Rev. Bras. Hematol. Hemoter. vol.36 número5

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

w w w . r b h h . o r g

Original

article

Sickle

cell

disease

retinopathy:

characterization

among

pediatric

and

teenage

patients

from

northeastern

Brazil

Dayse

Cury

de

Almeida

Oliveira

,

Magda

O.S.

Carvalho

,

Valma

Maria

Lopes

do

Nascimento

_,

_Flávia

_Silva

_Villas-Bôas

_,

Bernardo

Galvão-Castro

,

Marilda

Souza

Goncalves

c_{UniversidadeFederaldaBahia(UFBA),Salvador,BA,Brazil}

d_{CentrodePesquisaGonc¸aloMoniz-Fundac¸ãoOswaldoCruz-(CPqGM-FIOCRUZ),Salvador,BA,Brazil} e_{Fundac¸ãodeHematologiaeHemoterapiadoEstadodaBahia(HEMOBA),Salvador,BA,Brazil}

f_{InstitutoNacionaldeCiênciaeTecnologiadoSangue(INCT),Campinas,SP,Brazil}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received23April2014 Accepted2June2014 Availableonline18July2014

Keywords:

Sicklecellanemia DiseaseSC Retinopathy

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b

s

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t

Objective:Theaimofthepresentstudywastocharacterizesicklecelldiseaseretinopathy inchildrenandteenagersfromBahia,thestateinnortheasternBrazilwiththehighest incidenceandprevalenceofsicklecelldisease.

Methods:Agroupof51sicklecelldiseasepatients(36hemoglobinSSand15hemoglobin SC)withagesrangingfrom4to18yearswasstudied.Ophthalmologicalexaminationswere performedinallpatients.Moreover,afluoresceinangiographywasalsoperformedinover 10-year-oldpatients.

Results:Themostcommonocularlesionswerevasculartortuosity,whichwasfoundinnine (25%)hemoglobinSSpatients,andblacksunburst,inthree(20%)hemoglobinSCpatients. Peripheralarterialclosurewasobservedinfive(13.9%)hemoglobinSSpatientsandinthree (13.3%)hemoglobinSCpatients.Arteriovenousanastomoseswerepresentinsix(16.5%) hemoglobinSSpatientsandsix(37.5%)hemoglobinSCpatients.Neovascularizationwas notidentifiedinanyofthepatients.

Conclusions:Thisstudysupportstheuseofearlyophthalmologicalexaminationsinyoung sicklecelldiseasepatientstopreventtheprogressionofretinopathytoseverediseaseand furtherblindness.

©2014Associac¸ãoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.Published byElsevierEditoraLtda.Allrightsreserved.

∗ _{Correspondingauthorat:LaboratóriodeHematologia,GenéticaeBiologiaComputacional(LHGB),CentrodePesquisaGonc¸aloMoniz} (CPqGM),FIOCRUZ,RuaWaldemarFalcão,121,Candeal,40296-710Salvador,BA,Brazil.

E-mailaddress:[email protected](M.S.Goncalves).

http://dx.doi.org/10.1016/j.bjhh.2014.07.012

Introduction

Sicklecelldisease(SCD)ischaracterizedbythepresenceof thehemoglobinS (HbS)variantduetoa singlenucleotide change(GAG→GTG)intheˇ-globingene(HBB)thatreplacesa glutamicacidwithavalineatthesixthpositionofthe␤-globin chain.ThehemoglobinC(HbC)variantischaracterizedbya pointmutationatthesixthpositionoftheHBBgene,wherein alysinereplacesaglutamicacidatthesixthpositionofthe ␤-globinchain.1

Hb S has a high overall frequency worldwide; in Brazil its distributionisheterogeneous. Innortheastern Brazil,in particularinBahia, the populationhas atri-racial mixture ofEuropeans(mostlyPortuguese), Africansand indigenous Brazilians.2 _{Thefrequency ofHb Sin the stateofBahia is}

thehighestinBrazil,varyingfrom 4.5to14.7% indifferent populationgroups.3

Sicklecelldiseaseischaracterizedbyavarietyofclinical abnormalities that are frequently linkedto hemolytic ane-miaandthevaso-occlusiveprocessesoftenresponsibleforthe painandotherclinicalfeaturesdescribedbypatients, includ-ingretinopathy.1,4

Methods

The present study was approved by the Human Research EthicsBoardoftheFundac¸ãoOswaldoCruz(FIOCRUZ),and informedconsentwasobtainedfromtheguardiansof partici-pantsinaccordancewithethicalprinciplesandinaccordwith theHelsinkiDeclarationof1975andits revisions. Ophthal-mologicexaminationswerecarriedoutandperipheralblood sampleswerecollected onlyaftersignedinformed consent hasbeenobtained.

This cross-sectional study involved a group of 51 SCD patients(36HbSSand15HbSC)fromthestateofBahiain northeasternBrazilandwascarriedoutduringtheperiodof January2010toDecember2012.

Patientswererandomlyselected amongthose attending theHematologyOutpatientClinicattheFundac¸ãode Hema-tologiaeHemoterapiadaBahia(HEMOBA),areferralcenterfor SCDpatientswhoareseeninroutinevisits.Patientswerethen senttotheInstituto BrasileirodeOftalmologiaePrevenc¸ão daCegueira(IBOPC) foraneyeexamination,including fun-dus biomicroscopy and indirect binocular ophthalmoscopy inall patientsandfluoresceinangiographyinover 10-year-old patients. The following findings were observed in the fundoscopicexamination:vasculartortuosity,blacksunburst pattern,salmonpatchesandiridescentspots.Thepathologic classificationoffundoscopicalterationsasproliferativewas basedonGoldberg’sfivestagegrouping:stageI–peripheral arteriolarocclusions;stageII–peripheralarteriovenous anas-tomoses;stageIII–preretinalneovascularization;stageIV– vitreoushemorrhageandstageV–retinaldetachment.

Patientswithproliferativeretinopathywere stratified by ageandwereclassifiedasseverewhendisplayingstagesIII–V. Thehemoglobinpattern wasconfirmedintheHematology, GeneticandComputacional BiologyLaboratoryofFIOCRUZ and the Universidade Federal da Bahia (UFBA) using high

performance liquidchromatography (HPLC – Variant I/BIO-RAD,CA,USA).

SPSSversion18.0andGraphPadversion5.0wereusedto storeandanalyzethedata.Pearson’sChi-squaredorFisher’s exact tests were used to compare the two groups of SCD patientsasnecessary. Ap-valueofless than0.05 was con-sideredstatisticallysignificant.

Results

A total of 51 SCD patients were enrolled in this study: 36 (70.6%)withsicklecellanemia(SCA)orHbSSand15(29.4%) with Hb SC disease.Overall, the mean age ofthe patients was11.76±3.69 years.TheHb SSgrouphadameanageof 11.39±3.76years,and theHb SCgrouphad ameanageof 13.29±2.8years.Overall23(45%)SCDpatientswerefemale and 28 (55%) were male. In the Hb SS group, 19 patients (52.78%)weremaleand17(47.22%)werefemale,andinthe HbSCgroup,nine(60%)weremaleandsix(40%)werefemale. Visual acuitywas 20/20or 20/25forthe best eyesofall patients,correspondingto90%ofthetotalnumberofcases.

Age-relatedocularlesions,bothnon-proliferativeand pro-liferative (Goldberg) (Figs. 1–4), were very frequentin both

Figure1–Tortuousvesselsinan11-year-oldfemalewith hemoglobinSS.

Figure3–Salmonpatchesina13-year-oldmalewith hemoglobinSC.

groupsofpatients(HbSSandHbSC).Table1showsthe dis-tributionofocularlesionsacrossthetwoagegroups.TheHb SSgrouphadmoreocularchangesintheagerange0–9years old.IntheHbSCgroupofpatients,ocularchangesweremore frequentintheagerange10–18yearsold.

Vascular tortuosity and black sunbursts were the most commonfundoscopicocularlesionsfoundinbothSCDgroups (Hb SS and Hb SC). Table 2shows that vascular tortuosity lesionsweremostfrequentintheHbSSgroup.However,black sunburstlesionsweremorefrequentintheHbSCgroup. Iri-descentspotswerefoundinbothgroupsofSCDpatients.

Table3showsthedistributionofproliferativeocularlesions acrossGoldbergstagesI–VintheHb SSandHb SCpatient groups.Therewerepatientsinbothgroupswithproliferative ocularlesionsinGoldbergstagesIandII;however,theHbSS grouphadmoreproliferativeocularlesionsinthefirststage thantheHbSCgroup;thisincreasedwithageintheHbSC

Figure4–Peripheralarteriolarocclusionsand

arteriovenousanastomosesina14-year-oldmalewith hemoglobinSC.

group.Therewerenocasesofproliferativeocularlesionsat stagesIII–VineitherofthegroupsofSCDpatients.

Discussion

SeveralocularchangeswereobservedinthetwoSCDpatient groups;however,nochangeinvisualacuitywasfound,ashas previouslybeenreported.5–10

Fundoscopiclesions,suchasvasculartortuosityandblack sunbursts, were the mostfrequentchanges,in accordance withpreviousBrazilianreports.7–11 _{Theoverallfrequencyof}

vascular tortuosity was most frequently in SCA patients,

Table1–Thedistributionofretinalvesselocclusionlesionsacrosstwoagegroupsofsicklecelldiseasepatients.

Total(n=51) HemoglobinSC(n=15) HemoglobinSS(n=36) p-valuea

n % n % n %

Age(years)

0–9 4 36.4 – – 4 20.0 0.02

10–18 7 17.5 9 22.2 16 80.0 0.008

a _{Fisher’sexacttest}

Table2–Fundoscopicocularnon-proliferativelesionsinbothsicklecelldiseasegroups.

HemoglobinSS(n=36) HemoglobinSC(n=15) Total(n=51) p-valuea

n % n % n %

Vasculartortuosity 9 25.0 1 6.7 10 19.6 0.95

Blacksunburst 2 5.6 3 20.0 5 9.8

Salmonpatches – – 1 6.7 1 2.0

Angioidstreaks – – – – – –

Disksign – – – – – –

Iridescentspots 3 8.3 1 6.7 4 7.8

Total 14 38.9 6 40 20 39.3

Table3–ThedistributionofproliferativeocularlesionsforGoldbergstagesI–VinthehemoglobinSSandhemoglobinSC groups.

HemoglobinSS HemoglobinSC p-value Total

n % n % n %

Normal 25 69.4 6 40.0 0.09a _{31 60.8}

OcularLesions(Goldberg) 11 30.6 9 60.0 20 39.2

StageI 5 13.9 3 13.3 08 15.7

StageII 6 16.7 6 37.5 12 23.5

a _{YatescorrectedChi-squaretest.}

aspreviouslydescribed.10–12 _{Theblacksunburst lesionwas}

observed inboth groups, although its frequency in Hb SC patientswasmuchlowerthan thatdescribed inpreviously published studies.10–13 _{Salmon patch lesions were present}

onlyintheHbSCgroup;however,theiroccurrencehasbeen reportedinbothgroups albeitmorefrequentintheHb SC group.10–13 _{Iridescent spotswere foundinbothgroups, but}

theywere lesscommon than previouslyreported,which is probablybecausethesealterationsareatsitesofsalmonpatch resolutionandappearlessinyoungerpatients.14,15

Thisstudyindicatesthatretinalvasculardiseaseoccursin bothHbSSandHbSCpatientsandproliferativeretinopathies (Goldbergstages)beginearlyintheHbSSgroupandaremore commoninbothgroupswitholderages.11,12

Proliferativeretinopathy(stagesIII–V)wasnotobservedin ourstudy,probablyasthe patientswerevery youngrather than old.16–20 _{Fox et al.}19 _{studied Jamaican patients and}

observedthatocularproliferativelesionsinbothgenotypes increasewithage.

Conclusions

Theocularlesionsdescribedhereinmayhelptodefine stan-dardizedprotocolsinvolvingtheclinicalandophthalmologic follow-upofHbSSandHbSCpatientsespeciallyforyounger patients.MultipleocularcomplicationsexistforSCDpatients, andcontinuousassessmentisrequiredtodetectlesionsearly enoughforeffectiveprophylactictherapy.

Itisnecessaryto recommendthat SCDpatients receive periodicophthalmologicalexaminationsatearlyagesto pre-ventprogressionofthediseaseandearlyblindness,establish amoreeffectivetreatment,andassureabetterqualityofcare forpatients’eyes.

Funding

ThisstudywassupportedbytheConselhoNacionalde Desen-volvimentoCientífico e Tecnológico (CNPq)(311888/2013-5) (M.S.G.),the Fundac¸ãodeAmparo àPesquisa doEstadoda Bahia(FAPESB)SECTI/SESAB(3626/2013,1431040053063,and 9073/2007), the Instituto Nacional de Ciência e Tecnologia doSangue(INCTdoSangue-CNPq),and Fundac¸ãoOswaldo Cruz(FIOCRUZ)/MinistériodeSaúdedoBrasil;projectcode: MDTP1.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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