cornealedema, .Todate,mostclinicalstudieswere cornealmeltingledtothecornealperforation,sothe performedinaretrospectiveandsmallscalepattern. therapeuticpenetratingkeratoplasty(PKP)wasperformed. BasicMechanismsofCornealCrosslinkingonKeratitis DuringtheprocedureofCXL,deepithelializationandcontact Atleastthreemechanismsmaycontributetothetherapeutic lensplacementincreasetheriskofinfection. effectofCXLoninfectiouskeratitis.Firstly,thecornea Risk Factors Therearesomeriskfactorsthatmay receivedCXLismoreresistanttothedigestionofproteaseor predisposeapatienttoacornealinfection:thecorneal collagenase.Spoerl [26] reportedthatthedissolutionof epitheliumdebridement,theapplicationofacontactlens,the corneawasobservedonday5,13and14inCXLtreated postoperativeoveruseofasteroidaldrop,ocularsurface porcinecorneasimmersedintrypsin,pepsinandcollagenase diseases(dryeye,blepharitis,keratoconjunctivitis, .)and solution,whilethecorrespondingtimewasday2,6and6in patient'spoorhygiene.Epithelialremovaldestroyedthe untreatedcorneas.Secondly,theexposuretoUVAorfree importantdefensebarrierofanintactcornealepithelium. [27] radicalsleadstothedamageofDNAofmicroorganism ,by Mostoftheocularpathogenscannotpassthroughanintact whicheliminatesorsuppressestheproliferationofpathogens. epithelium.Whentheepitheliumisremoved,thedefense Lastbutnotleast,thecornealstiffnessinducedbyCXLisa mechanismislossandbacteriaarefreetoinvadeintocornea[40]. [28] putativereasonfortheresistancetomelting . Ontheotherhand,theapplicationofsoftcontactlens THESECONDARYKERATITISDUETOCORNEAL increasestheriskofinfectionbecausebacteriamayadhereto CROSSLINKING theocularsurfaceandformbiofilmonthelens.Besides, DiverseSecondaryKeratitis AlthoughtheCXLtreatment contactlenschangestheocularsurfacebiochemistry.Those hasbeenutilizedininfectiouskeratitis,CXLitselfalsoleads riskfactorsmayreducetheresistanceofthecorneato [29] tovarietiesofcomplicationsincludingsecondarykeratitis . infection [41].Thepostoperativeoveruseofasteroidaldrop Thesephenomenahavebeenreportedbynumerousstudies maycreatetheriskforcornealinfection[42].Topicaloverusage performedCXLonpatientswithnon-infectiouscornea NSAIDscouldimpaircornealepithelialhealing,decrease disorders.1)Bacterialkeratitishasbeenreported3d corneal sensitivity,andinhibit theproliferationof followingCXL,andcornealscrapingrevealedanEscherichia keratocytes [43].Asidefromtheabove-mentionedriskfactors, coliinfection.Aftertreatment,thekeratitisresultedinan ocularsurfacediseases(dryeye,blepharitis,keratoconjunctivitis, avascularizedcornealscarandpermanentreductionofthe .)andpatient'spoorhygienemayplayanimportantrolein visualacuity [30].Anothercaseswhichshoweddifferent cornealinfection[33,39]. 1821 Differenteffectsofcornealcrosslinkingoninfectiouskeratitis DISCUSSION