Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration

52 Pages·2017·0.9 MB·English

CochraneDatabaseofSystematicReviews
Antioxidant vitamin and mineral supplements for preventing
age-related macular degeneration (Review)
EvansJR,LawrensonJG
EvansJR,LawrensonJG.
Antioxidantvitaminandmineralsupplementsforpreventingage-relatedmaculardegeneration.
CochraneDatabaseofSystematicReviews2012,Issue6.Art.No.:CD000253.
DOI:10.1002/14651858.CD000253.pub3.
www.cochranelibrary.com
Antioxidantvitaminandmineralsupplementsforpreventingage-relatedmaculardegeneration(Review)
Copyright©2012TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
SUMMARYOFFINDINGSFORTHEMAINCOMPARISON . . . . . . . . . . . . . . . . . . . 3
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Figure1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Figure2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
ADDITIONALSUMMARYOFFINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . . 9
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
DATAANDANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Analysis1.1.Comparison1Anyantioxidantversusplacebo,Outcome1AMD. . . . . . . . . . . . . . 38
Analysis1.2.Comparison1Anyantioxidantversusplacebo,Outcome2AdvancedAMD. . . . . . . . . . 39
Analysis2.1.Comparison2Alpha-tocopherolversusplacebo,Outcome1AMD. . . . . . . . . . . . . . 40
Analysis2.2.Comparison2Alpha-tocopherolversusplacebo,Outcome2AdvancedAMD. . . . . . . . . . 40
Analysis3.1.Comparison3Beta-caroteneversusplacebo,Outcome1AMD. . . . . . . . . . . . . . . 41
Analysis3.2.Comparison3Beta-caroteneversusplacebo,Outcome2AdvancedAMD. . . . . . . . . . . 42
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
WHAT’SNEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
SOURCESOFSUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
INDEXTERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Antioxidantvitaminandmineralsupplementsforpreventingage-relatedmaculardegeneration(Review) i
Copyright©2012TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[InterventionReview]
Antioxidant vitamin and mineral supplements for preventing
age-related macular degeneration
JenniferREvans1,JohnGLawrenson2
1CochraneEyesandVisionGroup,ICEH,LondonSchoolofHygiene&TropicalMedicine,London,UK.2DivisionofOptometry
&VisualScience,CityUniversity,London,UK
Contactaddress:JenniferREvans,CochraneEyesandVisionGroup,ICEH,LondonSchoolofHygiene&TropicalMedicine,Keppel
Street,London,WC1E7HT,[email protected].
Editorialgroup:CochraneEyesandVisionGroup.
Publicationstatusanddate:Newsearchforstudiesandcontentupdated(nochangetoconclusions),publishedinIssue6,2012.
Citation: EvansJR,LawrensonJG.Antioxidantvitaminandmineralsupplementsforpreventingage-relatedmaculardegeneration.
CochraneDatabaseofSystematicReviews2012,Issue6.Art.No.:CD000253.DOI:10.1002/14651858.CD000253.pub3.
Copyright©2012TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
Thereisinconclusiveevidencefromobservationalstudiestosuggestthatpeoplewhoeatadietrichinantioxidantvitamins(carotenoids,
vitaminsCandE)orminerals(seleniumandzinc)maybelesslikelytodevelopage-relatedmaculardegeneration(AMD).
Objectives
ToexaminetheevidenceastowhetherornottakingantioxidantvitaminormineralsupplementspreventsthedevelopmentofAMD.
Searchmethods
WesearchedCENTRAL(which contains theCochrane EyesandVision GroupTrialsRegister) (TheCochrane Library2011, Issue
12),MEDLINE(January1950toJanuary2012),EMBASE(January1980toJanuary2012),OpenGrey(SystemforInformationon
GreyLiteratureinEurope)(www.opengrey.eu/),themetaRegisterofControlledTrials(mRCT)(www.controlled-trials.com),Clinical-
Trials.gov(www.clinicaltrials.gov)andtheWHOInternationalClinicalTrialsRegistryPlatform(ICTRP)(www.who.int/ictrp/search/
en).Therewerenodateorlanguagerestrictionsintheelectronicsearchesfortrials.Theelectronicdatabaseswerelastsearchedon26
January2012.
Selectioncriteria
We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin and/or mineral supplement (alone or in
combination)tocontrol.
Datacollectionandanalysis
Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into
RevMan5andtheotherauthorcheckedthedataentry.Wepooleddatausingafixed-effectmodel.
Mainresults
WeincludedfourRCTsinthisreview;62,520peoplewereincludedintheanalyses.ThetrialswereconductedinAustralia,Finland
andtheUSAandinvestigatedvitaminEandbeta-carotenesupplements.Overallthequalityoftheevidencewashigh.Peoplewhotook
thesesupplementswerenotatdecreased(orincreased)riskofdevelopingAMD.Thepooledriskratioforanyantioxidantsupplement
inthepreventionofanyAMDwas0.98(95%confidenceinterval0.89to1.08)andforadvancedAMDwas1.05(95%CI0.80to
1.39).Similarresultswereseenwhentheanalyseswererestrictedtobeta-caroteneandalpha-tocopherolalone.
Antioxidantvitaminandmineralsupplementsforpreventingage-relatedmaculardegeneration(Review) 1
Copyright©2012TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Authors’conclusions
ThereisaccumulatingevidencethattakingvitaminEorbeta-carotenesupplementswillnotpreventordelaytheonsetofAMD.There
is no evidence with respect to other antioxidant supplements, such as vitamin C, lutein and zeaxanthin, or any of the commonly
marketedmultivitamincombinations. Althoughgenerallyregardedassafe,vitaminsupplementsmayhaveharmfuleffectsandclear
evidenceofbenefitisneededbeforetheycanberecommended.PeoplewithAMDshouldseetherelatedCochranereview’Antioxidant
vitaminandmineralsupplementsforslowingtheprogressionofage-relatedmaculardegeneration’writtenbythesamereviewteam.
PLAIN LANGUAGE SUMMARY
Antioxidantvitaminsandmineralsupplementstopreventthedevelopmentofage-relatedmaculardegeneration
Age-related macular degeneration (AMD) is a condition affecting the central area of the retina (back of the eye). The retina can
deterioratewithageandsomepeoplegetlesionsthatcanleadtolossofcentralvision.Somestudieshavesuggestedthatpeoplewho
eatadietrichinantioxidantvitamins(carotenoids,vitaminsCandE)orminerals(seleniumandzinc)maybelesslikelytogetAMD.
Theauthorsidentifiedfourlarge,high-qualityrandomisedcontrolledtrialswhichincluded62,520people.Thetrialswereconducted
inAustralia,FinlandandtheUSAandinvestigatedtheeffectsofvitaminEandbeta-carotenesupplementation.Thesetrialsprovide
evidencethattakingvitaminEandbeta-carotenesupplementsisunlikelytopreventtheonsetofAMD.Therewasnoevidencefor
otherantioxidantsupplementsandcommonlymarketedcombinations.Althoughgenerallyregardedassafe,vitaminsupplementsmay
haveharmfuleffectsandclearevidenceofbenefitisneededbeforetheycanberecommended.
Antioxidantvitaminandmineralsupplementsforpreventingage-relatedmaculardegeneration(Review) 2
Copyright©2012TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
CoAn SUMMARY OF FINDINGS FOR THE MAIN COMPARISON [Explanation]
pyright©tioxidant
201vita AntioxidantsupplementcomparedwithplaceboforpreventionofAMD
2m
Thin
ean Patientorpopulation:generalpopulation
Cd
ocm Settings:community
hraine Intervention:vitaminE
neral Comparison:placebo
Cs
ollaboupplem Outcomes Illustrativecomparativerisks* (95%CI) Relativeeffect Noofparticipants Qualityoftheevidence Comments
ration.entsfo (95%CI) (studies) (GRADE)
Pr
ublishpreve Assumedrisk Correspondingrisk
edbntin Placebo Antioxidant supple-
yg mentation
Johage
nWiley-related AnyAMD 180per1000 1(18519pteor210040)0 RR0.97(0.85to1.09) 4(40),887 ⊕hi⊕gh⊕⊕
&m
Sa
oncu AdvancedAMD 6per1000 8per1000 RR1.34(0.84to2.14) 40,887 ⊕⊕⊕⊕
s,Ltdlarde (5to13) (4) high
.g
e
n
er *The basis for the assumedrisk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95%confidence interval) is
a
tio basedontheassumedriskinthecomparisongroupandtherelativeeffectof theintervention(andits95%CI).
n
(R AMD:age-relatedmaculardegeneration;CI:confidenceinterval;RR:riskratio
e
v
ie
w GRADEWorkingGroupgradesof evidence
)
Highquality:Furtherresearchisveryunlikelytochangeourconfidenceintheestimateof effect.
Moderatequality:Furtherresearchislikelytohaveanimportantimpactonourconfidenceintheestimateof effectandmaychangetheestimate.
Lowquality:Furtherresearchisverylikelytohaveanimportantimpactonourconfidenceintheestimateof effectandislikelytochangetheestimate.
Verylowquality:Weareveryuncertainabouttheestimate.
3
BACKGROUND Whyitisimportanttodothisreview
Antioxidantvitaminandmineralsupplementsareincreasinglybe-
ingmarketedforuseinage-relatedeyedisease,includingAMD.
Descriptionofthecondition Theaimofthisreviewwastoexaminetheevidenceastowhetheror
nottakingvitaminormineralsupplementspreventsthedevelop-
Age-relatedmaculardegeneration(AMD)isadiseaseaffectingthe
mentofAMD.SeealsotherelatedCochranereview’Antioxidant
centralareaoftheretina(macula).Intheearlystagesofthedis-
vitaminandmineralsupplementsforslowingtheprogressionof
easelipidmaterialaccumulatesindepositsunderneaththeretinal
AMD’whichconsiderswhethersupplementationforpeoplewith
pigmentepithelium.Thesedepositsareknownasdrusen,andcan
AMDslowsdowntheprogressionofthedisease(Evans2006).
beseenaspaleyellowspotsontheretina.Thepigmentofthereti-
nalpigmentepitheliummaybecomedisturbed,withareasofhy-
perpigmentationandhypopigmentation.Inthelaterstagesofthe
disease,theretinalpigmentepitheliummayatrophycompletely.
OBJECTIVES
Thislosscanoccurinsmallfocalareasorcanbewidespread(ge-
ographic).Insomecases,newbloodvesselsgrowunderthereti- To determine whetherantioxidant vitamin and/or mineral sup-
nalpigmentepitheliumandoccasionallyintothesubretinalspace plementationpreventsthedevelopmentofAMD.
(exudativeorneovascular).Haemorrhagecanoccurwhichoften
resultsinincreasedscarringoftheretina.
Theearlystagesofthediseaseareingeneralasymptomatic.Inthe
METHODS
laterstagestheremaybeconsiderabledistortionwithinthecentral
visualfieldleadingtoacompletelossofcentralvisualfunction.
Population-basedstudiessuggestthat,inpeople65yearsandolder,
Criteriaforconsideringstudiesforthisreview
approximately5%haveadvancedAMD(Owen2012).Itisthe
mostcommoncauseofblindnessandvisualimpairmentinindus-
trialisedcountries.IntheUKforexample,over30,000peopleare
Typesofstudies
registeredasblindorpartiallysightedannually,halfofwhomhave
Weincludedrandomisedcontrolledtrials(RCTs)comparingan-
losttheirvisionduetomaculardegeneration(Bunce2006).
tioxidant vitamin and/or mineral supplementation (alone or in
combination)tocontrol.
Descriptionoftheintervention
Typesofparticipants
Photoreceptorsintheretinaaresubjecttooxidativestressthrough-
Participants in the trialswere people in the general population,
out life due to combined exposures to light and oxygen. It has
withorwithoutdiseasesotherthanAMD.Weexcludedtrialsin
beenproposedthatantioxidantsmaypreventcellulardamagein
whichtheparticipantswereexclusivelypeoplewithAMD.These
theretinabyreactingwithfreeradicalsproducedintheprocessof
trialsareconsideredinaseparateCochranereviewexaminingthe
lightabsorption(Christen1996).
effect of supplementation on progression of the disease (Evans
Thereareanumberofnon-experimentalstudiesthathaveexam-
2006).
inedthepossibleassociationbetweenantioxidantmicronutrients
andAMD,althoughfewstudieshaveexaminedsupplementation
specifically(Chong2007;Evans2001).Dataonvitamin intake Typesofinterventions
inobservationalstudiesshouldbeconsideredcautiouslyaspeople Antioxidants were defined as any vitamin or mineral which is
whohaveadietrichinantioxidantvitaminsandminerals,orwho knowntohaveantioxidantpropertiesinvivoorwhichisknown
choosetotakesupplementsregularly,aredifferentinmanyways tobeanimportantcomponentofanantioxidantenzymepresent
fromthosewhodonot;thesedifferencesmaynotbeadequately intheretina.Weconsideredthefollowing:vitaminC,vitaminE,
controlledbystatisticalanalysis.Theresultsoftheseobservational carotenoids(includingthemaculapigmentcarotenoidsluteinand
studieshavebeeninconclusive. zeaxanthin),seleniumandzinc.
Typesofoutcomemeasures
Howtheinterventionmightwork
Thefollowingoutcomeswereused:
The underlying theory is that antioxidant vitamin and mineral 1. numberofparticipantsdevelopingAMD;
supplementswillprotecttheretinaagainstoxidativestressandthat 2. numberofparticipantswithvisuallossduetoAMD;
thisprotectionwilldelaytheonsetofAMD. 3. qualityoflifemeasures;
Antioxidantvitaminandmineralsupplementsforpreventingage-relatedmaculardegeneration(Review) 4
Copyright©2012TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
4. anyadverseoutcomesreported. Selectionofstudies
Weusedthefollowingdefinitions:
Ourinitialsearchesidentifiedalltrialsofantioxidantsupplements
AMD:thiswastakenasdefinedbytrialinvestigators.Itiscom-
and therefore generated many citations. Each review author as-
monly defined as: in the macular area 3000 microns diameter
sessedhalfofthetitlesandabstractsresultingfromthesearches
fromfovea:drusenwithorwithoutpigmentaryabnormalitiesor
andselectedstudiesaccording tothedefinitions inthe’Criteria
geographicatrophyorcharacteristicchoroidalneovascularisation
forconsideringstudiesforthisreview’.Tocheckthatwewerecon-
withnoothercause.Wherepossible, wehaveusedtheAge-Re-
sistent,webothassessedasubsetof100recordsandcomparedre-
latedEyeDiseaseStudySystemforclassifyingage-relatedmacular
sults.Weobtainedfullcopiesofallreportsreferringtocontrolled
degeneration(AREDS2001b).Inparticular,theterm’advanced
trialsthatdefinitelyorpotentiallymettheinclusioncriteria.We
AMD’referstogeographicatrophyorneovascularAMD.
assessedthefullcopiesandselectedstudiesaccording tothein-
Visualloss:anywell-definedoutcomebasedonvisualacuitywas
clusioncriteria.Wewrotetoauthorsoftrialsforwhichtherewere
useddependingonthewayinwhichauthorspresentedtrialdata.
no published outcome data on AMD to ask whether they had
Quality of life: any validated measurement scale which aims to
collectedanydataoneyediseaseoutcomes.
measure the impact of visual function loss on quality of life of
Asnoneofthetrialsrespondedpositively,i.e.gaveusunpublished
participants.
dataonAMD,forfurtherupdatesofthisreviewweonlyconsid-
eredtrialswithpublisheddataonAMD.
Inupdatestothisreview,bothauthorswentthroughthetitlesand
Searchmethodsforidentificationofstudies abstractsresultingfromthesearchesindependentlyandresolved
disagreementsbydiscussion.
Electronicsearches
Dataextractionandmanagement
We searched the Cochrane Central Register of Controlled Tri-
We extracted data using methods forms developed by the
als (CENTRAL) 2011, Issue 12, part of The Cochrane Library.
Cochrane Eyes and Vision Group (http://eyes.cochrane.org/
www.thecochranelibrary.com(accessed26January2012),MED-
resources-review-authors).Weextracteddataindependentlyand
LINE(January1950toJanuary2012),EMBASE(January1980
resolveddisagreementsbydiscussion.Oneauthorcutandpasted
toJanuary 2012), OpenGrey(SystemforInformation onGrey
thedatainto RevMan 5(Review Manager 2011)andtheother
Literature in Europe) (www.opengrey.eu/), the metaRegister of
authorcheckedthatthishadbeendonecorrectly.
ControlledTrials(mRCT)(www.controlled-trials.com),Clinical-
Trials.gov (www.clinicaltrials.gov) and the WHO International
Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/
Assessmentofriskofbiasinincludedstudies
search/en). There were no language or date restrictions in the
searchfortrials.Theelectronicdatabaseswerelastsearchedon26 Two authors independently assessed risk of bias using the
January2012. CochraneCollaboration’stoolforassessingriskofbiasasdescribed
See: Appendices for details of search strategies for CENTRAL inChapter8oftheCochraneHandbookforSystematicReviewsof
(Appendix1),MEDLINE(Appendix2),EMBASE(Appendix3), Interventions(Higgins 2011).Weresolveddisagreementsbydis-
OpenGrey(Appendix5),mRCT(Appendix6),ClinicalTrials.gov cussion.Wecontactedtrialauthorsforclarificationonanyparam-
(Appendix7)andtheICTRP(Appendix8). etergradedas’unclear’.Thereviewauthorswerenotmaskedto
Fortheupdatein2012wespecificallylookedforadverseeffects anytrialdetails.
usingasimplesearchaimedtoidentifysystematicreviewsofad-
verseeffectsofvitaminsupplements,seeAppendix(Appendix9)
Measuresoftreatmenteffect
forsearchstrategy.
Ourmeasureoftreatmenteffectwastheriskratiofordichotomous
outcomesandthemeandifferenceforcontinuousoutcomes.Cur-
Searchingotherresources rentlythereviewonlyincludesanalysisofdichotomousoutcomes.
WesearchedtheScienceCitationIndexandthereferencelistsof
reportsoftrialsthatwereselectedforinclusion.Wecontactedthe
Unitofanalysisissues
investigatorsofincludedandexcludedtrialstoaskiftheyknewof
anyotherrelevantpublishedorunpublishedtrials. Theinterventions,bydefinition,areappliedtothepersonbutas
mostpeoplehavetwoeyestrialscananalysedatafromoneorboth
eyes.Thetrialsincludedinthisreviewreportedthedevelopment
ofAMDineithereyeofthepersonthereforetheunitofanalysis
Datacollectionandanalysis
wasthesameastheunitofrandomisation.
Antioxidantvitaminandmineralsupplementsforpreventingage-relatedmaculardegeneration(Review) 5
Copyright©2012TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Assessmentofheterogeneity Theoriginal searchstrategyinvolvedidentifyingalltrialsofan-
Weassessedheterogeneitybyvisualinspectionoftheforestplot, tioxidant interventions and asking trialists if they had collected
theχ2testforheterogeneityandtheI2statistic. dataonAMD.Wewrotetotheauthorsof60trialsofantioxidant
interventions in people with diseases other than AMD. We re-
ceived15responsesandnonehadcollectedanyrelevantdata.All
Datasynthesis 60trialsareshownintheexcludedstudiessectionofthisreview.
Wesummariseddatausingtheriskratio,aftertestingforhetero- Asthisprovedtobeaninefficientwayofidentifyingrelevanttri-
geneitybetweentrialresultsusingastandardChi2test. als,subsequentsearchesincludedtermsforAMD.Threehundred
andsixty-sevenreportsoftrialswerefoundinMay2002,343in
May 2005 and64reportsinJanuary 2006 butnofurthertrials
Subgroupanalysisandinvestigationofheterogeneity
wereidentifiedthatwererelevantforinclusioninthisreview.The
Nosubgroupanalyseswereplanned.Onlyfourtrialsareincluded resultsofthePHSIstudywerepublishedin2007.
atpresentwhichmeansthatitisnotpossibletoinvestigatehet- ThesearcheswererepeatedinAugust2007inwhichatotalof129
erogeneityformally. reportsofstudieswereidentified.TheTrialsSearchCo-ordinator
(TSC)scannedthesearchresultsandremoved84referenceswhich
werenotrelevanttothescopeofthereview.Wescreenedthetitle
Sensitivityanalysis
andabstractsoftheremaining45referencesandobtainedfull-text
Weplannedtoconductsensitivityanalysestodeterminetheim-
copiesoffourreportstoassessforpotentialinclusioninthereview.
pactofstudyqualityoneffectsize.Currentlytherearefourhigh-
WeidentifiedonenewreportfromthePHSIstudytobeincluded
qualitytrialsincludedinthereviewandthereforethisisnotrele-
inthereviewandthethreeremainingstudieswereexcluded.For
vantatpresent.
reasonsofexclusion,see’Characteristicsofexcludedstudies’table.
Anupdate searchwas done inJanuary 2012 whichyielded477
titlesandabstracts. TheTSCscannedthesearchresultsandre-
moved206referenceswhichwerenotrelevanttothescopeofthe
RESULTS review.Wescreenedthetitleandabstractsoftheremaining271
references.Werejected267abstractsasnoteligibleforinclusion
inthereview.Weobtainedfull-textcopiesoffourreportsforfur-
Descriptionofstudies therexamination.OnenewreportfromtheWHSstudyhasbeen
includedinthereviewandthreeotherstudieswereexcluded.For
reasonsofexclusion,see’Characteristicsofexcludedstudies’table.
Resultsofthesearch
Theinitialsearchesresultedin3178titlesandabstracts.Ofthese, Includedstudies
208werereportsofpotentiallyeligibletrialreports.Fromthesere-
Seethe’Characteristicsofincludedstudies’tableformoredetailed
portsweidentifiedsevenprimarypreventiontrialsofantioxidant
information.
vitaminormineralsupplements(ATBC1994;CARET;deKlerk
1998; LINXIAN; Nambour 1995; PHS I; WHS). Investigators
from three trials have confirmed that they did not collect data Typesofparticipants
onAMD(CARET;deKlerk1998;Nambour1995).Thesetrials ThestudiestookplaceinAustralia,USAandFinland.Twostudies
havebeenexcludedfromthereview.Wedidnotreceivearesponse recruited men only (ATBC 1994; PHS I), one study recruited
fromonetrial(LINXIAN)andthistrialhasbeenexcluded.Three women only (WHS) and one study recruited men and women
trialshavepublisheddataonAMDoutcomes(ATBC1994;PHS (VECAT).Peopletakingpartinthetrialswereidentifiedfromthe
I;WHS)andareincludedinthisreview.SearchoftheNational general population. Participants in PHS I were male physicians
EyeInstituteClinicalResearchregisteridentifiedonefurtheron- and in WHS were female health professionals. In ATBC 1994,
goingtrialwhichiscollectinginformationonAMD-theWomen’s arandomsampleof1035menaged65yearsorabovefromthe
AntioxidantCardiovascularStudy(WACS).Therearetwotrials mainstudywereinvitedtoparticipatewitharesponserateof91%
thathaverecruitedparticipantswithandwithoutAMD(AREDS; (941men).InVECAT,18%hadAMDatbaseline.
VECAT).VECATisincludedinthisreviewbecause82%ofpar-
ticipantsdidnothavesignsofAMD.AREDSisnotincludedin
Typesofintervention
thisreviewbecauseAMDoutcomesforpeoplewithoutAMDat
baselinewerenotreported;itisincludedintheCochranereview In ATBC 1994, the groups receivedeither alpha-tocopherol 50
examining the effect of supplementation on progression of the mg per day alone, beta-carotene 20 mg per day alone, alpha-
disease(Evans2006). tocopherol and beta-carotene or placebo. All formulations were
Antioxidantvitaminandmineralsupplementsforpreventingage-relatedmaculardegeneration(Review) 6
Copyright©2012TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
coloured with quinoline yellow. Treatment duration was five to wasgained tocontact theirophthalmologistor optometristand
eightyears(median6.1years).InVECAT,participantswereran- furtherdetailswereobtainedfromthemedicalrecords.
domisedtovitaminE(500IUaday)orplacebo.Supplementation InVECAT,photographsweretakenwithaNidek3-DXfundus
continued for four years. In PHS I, the groups received aspirin camera on Kodachrome 64 ASA colour film. The photographs
325mgeveryotherday,beta-carotene50mgeveryotherday,as- were graded at baseline independently by two trained graders.
pirinandbeta-caroteneorplacebo.Treatmentdurationaveraged EarlyAMD(theprimaryoutcome)wasdefinedassoftdrusen(dis-
12 years. In WHS, participants receivedvitamin E (600 IU on tinctorindistinct)orpigmentarychanges(hyperpigmentationor
alternatedays)orplaceboandwerefollowedupfor10years. hypopigmentation)onphotographicgrading.Onclinicalgrading
thiswaslarge/softdrusenornon-geographicalretinalpigmentep-
itheliumatrophy.VECATusedBailey-Lovievisualacuitycharts
Typesofoutcomemeasures #4and#5(NationalVisionResearchInstitute,Australia).
InATBC 1994,threephotographs ofeach eyeweretaken with
a Canon fundus camera at 40 and 60 degree angles on Kodak Excludedstudies
Ektachrome100ASAslidefilm.Thesephotographsweregraded
Seethe’Characteristicsofexcludedstudies’tableforfurtherin-
byoneobservermaskedtotheparticipant’streatmentgroup.The
formation.
following grades of maculopathy were used: 0 = none; I = dry
maculopathywithharddrusenand/orpigmentarychanges;II=
softmaculardrusen;III=disciformdegeneration;IV=geographic
Riskofbiasinincludedstudies
atrophy.
InPHSIandWHS,AMDwasascertainedbyselfreport:“Have Weconsidered allfour trialstobe atlowrisk ofbias (Figure 1;
youeverhadmaculardegenerationdiagnosedinyourrightorleft Figure 2). See ’Risk of bias’ tables for each included study for
eye?”.Iftheparticipantansweredyestothisquestionpermission detailsoftheassessment.
Figure1. ’Riskofbias’graph:reviewauthors’judgementsabouteachriskofbiasitempresentedas
percentagesacrossallincludedstudies.
Antioxidantvitaminandmineralsupplementsforpreventingage-relatedmaculardegeneration(Review) 7
Copyright©2012TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Figure2. ’Riskofbias’summary:reviewauthors’judgementsabouteachriskofbiasitemforeachincluded
study.
Antioxidantvitaminandmineralsupplementsforpreventingage-relatedmaculardegeneration(Review) 8
Copyright©2012TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.