w w w . e l s e v i e r . c o m / l o c a t e / b j i d
The
Brazilian
Journal
of
INFECTIOUS
DISEASES
Original
article
The
impact
of
ocular
tuberculosis
on
vision
after
two
months
of
intensive
therapy
Suzana
Batista
Vereza
de
Oliveira
a,
Ângelo
Ferreira
Passos
a,
David
Jamil
Hadad
b,
Lorena
Zbyszynski
a,
Pedro
Sousa
de
Almeida
Júnior
b,
Luiz
Guilherme
Schmidt
Castellani
b,
Reynaldo
Dietze
b,
Moisés
Palaci
b,∗aUniversidadeFederaldoEspíritoSanto,HospitalUniversitárioCassianoAntôniodeMoraes,DepartamentodeOftalmologia,Vitória,ES,
Brazil
bUniversidadeFederaldoEspíritoSanto,NúcleodeDoenc¸asInfecciosas,Vitória,ES,Brazil
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o
Articlehistory:
Received18December2017 Accepted9March2018 Availableonline19April2018
Keywords: Tuberculosis Eye Visualacuity Treatment
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Tuberculosisisaninfectiousdiseaseofglobalimportancewithmajoreconomicandsocial burdenaccountingfor25%ofallavoidabledeathsindevelopingcountries.Extrapulmonary involvementmayoccureitherinassociationwithclinicallyapparentpulmonary tubercu-losisorinisolation.Thiscross-sectionaldescriptivestudyaimedtoevaluatetheimpact ofoculartuberculosisinvisualacuityatbaselineandaftertwomonthsofintensive anti-tuberculoustherapy.Asampleof133pulmonarytuberculosispatients,sevendisseminated tuberculosis,andthreepleuraltuberculosispatientswasevaluated.Allpatientsunderwent routineophthalmicevaluation,includingassessmentofvisualacuity,biomicroscopy, appla-nationtonometry,indirectophthalmoscopy,andfluorescentangiographyasappropriate. Noneofthepatientshadimpairedvisualacuityduetotuberculosis.Arateof4.2%(6/143) ofocularinvolvementwasfound.Noneofthepatientswithocularinvolvementwere HIV-infected.Ofthesixpatientswithocularinvolvement,fivemetthediagnosticcriteriafor probableandoneforpossibleocularlesions.Asforthetypeofocularlesions,twopatients hadbilateralfindings:onehadsclerouveitisandthesecondhadchoroidalnodules.The otherfourpatientspresentedwithunilaterallesions:peripheralretinalarteryocclusionin therighteye(onecase),choroidalnodulesinthelefteye(onecase),andchoroidalnodulesin therighteye(twocases).Patientsprogressedfavorablyaftertwomonthofintensivetherapy, withnosignificantreductioninvision.
©2018SociedadeBrasileiradeInfectologia.PublishedbyElsevierEditoraLtda.Thisisan openaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/ by-nc-nd/4.0/).
∗ Correspondingauthor.
E-mailaddress:[email protected](M.Palaci). https://doi.org/10.1016/j.bjid.2018.03.005
1413-8670/©2018SociedadeBrasileiradeInfectologia.PublishedbyElsevierEditoraLtda.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
ofall avoidabledeathsin developingcountries. Themain clinicalformispulmonaryTB,but extrapulmonarydisease occursatvaryingfrequenciesinbothimmunocompetentand immunocompromised patients.2,3 Extrapulmonary
involve-ment,includingskin,kidney,centralnervoussystem,andeyes mayoccureitherinassociationwithclinicallyapparent pul-monaryTBorinisolation,withnoclinicalorbacteriological evidenceofpulmonaryinfection.OcularTBmayresultfrom hematogenous,primaryexogenous,ordirectcontiguity dis-semination.Hematogenousoriginisthemostcommonmode ofinfection.OcularTBmayinvolveocularadnexa(orbit, eye-lids,tearglands)aswellastheeyeglobe.4,5
Itcanbeespeciallydifficulttoidentify.Thecurrent limita-tionsofdiagnosticcriteriaandlackofaccurateinformationon eyediseasecouldbeattributedtoseveralfactors:(a)technical difficultiesandrisksofvisualimpairmentinvolvedinclinical specimen collection for definitive microbiological diagno-sis;(b)inaccurate diagnostic criteriausedin somestudies, includingpresumptivediagnosisbasedontreatmentresponse or strongtuberculin test reactors;(c)timing ofophthalmic examinationandTBtreatment(beforeorafterstarting treat-ment) as ocularlesions may regressor heal within weeks after anti-TB treatment initiation; and/or (d) the presence ofcomorbiditiesleading toan immunocompromised state, whichunderminesaneffectiveinflammatoryresponseand lesiondevelopment.6
TheprevalenceofocularTBvarieswidelyaroundtheworld. Fewwell-designedandcontrolledstudiesonocularTBhave beenconducted,butstilllittleisknownaboutitsimpacton vision.Studiestodatehaveonlyreportedthefrequencyof ocularTBandits clinicalmanifestationswithout assessing visualacuityorhaveexaminedasingleassessmentofvisual acuitywithoutmonitoringtheeffectsoftreatment.7–10 This
study aimed to assess visual acuity of TB patients before and after two months of treatment with anti-tuberculous therapy.
Patients
and
methods
Thiswasacross-sectionaldescriptivestudyapprovedbythe institutional review board of the Universidade Federal do Espírito Santo (UFES). A total of 177 bacteriologically con-firmedpulmonaryand/orextrapulmonaryTBpatientswere enrolled inthestudy. Patientswere interviewed,examined anddemographic,epidemiologicandclinicalinformationwas recordedinastandardizedquestionnaire.Informedconsent wasobtainedfromallparticipantsincludedinthestudy.At the hospital’s Ophthalmology clinic, two ophthalmologists examinedallpatients.Newlydiagnosedandbacteriologically confirmed TBpatients ofany sex, age, or HIVstatus were includedinthestudy.PatientswithapriorhistoryofTB,old chorioretinitislesionsobservedduringfundoscopiceye exam-ination, or self-reported treatment with anti-tuberculous medicationsduringtheprevioussixmonthswereexcluded.
theeye;(4)tonometrywithatonometer(Goldmann Tonome-ter,CarlZeissAT020);(5)binocularindirectophthalmoscopy withaHEINEBinocularIndirectOphthalmoscope(after mydri-asis with 1% tropicamide eye drops). In addition to the testsdescribedabove,onepatientalsounderwentfluorescent angiography(AFG)duetothepresenceofretinalvasculitis.
Diagnosisofoculartuberculosis
ThediagnosisofocularTBwasmadebasedonthecriteriafor “probable”and“possible”diseaseaccordingtoBousa,Merino, Sanchez-Munozand Carrilloclassification(1997).This diag-nosticclassificationusesathree-levelprobabilityscheme:(1) definitive diagnosis – isolationofMycobacterium tuberculosis fromeyespecimens;(2)probablediagnosis –isolationofM. tuberculosisfromextraoculartissuesorfluidswhenthereare ocular lesions consistent withTB infection in oneor both eyes(whichcannotbeattributedtoother causesandthere isadequateclinicalresponsetoanti-TBtreatment);(3) pos-sible diagnosis –same criteria as“probable” diagnosis, but with the inability toevaluatetreatment response duelack ofclinicalfollow-upofthepatient.Intraocularbiopsy spec-imens were not obtained as the patients enrolled in the study had been previouslydiagnosedwithTB.As such,no definitive diagnosis was made in our sample; only “prob-able” and “possible” levels were used for the diagnosis of ocularTB.
AllocularlesionsconsistentwithTBwerephotographed, and the patients were reassessed within 60 days. At that time, newphotographs were taken so that pre- and post-treatment photos could be compared and response to TB treatment could be ascertained (Fig. 1). An HIV test was offeredtoallpatientsduringthestudyperiod.Thosepatients withocularlesionsintheanteriorchamberwerealsotested forsyphilisusingtreponemaland nontreponemalserologic tests.
Patienttreatment
The study treatment regimens for pulmonary TB con-sisted of two months of daily isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E), followed by four months of daily HR (6-month standard short-course chemotherapy).11 At least five of the seven weekly doses
ofanti-tuberculosistreatmentwereadministeredbydirectly observed therapy. Patients with ocular TB followed offi-cial Brazilian guidelines for treating tuberculosis,19 which
recommend that all forms of extrapulmonary TB (except meningitis) should be treated for six months, as well as patients coinfected with HIV. Theprimary ophthalmologic outcome was evaluated aftertwo-months ofanti-TB treat-ment basedon previousstudies thatsuggestedafavorable therapeutic response by the end of intensive treatment phase.5,7
Fig.1–Compositeretinographyobtainedfrompatient1.Image(A)showstwochoroidalnoduleslocatedinthesuperior temporalarcadeoftherighteyebeforetuberculosistreatment,andimage(B)showsgrayishchoroidalscarsafter60daysof anti-tuberculosistherapy.
Statisticalanalysis
The sample consisted of 143 patients which equates to a samplingerrorof3.4ofanestimatedofpopulation1500new casesoftuberculosisinayearwithanexpectedprevalenceof 5%andasignificancelevelof5%.
The associations between the presence of tuberculous lesionsintheeyewithvisionoreyepressurewereassessed usingtheMann–WhitneyUtest.Tocomparethepresenceof tuberculouslesionsintheeyewiththeeyeexaminationsof priorandsuperiortosuchsegmentsandtheChi-squaretest wasrequired.
Results
Onehundredandseventy-sevenadultswithsuspected pul-monaryTBwereevaluatedforstudyparticipation.Thirty-four patientswereexcludedbecausetheydidnotmeetthe diag-nosticcriteriafortuberculosis.Ofthe143TBcasesenrolled inthestudy,133(93.7%)hadnewlydiagnosedinitialepisodes ofpulmonaryTB(culturepositive),seven(4.9%)had dissem-inated TB, and three (1.4%) had pleural TB. Patients’ ages rangedfrom18to79yearswithmeanageof36.6±11.8years. Themale-to-female ratiowas2.7–1.Onlysevenindividuals (4.9%)wereinpatientsatthetimeofenrollment,the remain-derwereevaluatedonanoutpatientbasis.Sixpatients(4.2%) wereco-infectedwithHIV,131(91.6%)testednegativeforHIV, andsix(4.2%)hadnoinformationavailableontheirHIV sta-tus.Presenceofcavitiesonchestradiographwasobservedin mostofthepatients(>70%).Tuberculinskintest(TST)was per-formedinallpatientsenrolledandastrongreactionwasseen inthreepatientswithocularTB.Ofallpatientsincludedinthe study,93(65%)hadnotstartedanti-TBtreatmentatthetime ofophthalmicevaluation,and43(30%)patientswereunder treatmentforlessthansevendays.OcularTBwasdiagnosedin 4.2%ofthepatients(6/142).Table1showsocularfindingsfrom bothpatientswithandwithoutocularTB.Fundoscopic exami-nationinpatientswithoutocularTBrevealedthatmost(>80%) hadnormalfundi,retinalvessels,opticnerves,andperipheral retinalvessels.Themainfindingsintheanteriorsegmentof
patientswithoutocularTBwereconjunctivitis(9.8%),followed bypterygium,andblepharitis,whileintheposteriorsegment werestaphylomaandglaucomatousexcavation.Most tuber-culosis patients(97.2%) showed good visualacuity. Results rangedfrom0.0to1.0(mean0.85±0.2)and0.1to1.0(mean 0.86±0.2)intherightandlefteyes,respectively.Therewas nostatisticallysignificantdifference(p>0.05)invisual acu-ity in patients with ocular pressure and without occular TB(Table2).However,dilatedfundusand anteriorsegment examinationrevealedhigherfrequencyofabnormalfindings (p<0.05)inposteriorsegmentofeyefrompatientswithocular TB(Table3).
OfthesixpatientswithocularTB,nonewereco-infected withHIV.Three wereinpatientsatthetimeof ophthalmo-logicalexaminationandthreewereevaluatedasoutpatients. Out of these six patients three had miliary TB. The cor-rectedvisual acuityranged from0.1 to1.0(mean 0.7±0.3) and 0.5 to 1.0 (mean 0.9±0.2) on the right and left eye, respectively. Two had bilateral involvement: one patient had sclerouveitis and the second had multiplenodules in choroid.Theotherfourpatientshadunilateralinvolvement: retinalvasculitisintheright eye(one case);choroidal nod-ules in the right eye (two cases); and choroidal nodules in the left eye (one case). Choroidal lesions were yellow-ish and ragged edged located at the posterior pole of the eyenodules. Agood therapeuticresponsewas observedin all patients with ocular TB. Regression of choroidal nod-ules(fourpatients)andretinalvasculitis (onepatient)were evidenced after twomonth ofTBtreatment (Table 4). Cor-ticosteroid therapy was not required in any patient since there were no serious lesions affecting optic disc and macula.
Discussion
OcularTBcaninvolveanypartoftheeyeandcanoccurwith orwithoutevidenceofsystemicTB.Amongpatientswith sys-temictuberculosis,ratesofocularinvolvementhavevaried. A1967study of10,524patientsinaBostonsanatorium,for example,reported arate ofocularinvolvementof 1.4%.In
WithoutocularTB
Anteriorsegment Normal 115 80.4% (73.0–86.6%) 115 80.4% (73.0–86.6%)
Pterygium 5 3.5% (1.1–8.0%) 5 3.5% (1.1–8.0%)
Cataract 0 0.0% (0.0–2.5%) 4 2.8% (0.0–2.5%)
Blepharitis 3 2.0% (0.4–6.0%) 3 2.1% (0.4–6.0%)
Conjunctivalnevus 0 0.0% (0.0–2.5%) 1 0.7% (0.0–3.8%)
Blepharitisandpterygium 3 2.0% (0.4–6.0%) 0 0.0% (0.0–2.5%)
Leukoma 1 0.7% (0.0–3.8%) 0 0.0% (0.0–2.5%)
Conjunctivitis 14 9.8% (5.5–15.9%) 14 9.8% (5.5–15.9%)
Notavailable 1 0.7% (0.0–3.8%) 1 0.7% (0.0–3.8%)
Posteriorsegment Normal 127 88.8% (82.5–93.5%) 127 88.8% (82.5–93.5%)
Staphyloma 0 0.0% (0.0–2.5%) 5 3.5% (1.1–8.0%)
Glaucomatousexcavation 3 2.1% (0.4–6.0%) 3 2.1% (0.4–6.0%)
Opticatrophy 0 0.0% (0.0–2.5%) 2 1.4% (0.2–5.0%)
Retinalhole 2 1.4% (0.2–5.0%) 0 0.0% (0.0–2.5%)
Retinalwhitewithoutpressure 1 0.7% (0.0–3.8%) 0 0.0% (0.0–2.5%)
Diabeticretinopathy 1 0.7% (0.0–3.8%) 0 0.0% (0.0–2.5%)
CRAOb 1 0.7% (0.0–3.8%) 0 0.0% (0.0–2.5%)
Myelinatedretinalnervefibers 0 0.0% (0.0–2.5%) 1 0.7% (0.0–3.8%)
Latticedegeneration 0 0.0% (0.0–2.5%) 1 0.7% (0.0–3.8%)
WithocularTB
Anteriorsegment Sclerouveitis 1 0.7% (0.0–3.8%) 1 0.7% (0.0–3.8%)
Posteriorsegment Choroidalnodule 3 2.10% (0.4–6.0%) 1 0.7% (0.0–3.8%)
Peripheralvascularobstruction 1 0.70% (0.0–3.8%) 0 0.0% (0.0–2.5%)
a Thegrandtotaldoesnotmatch100%becauseocularfindingmaybeofbothanteriorandposteriorsegmentofthesamepatient’seye. b Centralretinalarteryocclusion.
Table2–Visualacuityandintraocularpressureofnewlydiagnosedpatientswithpulmonary,disseminatedandpleural tuberculosis.
Eye Patients Totala p-valueb
WithocularTB WithoutocularTB
No. Median Mean SD No. Median Mean SD
Visualacuity Right 5 0.8 0.7 0.4 127 1.0 0.9 0.2 132 0.115
Left 6 0.8 0.7 0.2 126 1.0 0.9 0.2 132 0.028
Intraocularpressure Right 4 12.0 14.3 8.2 120 12.0 12.9 3.1 124 0.756
Left 4 16.5 17.8 6.9 119 12.0 13.9 8.9 123 0.211
a Visualacuitywerenotavailablein11patientsandtheintraocularpressureoftherightandlefteyeon19and20,respectively b Mann–Whitneytest.
Table3–Dilatedfundusandanteriorsegmentexaminationofnewlydiagnosedpatientswithpulmonary,disseminated andpleuraltuberculosis.
Eye Exam Patients p-valueb
WithocularTB WithoutocularTB
N % N %
Anteriorsegmenta Right Normal 5 83% 118 93%
0.385
Abnormal 1 17% 9 7%
Left Normal 4 67% 118 93%
0.023
Abnormal 2 33% 9 7%
Posteriorsegment Right Normal 1 17% 120 93%
<0.001
Abnormal 5 83% 9 7%
Left Normal 2 33% 119 92%
<0.001
Abnormal 4 67% 10 8%
a Twopatientshadnoassessmentfortheanteriorsegmentintheleftandrighteyes. b Chi-squaretest.
Table4–Therapeuticresponseafteratwo-monthintensiveanti-tuberculoustreatmentphase.
Patient Ag Eye VAa Daysontreatment:0(Baseline) Eye VAa Daysontreatment:2month
Ocularfinding Ocularfinding
Anteriorsegment Posteriorsegment Anteriorsegment Posteriorsegment
1 28/F Right 0.9 Normal Choroidalnodules Right 0.9 Normal Choroidalnodules
regression
Left 0.9 Normal Choroidalnodule Left 0.9 Normal Choroidalnodules
regression
2 62/M Right 0.8 Pterygium Choroidalnodules Right 0.8 Pterygium Choroidalnodules
regression
Left 0.6 Pterygium Normal Left 0.6 Pterygium Normal
3 79/F Right 1.0 Sclerouveitis Drusenandoptical
nerveexcavation
Right 1.0 Cured Drusenandoptical
nerveexcavation
Left 1.0 Sclerouveitis Drusen Left 1.0 Cured Drusen
4 34/M Right 1.0 Normal Normal Right 1.0 Normal Normal
Left 1.0 Normal Choroidalnodule Left 1.0 Normal Choroidalnodules
regression
5 22/M Right 1.0 Normal Choroidalnodule Right 1.0 Normal Choroidalnodules
regression
Left 1.0 Normal Normal Left 1.0 Normal Normal
6 47/M Right 1.0 Normal Drusenandoptical
diskexcavation, retinalvasculitis.
Right 1.0 Normal Drusen,opticaldisk
excavationand retinalvasculitis regression
Left 0.5 Normal Opticaldisk
excavation
Left 0.5 Normal Opticaldisk
excavation
contrast,a study in1997in 100hospitalized patients with tuberculosisinSpainreportedarateofocularinvolvementof 18%.5Recently,LaraandOcampodescribed6.8%ofocularTB
in103pulmonaryTBpatientsevaluatedinatertiaryhospital inthePhilippines,andMehtaetal.reported12.7%presumed ocularTBin47HIV/MDR-TBco-infectedpatientsinMumbai, India.12,13ThefrequencyofocularTBfoundinourstudy(4.2%)
lieswithinthemeanrangedescribedintheliterature.5,6,8–10
Asidefrom casereports, the onlytwo Brazilian studies onocularTBreportedfrequenciesrangingbetween0%and 5.5%.8,10However,thesestudieshavemethodologicalbiases
thatpreventedareliablecomparisonoffrequencies.Inone studytheauthorsevaluatedonlynon-HIV-infectedinpatients atdifferenttimepointsoftreatment,whichmayexplainwhy noocularlesionswerefound.Thesecondstudywasaffected byselectionbias.Ofthe16casesclassifiedasocularTB,only 56%werebacteriologicallyconfirmedinanotherorgan,and sixof16(38%)wereHIV-infected.
AfterdiagnosisofocularTB,anyofthethreecategories,5
itisimportanttoassessvisionacuity.Allpatientsincluded inour study were suspected ofhaving TBat the moment of ophthalmic evaluation and at that time there were no visualcomplaints, exceptwhencomorbidities were associ-ated.Therefore,itisimportanttopointoutthateventhesix patientswhowerediagnosedwithocularTBinourstudy,only onehadvision<0.6,probablyassociatedwithglaucoma. As wehaveevaluatedpatientswithnovisioncomplaints,it is possiblethattheextensionoflesionswasnotsevereenough toaffectthevisualacuityatthatmomentofophthalmologic evaluation.
In a study conducted in Spain, visual acuity of 100 TB patients was assessed before and after treatment. The
average visual acuity in patients with ocular involvement waslower (0.69±0.2) thaninthosewithnoocular involve-ment (0.9±0.2). Theauthors described improved acuity in patientswithhealedlesionsandarguedthatocularTBaffects vision.6 However,informationonthe exacttimingofthese
assessments (at baselineand end of study) and treatment wasnotdocumented.InanotherstudyconductedinBurundi (Africa)in154AIDSpatients,although61%wereco-infected withTB,ocularTBwasnotdescribed.Visualacuityof20/30 or more was reported in 80% of the eyes evaluated.9 In
a study carried out in Brazil, Mendes et al. evaluated 292 patients withTBand found5.5%with ocularinvolvement. Themost common ocularlesions were choroidaltubercles (75%). Ophthalmic examinations were not timed with the treatment regimen and visual acuity was not monitored duringtreatment.However,theauthorsclaimedthatTBdid notaffectvisionsinceonly18.75%ofthepatientshadvisual acuitybetterthan20/25.8
OutofthesixpatientswithocularTBinourstudy,three (50%)werehospitalizedupondiagnosis(initialinvestigation) andhadmiliaryTB.ItisbelievedthatmiliaryTBisarisk fac-torforoculardisease.14InBrazil,Mendesetal.showedthat
seven(38%)of18patientswithocularTBhadmiliarydisease (OR=8.1395%CI1.06–62.4).8Noneofthesixpatientsinour
studyhadreducedvisualacuityduetoTB.Infact,fiveofthe sixpatientshadclosetonormal(≥0.8)visualacuity,andone patienthadpoorvisionduetoadvancedglaucoma.
Choroidalnoduleswere foundinfourofthesixpatients (cases#1,2,4and5).Onepatienthadbilateralsclerouveitis andonehadtemporalretinalvasculitisintherighteye.The highestnumberofnodulesfoundpereyewastwo,although theliteraturehasreportedasmanyas10–20nodulespereye.
thinningandtransparencyoftheunderlyingchoroid(case#3). In1941,WoodsarguedthatTBwasaprimarycauseofuveitis in80%ofcases.However,inhis1960review,herecognizedthis ratewaslikelymuchlower–around20%.Inthe1990s,Weiner andBezerrareporteda0.75%rateofuveitis.These inconsis-tentfindingspointingtowardlowerratesmaybeexplainedby thedevelopmentofnewdiagnostictechnologiesandmethods, includinglaboratory techniquesallowingformoreaccurate differentialdiagnosesofthisformofoculardisease.16,17
Ourstudyfoundonlyonecaseofretinalvasculitis(case#6). Thefirstexaminationclearlyshowedareasofsuperficialand deepretinalhemorrhageandperipheraltemporalvasculitis intherighteye.AFGshowedextensiveareasofretinal non-perfusionassociatedwithcontrastuptakeinthewallsofthe affectedvessels.AfterTBtreatmentthelesionsregressedand lasertherapywasnotrequiredasanadjunctivetreatment.
In2001,Guptaandcolleaguesevaluated13patientswith PCRanalysispositiveforTBinaqueousandvitreous spec-imens. They found neovascularization in 11 eyes (57.8%), retinalhemorrhagesin10(52.6%),preretinalorvitreous hem-orrhages in five (26.3%) and these lesions regressed in all casesaftera12-monthtreatment. Afterchoroidalnodules, periphlebitisisbelievedtobethesecondmostimportant ocu-larmanifestationofTB.18,19
Inour study,all lesionswere resolved infive ofthe six patientsstudiedatthe 60-dayfollow up. Two patientshad lightlypigmentedgraychoroidalnodulessuggestiveof heal-ing.One nodule was completely resolved with no scaring. The case ofretinal vasculitis showed resolution of vascu-lar inflammation and resorption of the hemorrhage. One case was lost to follow-up. All patients underwent oph-thalmicexaminationwithinfourdaysofspecifictreatment initiationandtheyall showednosignsoflesionresolution atthat time point. Other authors have claimedthat heal-ing occurs around week eight of treatment. It is possible that treatment response occurs earlier than 60 days, but intermediateevaluationsare necessaryforamoreaccurate assessment.
In conclusion, TB-related ocular involvement (4.2%) included mostly choroidal nodules that progressed favor-ablyaftertwomonthsofintensiveanti-tuberculoustherapy, without causing any significant reduction in visual acuity. Althoughwehaveobservednoeyedamageafterspecific treat-ment,anaccurateearlydiagnosisofocularTBmaybecritical forpreventingcomplications,suchasretinal neovasculariza-tion,thatcancauseimpairedvisionorblindnessifuntreated. Moreover,sinceeyeexaminationisnotroutinelyperformed inallTBpatients,itislikelythatdisseminatedTBis underre-portedworldwide.
Financial
support
Thisworkwassupportedbymaster’sgrant;partnership Petro-brás–UniversidadeFederaldoEspíritoSanto.
Acknowledgements
WewouldliketothankThiagoMachadodeOliveiraandDaniel SchottTeixeiradaSilva,bothfromBostonUniversitySchool ofMedicine,fortheirassistanceineditingandtranslatingthis text.
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e
s
1.MurrayCJ,StybloK,RouillonA.Tuberculosisindeveloping countries:burden,interventionandcost.BullIntUnion TubercLungDis.1990;65:6–24.
2.WHO.Globaltuberculosiscontrol–surveillance,planning, financing.Geneva,Switzerland;2006.
3.MinistériodaSaúde.Fundac¸ãoNacionaldeSaúde.Controle daTuberculose:UmaPropostadeIntegrac¸ãoEnsino-Servic¸o. 5thed.RiodeJaneiro,Brazil;2002.
4.HelmCJ,HollandGN.Oculartuberculosis.SurvOphthalmol. 1993;38:229–56.
5.BousaE,MerinoP,Mu ˜nozP,Sanchez-CarrilloC,Yá ˜nezJ, CortésC.Oculartuberculosis–aprospectivestudyina generalhospital.Medicine.1997;76:53–61.
6.BeareNAV,KublinJG,LewisDK,etal.Oculardiseasein patientswithtuberculosisandHIVpresentingwithfeverin Africa.BrJOphthlmol.2002;86:1076–84.
7.MendesGF,ToribioRC,AlvaresTA,AlvaresRRA.Alterac¸ões fundoscópicasesuaassociac¸ãoclínicaempacientescom tuberculose,noDistritoFederal.ArqBrasOftalmol. 2003;66:359–64.
8.CochereauI,Mika-CabanneN,GodinaudP,etal.AIDSrelated eyediseaseinBurundi,Africa.BrJOphthalmol.
1999;83:339–42.
9.OréficeF,CarvalhoAZ,PinheiroSRA.Controvérsiasnas uveítestuberculosas.ArqBrasOftalmol.
1997;50:237–45.
10.BicasH.Visualacuity:measurementsandnotations.ArqBras Oftalmol.2002;65:375–84.
11.MinistériodaSaúde.Manualderecomendac¸õesparao controledatuberculosenoBrasil.Brasília,Brazil:Secretaria deVigilânciaemSaúde,DepartamentodeVigilância Epidemiológica;2011,284pp.
12.LaraLPR,OcampoVJr.Prevalenceofpresumedocular tuberculosisamongpulmonarytuberculosispatientsina tertiaryhospitalinthePhilippines.JOphthalmicInflamm Infect.2013;3:1.
13.MehtaS,IsaakidisP.Ocularinflammatorydiseaseandocular tuberculosisinacohortofpatientsco-infectedwithand multidrug-resistanttuberculosisinMumbaiIndia:a cross-sectionalstudy.BMCInfectDis.
2013;12:225.
14.IllingworthRS,WrightT.Tuberclesofthechoroids.BrMedJ. 1948;4572:364–8.
15.OlazabalFJr.Choroidaltubercles.Aneglectedsign.JAMA. 1967;200:104–7.
16.MassaroD,KatzS,SachsM.Choroidaltubercles.Aclueto hematogenoustuberculosis.AnnInternMed.1964;60: 231–41.
17.ThompsonMJ,AlbertDM.Oculartuberculosis.Arch Ophthalmol.2005;23:844–9.
18.RosenPH,SpaltonDJ,GrahamEM.Intraoculartuberculosis. Eye.1990;4Pt3:486–92.
19.GuptaV,GuptaA,AroraS,BamberyP,DograMR,AgarwalA. Presumedtubercularserpiginous-likecoroiditis:clinical presentationandmanagement.Ophthalmology. 2003;110:1744–9.
