陨灶贼允韵责澡贼澡葬造皂燥造熏灾燥造援 6熏晕燥援 3熏 Jun.18, 圆园13 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 窑ClinicalResearch窑 Characteristicsofocularabnormalitiesingoutpatients

DepartmentofOphthalmology,theAffiliatedHospitalof changes. These features have important clinical MedicalCollegeofQingdaoUniversity,Qingdao266003, significanceinearlydetectionofthegoutandprevention ShandongProvince,China ofeyeinjury. Correspondence to: Gui-QiuZhao. Departmentof ·KEYWORDS: ocularabnormalities;gout;tophi Ophthalmology,theAffiliatedHospitalofMedicalCollege DOI:10.3980/j.issn.2222-3959.2013.03.09 ofQingdaoUniversity,Qingdao266003,ShandongProvince, [email protected] LinJ,ZhaoGQ,CheCY,YangSS,WangQ,LiCG.Characteristicsof Received:2012-09-11Accepted:2013-04-22 ocularabnormalitiesingoutpatients. 2013;6(3): 307-311 Abstract INTRODUCTION · AIM:Tocharacterizetheclinicalfeaturesofocular outisoneofthemostcommonauto-inflammatory surfaceingoutpatientsincoastalareaofShandong G arthritischaracterizedbytheriseofserumurateand ProvinceinChina. recurrentattacksofintra-articularcrystaldepositionof · METHODS:Atotalof380consecutivegoutpatients monosodiumurate (MSU),withaprevalenceof were examined from January 2011 to May 2011. approximately8per1000personsofallages [1,2].Boththe Accordingtothecourseofgout,patientsweredivided incidenceandtheprevalence ofgoutareincreasing intogroupA (<5years),B (5-10years)andC(>10 worldwide [3,4].Ratesofgouthaveapproximatelydoubled years).GroupD(controlgroup)wasconsistof50healthy between1990and2010 [5].Tophicanbefoundinthe subjects. Eyelids, lateral canthus, medial canthus, palpebral conjunctiva, sclera and cornea, anterior conjunctiva,cornea,iris,sclera,lensandothereyetissues, chamber,lens,anteriorvitreouswereexaminedbyslit andcancauseincreaseofintraocularpressure,inflammation [6-8] lamptofindwhetherthereweredepositionofuricacid of irisandciliary, andsoon . Though ocular crystals, ocular vascular tortuosity, redness and manifestationsofgouthavebeenreported,mostofthemare subconjunctivalhemorrhage.Theophthalmicexamsof casereports.Theclinicalfeaturesofgoutpatients'ocular visualacuity,intraocularpressure,funduswereusedto surfaceincoastalarea,however,havenotbeenwell assessanygout-relatedeyedisease. characterizedinliteratures. ·RESULTS:Uricacidcrystalswerefoundin3patients SUBJECTSANDMETHODS andthepositionsofthedepositewereincornealstroma, Subjects Thestudywasbasedonthedataof380gout cornealepitheliumandsuperficialstroma,andsclera patientsfromtheGoutStudyCenterintheAffiliated respectively.Theincidencewas0.79%.Dilatatedand HospitalofQingdaoUniversityMedicalCollegefrom tortuousbloodvesselsinconjunctivaandsclerasurface January2011toMay2011.Allpatientscamefromthe werefoundin38 (23.8%),40 (44.0%),58 (45.0%),9 coastalareasofShandongProvince. (18.0%)patientsingroupsA,B,CandD,respectively. AccordingtotheAmericanRheumatismAssociation ThedifferencesbetweengroupBandD,groupCandD DiagnosticCriteria(ACR)1997,goutwasdiagnosedwith werestatisticallysignificant( <0.01, <0.01).Transparent anyoneofthefollowingthreecriteria:1)specificfor vesicleswithmetal-likereflectedlightinsubconjunctiva synovialfluiduratecrystals,2)bychemicalmethodsor wereseenin26(16.2%),29(31.9%),41(31.8%),2(4.00%) patientsingroupsA,B,CandD,respectively.The polarizedlightmicroscopyconfirmedtophuscontainingurate differencesbetweenAandD,BandD,CandDwere crystals,or3)sixoutofthefollowing12features(clinical, statistically significant ( <0.05, <0.01, <0.01). laboratory,X-rayfindings):1)acutearthritisattacksmore Subconjunctivalhemorrhagewasfoundinallgroups,the thanonce;2)inflammatoryresponseinthepeakwithin1 differenceamongthefourgroupsshowednostatistically day;3)single-arthritisonset;4)visibleredjoints;5)thefirst significance. metatarsophalangealjointpainorswelling;6)unilateralfirst · CONCLUSION: Gout can cause ocular surface metatarsophalangealjointinvolvement;7)unilateraltarsal abnormalities,suchastophideposition,subconjunctival jointinvolvement;8)suspectedtophi;9)hyperuricemia;10) transparent vesicles and hemorrhage, and vascular asymmetricswellingwithinthejoint(X-rayconfirmed);11)

307 Ocularabnormalitiesingoutpatients

Figure1Threecasesofuricacidcrystalsdepositinocularsurface A:3whitecrystalsinthesuperficialstromaofcornea;B:A clusterofcrystalsintheepitheliumandsuperficiallayersofcornea;C:Thefluoresceinstainingofthesedeposits;D:Achalky-whitecrystal innasalsuperficialsclera. noboneerosionsubcutaneousbonecyst(X-rayconfirmed); 12)arthritissynovialfluidattackofbacterial culture negative,exceptforthosepatientswithsecondarygout. Atotalof380goutpatientsunderwentadetailedeye examinationbyanexperiencedophthalmologist.These patientsweredividedintogroupA,BandCaccordingtothe courseofdisease.GroupD(controlgroup)had50healthy subjectswhoseageswerebetween20and76.GroupA(<5 years)had160patientswithagesrangefrom18to72years old;groupB(5-10years)had91patientswithagesbetween 22and77yearsold;groupC(>10years)had129patients withagesrangefrom38to81yearsold.PatientsingroupD hadnohypertension,diabetes,goutandothersystemic Figure2Tophidepositswerefoundintheleftpoplitealfossa diseases. articularcapsule. Methods Visualacuity,intraocularpressureandfundus werecheckedroutinely.Eyelids,lateralcanthus,medial Otherpatientswhosedepositswereintheepitheliumand canthus,eyelidconjunctiva,scleraandcornea,anterior superficialstromaofcorneahada3-yearhistoryofgout.The chamber,lens,anteriorvitreouswereexaminedbyslitlamp righteyenearthebottommarginofthecornearevealeda tofindwhetherthereweredepositionofuricacidcrystals, clusterofirregular,flake-likecrystalsintheepitheliumand ocularvasculartortuousness,rednessorsubconjunctival superficiallayersofcornea,whichwasslightlyhigherthan hemorrhage.Topcon'sSL-DTCamerawasusedtomake incornealsurface (Figure1B).Thefluoresceinstainingof pictures. thedepositswasnegative(Figure1C).Noclinicalsignof StatisticalAnalysis SPSS17.0statisticalsoftwarepackage inflammationinoraroundthe depositswasfound. wasusedtoanalyzethesedata.Resultswerecomparedby Laboratoryanalysisrevealedsignificantincreaseofuricacid theChi-squaretest. <0.05wasconsideredstatistically (627 mol/L).Tophidepositswerefoundintheleftpopliteal 滋 significant. fossaarticularcapsule(Figure2). RESULTS Uricacidcrystaldepositwasfoundinscleraofthethird Uricacidcrystaldepositinocularsurface In380cases, patientwith12-yearhistoryofgout.Hisrighteyerevealeda uricacidcrystaldepositinocularsurfacewasfoundinthree chalky-whitecrystalwithirregularshape,measuringabout patients,theincidencewas0.79%.Twodepositswereinthe 3mm 4mminsizeinthenasalsuperficialsclera,separated cornea.Patientswhosedepositswereinthecortexofcornea 伊 fromtheothersclerabyaclearhighdensityring-likezone hada20-yearhistoryofgout.Botheyesrevealedamild (Figure1D).Noclinicalsignofinflammationinoraround hyperemiainconjunctivaandsuperficialofsclera,someof thecrystalswasfound.Thebloodvesselsof bulbar thebloodvesselsweretortuousandthickened.Threewhite crystalswithirregularshapewerefoundintherighteye, conjunctivathickenedandwereslightlytortuous.Moretophi eachmeasuringabout0.3mm 0.5mminthesuperficialstroma depositswereseeninbothearsandfeet.Laboratoryanalysis 伊 revealedincreaseduricacid(462 mol/L). ofcornea,separatedfromtheothertransparentcorneabya 滋 clearhighdensityring-likezone (Figure1A).Therewasno Tortuousvesselsintheconjunctivaandsclerasurface clinicalsignofinflammationinoraroundthecrystals. Wefoundmanypatientsofgouthadseriouslytortuous Laboratoryanalysisrevealedremarkableincreaseofuricacid vesselsintheconjunctivaandsclerasurface(Table1).Some (558 mol/L,normalrange,150-420)whenthecrystalswere ofthetortuousbloodvesselswerespiral(Figure 3A).Itwas 滋 foundforthefirsttime.Tophuswerefoundintherootsof observedthatmostofthecaseswereasymptomatic.The theleftindexfinger. tortuousvesselsintheconjunctivaandsclerasurfaceofthe 308 陨灶贼允韵责澡贼澡葬造皂燥造熏灾燥造援 6熏晕燥援 3熏 Jun.18, 圆园13 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

Figure3A:Tortuousbloodvesselswerefoundintheconjunctivaandsclerasurface;B:Transparentvesicleswithmetal-likereflectivein subconjunctivalwerefoundaroundthetortuousvessels;C:Subconjunctivalhemorrhage. goutpatientarenotunique.Therewere12patientsingroup Table 1 Tortuous vascular in the conjunctiva and sclera Dwhoalsohadtortuousbloodvesselsthoughnopatients 2 Groups Cases % χ a P hadspiralvessels.Thepercentageofpatientwithtortuous A(n=160) 38 23.8 0.725 >0.05 vesselswassignificantlyincreasedintheconjunctivaand B(n=91) 40 44.0 9.59 <0.01 sclerasurfaceingroupBandCcomparedwiththoseinthe C(n=129) 58 45.0 11.2 <0.01 groupD(<0.01,Table1).Whilethedifferencebetween D(n=50) 9 18.0 groupAandDwasnotstatisticallysignificant. 2 χ 17.4 Transparent vesicles with metal-like reflective in P <0.01 subconjunctiva Manypatientsinvolvedingoutwere 2 foundtohavetransparentvesicleswithmetal-likereflection χ a vs group D. insubconjunctiva(Table2).Mostofthevesicleswerefound Table 2 Transparent vesicles with metal-like reflection aroundthetortuousvessels(Figure3B).Transparentvesicles 2 Groups Cases % χ a P werefoundalsoingroupwithlowincidence.Anincreased A(n=160) 26 16.2 4.95 <0.05 percentage(>4times)oftransparentvesicleswasseenin B(n=91) 29 31.9 14.6 <0.01 groupAthanthatinDgroup.Thepercentageoftransparent C(n=129) 41 31.8 15.2 <0.01 vesiclesingroupBwassimilartothatinCgroupandnearly D(n=50) 2 4.0 twotimesmorethanthatingroupA(Table2). χ2 11.9 Subconjunctivalhemorrhage Therewere12 (7.50%),9 P <0.01 (9.90%),11(8.50%)patientswithsubconjunctivalhemorrhage 2 ingroupA,BandC,respectively(Figure3C).These χ a vs group D. hemorrhagewasmultifocal,spotandlittlepatchy,notlike Table 3 Subconjunctival hemorrhage theordinarylargeareasofsubconjunctivalhemorrhage. 2 Groups Cases % χ a P GroupDhadnosubconjunctivalhemorrhage(Table3).The A(n=160) 12 7.50 2.71 >0.05 subconjunctivalhemorrhagewasasymptomatic.Allpatients' B(n=91) 9 9.90 3.76 >0.05 visualacuityandintraocularpressurewasnormal. C(n=129) 11 8.50 3.18 >0.05 Tobramycinanddexamethasoneeyedropswereinstilled4 D(n=50) 0 timesadayfortwoweeks.Thehemorrhagehadnochange 2 χ 0.433 after2weeksandwasstillnotabsorbedafter3months. P >0.05 DISCUSSION 2 Inrecentyears,alargenumberofepidemiologicalstudies χ a vs group D. showthattheincidenceofgoutisincreasing.Theprevalence ofgoutreachedatleast1%ofpopulationinWestern proliferationoffibroustissueswellingbecausesodiumurate countries [8].Theincidenceofgoutreached1.14%inChina, crystalsdepositinthetissue.Accordingtothephysicaland especiallyinsomecoastalcities [10].Gouthasbecomea chemicaltheory,thehighertheuricacidandsupersaturation seriousdiseasewhichthreatshumanhealth.Butfew are,theeasierthecrystalsprecipitated.Theuricacid attentionshavebeenpaidtotheocularcomplicationcaused concentrationisveryhighinsomegoutpatients,but bygout.Inthisstudy,wescreenedatotalof380gout sometimesisnotsohigh.Itshowsthattheincidenceofuric patientsandfoundthatunusualocularcomplicationscaused acidcrystalsisnotonlyassociatedwithuricacid bygoutarefarbeyondpeople'simagination. concentration,butalsowithotherfactors.Theprocessof Tophiarenodulescausedbychronicinflammationandthe uricacidcrystals'dissolutionanddepositionisinvolvedin

309 Ocularabnormalitiesingoutpatients multifactorsandcouldresultinthephysicalandchemical conjunctivalandepiscleralvessels.Whenevaluatinga equilibriumstatefinally.Theoccurrenceofcrystallization patientwhoistroubledbybilateralchronicconjunctival canbecomprehendedthatthebalancetransfertothecrystal redness,theclinicianshouldconsidergoutinthedifferential orientationintheconditionofoneormorefactorschanged. diagnosis.Bakhritdinova [21] reportedaMorphometryofthe Intheeye,precipitationofuratecrystalhasbeendescribed bulbarconjunctivavesselsin50patientswithgoutwas ineyelids,tarsalplates,conjunctiva,cornea,sclera,tendons carriedoutbytelevisioncapillaroscopewithvideorecording. ofextraocularmuscles,orbit,andlens [11-18].Itwasreported Thefindingsindicatedthatmicrocirculatorydisordersstart thattophicanbedepositedintheirisorintheanterior withdilatationofthevenules,inwhicharteriolesand chamber,causinganterioruveitisorglaucoma [19].Inaddition capillariesareinvolved.Thisresultsinalterationofthe totheabovefactors,eyetophidepositionisalsoassociated arteriovenularcoefficientandofthebloodflowvelocityin withavarietyofspecialocularsurfacestructure.Ocular thecapillaries.Hence,themetabolicformofgoutmaybe structuresmaybeapoorersolventformonosodiumurate regardedastheinitialstageofdisease.Thesereportsare thanplasma;withhyperuricemia,theuratesbecome similartoourclinicalobservations.Thirtyeightpatientsin supersaturatedparticularlywithlowertemperatures.With groupAwerefoundwithocularsurfacechangesinblood prolongedhyperuricemia,crystalsandmicrotophidevelopin vessels, includingtortuosity,spiral,thick, conjunctival theconjunctiva.Inorganiccrystals,includingmonosodium congestion.ThesechangesingroupAconfirmedthe urate,canstimulatetheformationofspecificantibodies, vascularchangesinearlystage.Moreover,theincidencesof whichisabletorapidlyacceleratetheformationofnew ocularvascularchangesingroupBandCincreased crystals [20]. comparedto thatingroup A.Thedifferenceswere Weexaminedeyesof380goutpatientsanddiscovered3 statisticallysignificant.Inaddition,thepresenceofobjective patientswithuricacidcrystalsintheirocularsurface.These signsandthecourseofgoutwerecorrelated. patients' characteristicsincludingmedicalhistory,eye Therewere12,9,11patientsrespectivelyingroupA,Band examination,theshapeandthelocationofdepositsand Chadunexplainedasymptomaticsubconjunctivalhemorrhage without inflammationin ocularsurface,werehighly thatwasnotliketheordinarysubconjunctivalhemorrhage. consistentwiththosetophithatpreviouslyreportedin Thedifferencesamongthethreegroupswerenotstatistically literature.Sowehighlysuspectedthesedepositsastophi, significant(Table3).Ourfindingssuggestedthatthe especiallythepatientswithuricacidcrystaldepositsinthe hemorrhagehasnorelationshipwiththedurationofgout.As sclera,whoseeyeshadbeenophthalmologicalexamined8 weallknowthatmostordinarysubconjunctivalhemorrhage yearsagoandnocrystaldepositswerefoundinsclera wouldbeabsorbedin2to3weeks.Butthesubconjunctival surfaceatthattime.Weinferredthatwiththeprolonged hemorrhageingoutpatientshadnochangeafter2weeks hyperuricemia,uratecrystalsandmicrotophidevelopedin withTobramycinanddexamethasoneeyedropsinstilled thesclera.Thepatientalsohadmanytrophiinbothears, topicallyandwasnotabsorbedafter3months.Thisis fingerroots,feetandkidney.Thesemultipletophiwerenot anotherimportantpointthatcanmakeadistinctionbetween onlyduetothephysicalandchemicalfactors,hyperuricemia, subconjunctivalhemorrhageingoutpatientsandthatinother butalsotothehereditarysusceptibility.Theshapeofthe patients.Twentysix,29,41,2patientsinA,B,C,Dgroups depositsthatlocatedinthecortexofcorneawasverysimilar respectivelywerefoundtohavetransparentvesicleswith towhichlocatedinthesclera.Allofthemwereirregularly metal-likereflectioninsubconjunctival.Thedifferences shaped,chalky-whitecrystallinesubstances,roundedbya amonggroupA,B,Cwerestatisticallysignificant.Thisisa clearhighdensityring-likezone.Thereforeweproposedthat strongpointtoindicatethatthesevesiclesincreasedwiththe thesedepositswereassociatedwithgout.Thedepositshad courseofgout. nodirectrelationshipwiththecourseofgout,becausethere Thoughconfirmeduratecrystalsintheeyeswerereported wasonepatientwithdepositinocularsurfaceingroupsA, rarelyinthepast40years,theoccurrenceofocular B,Crespectively.Althoughmostpatientswithtophihave abnormality causedbygoutisfarbeyondpeople's hadgoutformanyyears,thepresenceofatophusmaybe imagination.Onereasonisthatthemajorityofgoutpatients' theinitialsignofthedisease [16].Serumuricacidlevels, ocular bnormalitiesareasymptomatic.Theotherreasonis ocularlocal specialorganizationalstructure,hereditary notonlypatientsbutalsoophthalmologistsareshortofthe susceptibility,flowvelocity,temperatureandotherfactors knowledgeofocular abnormalitycausedbygout. maycontrolthesituation. Ophthalmologistsshouldtakegoutintoaccountwhenthey Ferry [6] reportedthatthemostcommonabnormality discover a deposit,seriousocular vascularchanges, wasbilateralocularrednesscausedbyhyperemiaofthe metal-liketransparentvesiclesandmultifocal,spotandlittle 310 陨灶贼允韵责澡贼澡葬造皂燥造熏灾燥造援 6熏晕燥援 3熏 Jun.18, 圆园13 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 patchysubconjunctivalhemorrhageforthefirsttime.Further 9SaagKG,MikulsTR.Recentadvancesintheepidemiologyofgout. screeningofalargesamplewillbesummedupmoreocular 2005;7(3):235-241 abnormalitiesinpatientswithgoutandhelptodiagnosein 10MiaoZM,ZhaoSH,WangYG,ChenY,ChenXY,YanSL. theearlystageofgout. 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