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Amblyopia:ThePathophysiology

BehindItandItsTreatment
ByTamaraPetroysan,O.D.

Amblyopia,commonlyreferredtoaslazyeye,affects
24%ofthepopulationandisaleadingcauseofunilateralvision
12
lossintwentytoseventyyearolds. , Amblyopiacausesmore
visionlossthantraumaandoculardisease
combined
inpeople
lessthantwentyyearsold.Despitethis,thereismuch
misinformationaboutthedefinitionofamblyopiaaswellasits
treatment.Herewewillreviewthepathophysiologybehindfunctionalamblyopiaandperforman
uptodate,comprehensiveoverviewoftheAmblyopiaTreatmentStudies(ATS)runbythe
PediatricEyeDiseaseInvestigatorGroup(PEDIG).

Amblyopiaispresentwhenthebestcorrectedvisualacuity(BCVA)cannotreach20/20or
6/6.Itisamostlyunilateral,butsometimesbilateral,decreaseofbestcorrectedvisualacuityinthe
absence
ofanystructuralorpathologicalanomalies.Also,oneormoreofthebelowamblyogenic
factors
must
bepresentbeforetheageofsixtoeightyearstoqualifythevisionlossasfunctional
amblyopia.Thesefactorsinclude(1)aconstant,unilateralesoorexotropia,(2)either
anisometropia,bilateralisometropia,orunilateralorbilateralastigmatismofamblyogenicamount,
3
or(3)someformofstimulusdeprivationorimagedegradation. Theseamblyogenicfactors
preventahealthyvisualpathwayfromformingbetweentheeyeandthebrainduringthecritical
4
periodofneurodevelopment(08yearsold),thusresultinginadecreaseinBCVA. Thevalues
foramblyogenicrefractiveerrorcanbefoundinTable1.Functionalamblyopiaisadiagnosisof
exclusion,soiftheabovementionedtwoconditionsarenotmet,functionalamblyopiacannotbe
diagnosed.Sometimesothercausesforvisionlosssuchaspsychologicalcauses(malingeringand
hysteria)orstructuralandpathologiccauses(nystagmus,opticatrophy,coloboma,
achromatopsia,andkeratoconusamongothers)areincorrectlyclassifiedasamblyopia.
1

Rouse,M.etal.2004.Careofthepatientwithamblyopia.
[
http://www.aoa.org/documents/optometrists/CPG4.pdf
].AccessedJanuary11,2015.
2
M.Khalaj,M.Zeidi,M.Gasemi1,A.Keshtkar.Theeffectofamblyopiaoneducationalactivitiesof
studentsaged915.JBiomedSciEng,4(2011),pp.516521
3
Rouse,M.etal.2004.Careofthepatientwithamblyopia.
[
http://www.aoa.org/documents/optometrists/CPG4.pdf
].AccessedJanuary11,2015.
4

Brown,S.A.,Weih,L.M.,Fu,C.L.,Dimitrov,P.,Taylor,H.R.andMcCarty,C.A.(2000)Prevalenceof
amblyopiaandassociatedrefractiveerrorsinanadultpopulationinVictoria,Australia.Ophthalmic
Epidemiol,7,249259.


5
Table1:AmblyogenicRefractiveErrors
RefractiveError

Isometropia

Anisometropia

Myopia

>8.00D

>3.00D

Hyperopia

>5.00D

>1.00D

Astigmatism

>2.50D

>1.50D

Theintensityofhowvisionisaffectedinamblyopiawilldependonseveralfactorssuchas
ageofonsetaswellastypeandseverityoftheamblyogenicfactor.Mildamblyopiaisclassifiedas
BCVAof20/2520/40,moderateasBCVAof20/4020/100,andsevereasBCVAof
6
20/10020/400. TheaverageBCVAoninitialpresentationis20/50forisometropicamblyopia,
20/60foranisometropicamblyopia,20/74forstrabismicamblyopia,and20/94forcombined
7
anisometropicandstrabismicamblyopia. Ifthebestcorrectedvisiondoesnotgrosslycorrelate
withtheseguidelines,thediagnosisofamblyopiashouldbereevaluatedandothercauses
exploredfurther.

Table2:ClassificationofBCVAinAmblyopia
SeverityofAmblyopia

BCVA

MildAmblyopia

20/2520/40

ModerateAmblyopia

20/4020/100

SevereAmblyopia

20/10020/400

Table3:ExpectedBCVAonInitialPresentation
TypesofAmblyopia

AverageInitialBCVA

Isometropic

20/50

Anisometropia

20/60

Strabismic

20/74

Rouse,M.etal.2004.Careofthepatientwithamblyopia.
[
http://www.aoa.org/documents/optometrists/CPG4.pdf
].AccessedJanuary11,2015.

PediatricEyeDiseaseInvestigatorGroup.Acomparisonofatropineandpatchingtreatmentsformoderate
amblyopiabypatientage,causeofamblyopia,depthofamblyopia,andotherfactors.Ophthalmology
2003110:16328.
7
Rouse,M.etal.2004.Careofthepatientwithamblyopia.
[
http://www.aoa.org/documents/optometrists/CPG4.pdf
].AccessedJanuary11,2015.

CombinedMechanism

20/94

Unilateralamblyopesorindividualswithamilderformofamblyopiamaynotdiscoverthe
presenceofaproblemuntilmuchlaterinlifesincetheunaffectedeyehasseeminglygoodvision.
Asidefromadecreaseinbestcorrectedvisualacuity,amblyopesmaysufferfromanarrayof
8
associateddeficits. Amblyopeswilloftenpresentwithassociatedincreasedsensitivitytocontour
interactionorcrowding,spatialdistortions,impairedstereoacuityandabnormalbinocular
summation,unsteadyandinaccuratemonocularfixation,pooreyetrackingskills,reducedcontrast
9 10
sensitivity,andinaccurateaccommodation. Althoughthesedeficitsaremuchmoreevidentin
11
theaffectedeye,theuninvolvedeyehasbeenshowntoalsobeaffected.
Childrenwith
amblyopiahavebeenshowntoperformpoorlyrelativetotheirnonamblyopiccounterpartsin
12 13
education,employment,sports,andsocioeconomicachievement. Giventhepotentiallackof
symptomsandtheadverseeffectsofamblyopiaonvisualskillsandoveralldevelopmentitis
importantthatachildreceiveacomprehensiveocularandvisualevaluationasearlyinlifeas
possible.TheAmericanOptometricAssociationrecommendsthatchildrengettheirfirsteyeexam
14
between6and12monthsofage.

Certainpopulationsareatincreasedriskforamblyopiadevelopment,makingitthatmuch
moreimportantforthemtoreceiveacomprehensiveeyeexamearlyinlife.Theseinclude
prematureorlowbirthweightbabies,individualswithcerebralpalsyormentalretardation,and
peoplewithafamilyhistoryofhighrefractiveerror,strabismus,amblyopia,orcongenitalcataracts.
15

Rouse,M.etal.2004.Careofthepatientwithamblyopia.
[
http://www.aoa.org/documents/optometrists/CPG4.pdf
].AccessedJanuary11,2015.

PolatU.,MaNaimT.,BelkinM.,SagiD.(2004).Improvingvisioninadultamblyopiabyperceptual
learning.
Proc.Natl.Acad.Sci.U.S.A.
1016692669710.1073/pnas.0401200101
10
SimonisK(2005).
"AmblyopiaCharacterization,Treatment,andProphylaxis"
.SurveyofOphthalmolgy50
(2):123166.
11
SimonisK(2005).
"AmblyopiaCharacterization,Treatment,andProphylaxis"
.SurveyofOphthalmolgy50
(2):123166.
12
Rahi,J.S.,Cumberland,P.M.andPeckham,C.S.(2006)Doesamblyopiaaffecteducational,healthand
socialoutcomes?Findingsfrom1958Britishbirthcohort.BritishJournalofHaematology,33,820825.
13
M.Khalaj,M.Zeidi,M.Gasemi1,A.Keshtkar.Theeffectofamblyopiaoneducationalactivitiesof
studentsaged915.JBiomedSciEng,4(2011),pp.516521
14
AmericanOptometricAssociation.2005.InfantSEE:apublichealthprogramforinfants.
[
http://infantsee.org/x3445.xml
].AccessedDecember27,2014.
15
Rouse,M.etal.2004.Careofthepatientwithamblyopia.
[
http://www.aoa.org/documents/optometrists/CPG4.pdf
].AccessedJanuary11,2015.

Table4:Overviewofamblyopia
DefinitionofFunctionalAmblyopia
BCVAlessthan20/20inoneorbotheyes
Absenceofstructuralorpathologicalcausing
decreaseintheBCVA
Presenceofoneormoreofthefollowing
before68years
Constantunilateralesotropiaor
exotropia
Amblyogenicanisometropia
Amblyogenicbilateralisometropia
Amblyogenicunilateralorbilateral
astigmatism
Stimulusdeprivation
Imagedegradation

PopulationsatIncreased
Risk

Prematurebirth
Lowbirthrate
Cerebralpalsy
Mentalretardation
Familyhistoryof
highrefractive
error,strabismus,
amblyopia,or
congenital
cataracts

DeficitsAssociatedwith
Amblyopia
Increasedsensitivity
tocontourinteraction
/crowding
Spatialdistortions
Impairedstereoacuity
andabnormal
binocularsummation
Unsteadyand
inaccuratemonocular
fixation
Pooreyetracking
Reducedcontrast
sensitivity
Inaccurate
accommodation

Acomprehensiveamblyopiaevaluationshouldincludeadetailedhistoryofthepatients
prenatal,birthanddevelopmentalhistory.Theparentorpatientshouldbequestionedaboutany
evidenteyeturns,habitofclosingoneeye,difficultywithdepth,perceptualdeficits,ordifficultiesin
school.Theocularandvisualexaminationshouldinclude(1)bothamonocularandbinocular
distanceandnearvisualacuityusingawholechart,anisolatedlineandanisolatedletterto
screenforcrowding,(2)adryandwetrefractiontoscreenforlatenthyperopia,(3)analysisof
monocularfixationtoscreenforeccentricfixation,(4)vergence,version,andsensorimotorfusion
toscreenforstrabismus,(5)monocularandbinocularocularmotilitytoscreenforoculomotor
dysfunction,(6)accommodativeamplitudesandfacilitytoscreenforaccommodativedysfunction,
and(7)ocularhealthincludingcolorvisionanddilatedfundusexamtoscreenforoculardiseaseor
anatomicalanomalieswhichmaybethecauseofthedecreasedvisualacuity.Theaverage
expectedvaluesforaccommodationandvergencetestingarelistedinTable5.

1617
Table5:Averageexpectedvaluesforaccommodationandvergencetesting
Test
AverageNormalFinding
DistanceCoverTest(DCT)
orthophoria
NearCoverTest(NCT)
3exophoria
NearPointofConvergence(NPC)
5cm/7cm
RDSStereopsis
20seconds
16

Cooper,Jetal.2010.Careofthepatientwithaccommodativeandvergencedysfunction.
[
https://www.aoa.org/documents/CPG18.pdf
].AccessedJanuary2,2015.
17
Weddell,L.2010.Investigativetechniquesinbinocularvision.
[
http://www.optometry.co.uk/uploads/articles/cetarticle_2611.pdf
].AccessedJanuary20,2015.

DistancePhoria
NearPhoria
DistanceVergenceRanges
NearVergenceRanges
BinocularFusedCrossCylinder
AccommodativeConvergencetoAccommodationRatio(AC/A)
NegativeRelativeAccommodation(NRA)
PositiveRelativeAccommodation(PRA)
AccommodativeAmplitude
AccommodativeFacility
(+/2.00Dlens)
VergenceFacility
(12^BO/3^BI)
Saccades
Pursuit

1exophoria
3exophoria
BaseIn:x/7/4
BaseOut:9/19/10
BaseIn:13/21/13
BaseOut:17/21/11
+0.50
4/1
+2.50
3.00
16(0.25xage)
Monocular:11cpm
Binocular:8cpm
15cpm
SmoothandAccuratewith
slightundershoot
SmoothandAccurate

Tounderstandthepathophysiologyofamblyopiawemustfirstreviewthenormalvisual
pathway.Afteravisualstimulushitstheretina,bothimageformingandnonimageformingvisual
informationtravelsviatheretinalganglioncellsthroughtheopticnervetotheopticchiasmintothe
optictractandendsatthelateralgeniculatenucleus(LGN)ofthethalamus.Themajorityofthe
18
fiberswillthentravelfromtheLGNtotheprimaryvisualcortex(V1)intheoccipitallobe. The
corticallayersaboveandbelowV1consistofcolumnsthatrespondtospecificcharacteristicsof
animage.Theseoculardominancecolumnscompareinputfromthetwoeyes.Eachcolumn
19 20
respondsmoretoinputfromoneeyeoranotherorequallytoboth. Thevisualinputthen
21
leavesthecolumnsandtravelsontootherareasofthevisualcortexforfurtherprocessing.

Atbirth,thefovealconesareabsent.theydevelopoverthefirst24monthsandcontinueto
22
matureintochildhood. Thus,theformationoftheoculardominancecolumnsreliesonboth
18

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1,
HendricksonAE
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23 24

nature(guidancecuesfromretinalganglioncells)andonvisualexperience. Thesesynaptic
connectionsbetweentheeyeandthebrainareeitherstrengthenedbycorrelatedactivityor
weakenedbyuncorrelatedactivity.Oncetheinitialcircuitisformed,thereisacriticalperiodoftime
(upto68yearsoldinhumans)duringwhichoculardominancecolumnscanbemodifiedin
25
responsetovisualexperience. Monoculardeprivationduringthecriticalperiodresultsina
pronounceddecreaseintheareaofV1representingthedeprivedeyeandacorresponding
26 27 28 29
increaseinrepresentationoftheunaffectedeye. Ifthevisualsystemisintroducedto
amblyogenicfactorssuchasvisionblurand/orbinocularvisionsuppression,theywillcausea
progressivereductionofvisualacuity.Thevisionwillcontinuetodeteriorateuntiltheendofthe
30 31 32 33
criticalperiodatwhichtimevisualacuitywillstabilize.

Inisometropicamblyopia,theuncorrectedrefractiveerrorinbotheyescreatesablurred
imageonbothretinas.Overtime,thisvisualblurdisruptsnormalneurophysiologicaldevelopment
ofthevisualpathwayandvisualcortexcausingvisionblurevenwithoptimalvisualcorrection.In
anisometropicamblyopia,theuncorrectedrefractiveerrorinoneeyecreatesablurredimageon
oneretinadisruptingnormalvisualpathwaydevelopmentforthateye.Overtime,thevisual
systemactivelystartstoinhibitorsuppresstheblurredimagecausingcorticalspatialchangesin
theoculardominancecolumnsthatresultinalossofvisualacuity.Instrabismicamblyopia,each
foveareceivesadifferentimage.Abnormalbinocularinhibitionsuppressestheimagefromthe
deviatedeyecausingcorticalspatialchangesthatresultinalossofBCVAaswellaspossible
developmentofeccentricfixationinthedeviatedeye.

Image1:Imagesrepresenting(a)isometropicamblyopia,(b)anisometropicamblyopia,
34
and(c)strabismicamblyopia
23

StellwagenD,ShatzCJ.Aninstructiveroleforretinalwavesinthedevelopmentofretinogeniculate
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1016692669710.1073/pnas.0401200101
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Thegoalofamblyopiatreatmentistoallowtheamblyopiceyetoimproveitsconnection
withthebrainwhiledecreasinginhibitionfromthesoundeye.Thetreatmentisaimedat(a)
decreasingimageblurwhichprovidesinadequatevisualinputfromtheeyetothebrainand
disruptsdevelopmentand(b)atdecreasingbilateralinhibitionsothatthereisequalrepresentation
35 36 37
ofeacheyeintheoculardominancecolumns.

ThePediatricEyeDiseaseInvestigationGroup(PEDIG)isanetworkofoptometristsand
ophthalmologistspracticingineverymodeofpractice.Thegroupwasestablishedin1997to
facilitatemulticenterclinicalresearchinpediatriceyedisease,includingstrabismusandamblyopia.
Thegrouphasperformedextensiveresearchonthesafetyandefficacyofamblyopiatreatmentin
thepediatricandteenagepopulationtitledtheAmblyopiaTreatmentStudies(ATS).Whilethereis
otherresearchavailableonamblyopia,theATSstudiesarelargescale,randomized,controlled,
prospectivestudiesthathaveplayedacriticalroleinrethinkingamblyopiatreatmentandwillbe
reviewedhere.
Ingeneralandunlessstatedotherwise,thesestudieswereperformedonpreviously
untreatedchildren.AcomputerizedsinglesurroundETDRSoptotypewasusedtomeasurevisual
acuityandtheaverageBCVAonentranceintothestudywas20/63intheamblyopiceye.The
majoroutcomeforthestudieswasfinalvisualacuityandbinocularvisualfunctionwasrarely
evaluated.Themajorityofthestudiesperformedincludedchildren3tolessthan7yearsofage.
Thechildrenwereprovidedwiththeiroptimalcycloplegicrefractivecorrectionwhenneededand
thespectacleswereupdatedatthefollowingvisitifachangeinspectacleRxwasnoted.Most
studiesincludedbothmoderate(20/4020/100)andsevere(2010020/400)amblyopes.Weare
goingtogroupthestudiesintoseparatecategoriesasfollows:(a)refractivecorrectionalone,(b)
activetreatment,(c)benefitofnearvisionactivities,(d)recurrenceaftertreatment,(e)treatmentin
olderchildren.

Refractivecorrectionalone

Levi,D.M.,Hariharan,S.&Klein,S.A.(2002)Suppressiveandfacilitatoryspatialinteractionsin
amblyopicvision.VisionRes.42,13791394.
35

36

Tychsen,Lawrence(2012)."Thecauseofinfantilestrabismusliesupstairsinthecerebralcortex,not
downstairsinthebrainstem".ArchivesofOphthalmology130(8):10601061.
37

Shatz,C.J.&Stryker,M.P.(1978)OculardominanceinlayerIVofthecatsvisualcortexandthe
effectsofmonoculardeprivation.JournalofPhysiology281:26783.

ATS5lookedattheeffectofrefractivecorrectionaloneforanisometropicamblyopes.The
38
optimalcycloplegiccorrectionwasprovidedandthechildrenwerefollowedevery5weeks.
SeventysevenpercentofthechildrenimprovedinBCVAby2ormorelineswhile27%ofthe
childrenhadatotalresolutionoftheamblyopiawithBCVAreaching20/20.Themajorityofvision
stabilizationoccurredwithinthefirstfivetofifteenweeksandthechanceofamblyopiaresolution
washigherinthemoderateversustheseveregroup.ATS13evaluatedtheeffectofrefractive
39
correctionaloneonstrabismicandcombinedmechanismamblyopes. Attheendof18weeks,
theamblyopiahadimprovedby2ormorelinesin65%,by3ormorelinesin54%,andfully
resolvedin32%oftheparticipants.Theocularalignmenthadnosignificanteffectonthefinal
improvementinvisualacuity.ATS7lookedatthebenefitofrefractivecorrectionaloneforbilateral
40
refractiveamblyopesage3tolessthan10. Attheendofoneyear,74%ofthechildrenachieved
BCVAof20/25orbetterand60%hada2levelimprovementontheRandotpreschool
stereoacuitytest.

Thesethreestudiesshowthatopticaltreatmentaloneprovidesasignificantimprovement
invisualacuityandsometimesatotalresolutioninamblyopiaofvariousetiology.Optimaloptical
correctionwithfrequentfollowupsandupdatestospectacleRxshouldbetriedasaninitiallineof
treatmentforamblyopia.Ifthespectaclesalonedonotresolvetheamblyopia,thentheimproved
amblyopicBCVAmayleadtobettersuccessandcompliancewithfurthertherapysuchas
patching.

Activetreatment

Thegoalofpenalizingthevisioninthenonamblyopiceyeistoeitheroccludethevisionof
thateyefullyorincreasetheblurofthateyebeyondthatofthebluroftheamblyopiceyetoallow
normalneurodevelopmentbetweentheamblyopiceyeandbrain.Stickonocclusivepatchesthat
coverthewholeeyearepreferablesincethechildcannotpeakaboveorbelowtheeyepatchand
occlusionisguaranteed.Bangerterfiltersaretransparentstickongradedfoilsthatadhereto
glassesandmodulatethedegreeofblurbyproducingdiffuseimagedefocusatalldistances.
Atropineproducesaparesisoftheaccommodativesystemthusdecreasingvisualacuity.The
degreeofvisionblurwithatropinedependsontheinitialrefraction,ifthechildiswearingglasses,
andhowcloseanobjectis.Theclosertheworkingdistance,themoreblurisproducedsince
accommodationisnotpresenttocleartheimage.Atropineisbestusedinhyperopicchildrensince
myopicchildrencansimplyremovetheirglassesandfocustheimageonthenonamblyopiceye
withoutaccommodativeeffort.

38

PediatricEyeDiseaseInvestigatorGroup.Treatmentofanisometropicamblyopiainchildrenwith
refractivecorrection.Ophthalmology2006113:895903.
39
PediatricEyeDiseaseInvestigatorGroup.OpticalTreatmentofStrabismicandCombined
StrabismicAnisometropicAmblyopia.Ophthalmology.2011Sep28.
40
PediatricEyeDiseaseInvestigatorGroup.Treatmentofbilateralrefractiveamblyopiainchildrenthreeto
lessthan10yearsofage.AmJOphthalmol2007144:48796.

ATS1studiedtheeffectof1%dailyatropinedropsversus6hoursofpatchingfor
41
treatmentofmoderateamblyopia. After6months,79%ofthepatchingand74%oftheatropine
grouphadimprovedby3ormorelinesorhadaBCVAofbetterthan20/32.Attheendof2years,
thisincreasedto86%forthepatchingand83%fortheatropinegroupwithameanvisualacuityof
20/32+inbothgroups.AyoungerageattreatmentinitiationwasassociatedwithabetterBCVA
outcomeandtheatropinegroupreportedagreatercompliancewithtreatment.ATS2bcompared
42
patching2versus6hoursformoderateamblyopia. After4months,bothgroupshadamean
improvementof2.4linesinBCVAwiththe2hourgroupreportingbettercompliance.ATS2a
43
compared6hoursversusfulldaypatchingforsevereamblyopia. After4months,bothgroups
againhadanequalimprovementinBCVAof4.8lineswithlesspatchinghavingahigher
compliancerate.ATS4compareddailyatropineusetoweekendonlyuseonlyformoderate
44
hyperopicamblyopia. After4months,bothgroupsimprovedbyanaverageof2.3lines.ATS10
evaluatedtheeffectofBangerterfiltersversus2hoursofpatchingfor3tolessthan10yearolds.
45
Thevisionwasfirststabilizedwithcycloplegicrefractionandafter24weeksaverage
improvementwas2.3linesinthepatchinggroupand1.9linesinthefiltergroup.

ThesecondportionATS5lookedatthebenefitofpatching2hoursadayformoderate
andsevereanisometropicandstrabismicamblyopiaafterfirststabilizingtheBCVAwith
46
spectacles. AfterstabilizingtheBCVAwithanoptimalcycloplegicRx(usually16weeks),the
treatmentgroupwaspatchedfor2hoursperdaywithanhourofnearactivitiesversusspectacle
Rxalonewithanhourofnearvisionactivities.After5weeks,thepatchinggroupimprovedbyan
extra2.2linesversusthecontrolgroupwhichimprovedby1.3lines.ATS15evaluatedthe
effectivenessofincreasingdailypatchingfrom2to6hoursinchildrenwithstableresidual
47
amblyopia(20/3220/160)afterpreviouslyundergoingpatchingfor2hours/day .Aftertenweeks,
theaverageBCVAinthetreatmentgroupimprovedby1.2linesversus0.50linesinthecontrol
group.Fortypercentofthetreatmentgroupimprovedby2ormorelinesversus18%ofthe
control.ATS8evaluatedatropineplusopticalpenalizationfortreatingmoderatehyperopic
amblyopes.AfterBCVAstabilizationwithspecs,bothgroupsreceivedweekendatropineinthe
nonamblyopiceye.Thetreatmentgroupreceivedglasseswithaplanodistancelensfortheir
nonamblyopiceye,effectivelyblurringthematalldistances.Thecontrolreceivedtheirproper
41

PediatricEyeDiseaseInvestigatorGroup.Arandomizedtrialofatropinevspatchingfortreatmentof
moderateamblyopiainchildren.ArchOphthalmol2002120:26878.
42
PediatricEyeDiseaseInvestigatorGroup.Arandomizedtrialofpatchingregimensfortreatmentof
moderateamblyopiainchildren.ArchOphthalmol2003121:60311.
43
PediatricEyeDiseaseInvestigatorGroup.Arandomizedtrialofpatchingregimensfortreatmentof
severeamblyopiainchildren.Ophthalmology2003110:207587.
44
PediatricEyeDiseaseInvestigatorGroup.Arandomizedtrialofatropineregimensfortreatmentof
moderateamblyopiainchildren.Ophthalmology2004111:207685.
45
PediatricEyeDiseaseInvestigatorGroup.ArandomizedtrialcomparingBangerterfiltersandpatchingfor
thetreatmentofmoderateamblyopiainchildren.Ophthalmology2010117(5):9981004.
46
PediatricEyeDiseaseInvestigatorGroup.Arandomizedtrialtoevaluate2hoursofdailypatchingfor
strabismicandanisometropicamblyopiainchildren.Ophthalmology2006113:90412.
47

PediatricEyeDiseaseInvestigatorGroup.Arandomizedtrialofincreasingpatchingforamblyopia.
Ophthalmology2013Nov120(11):22707.Epub2013Jun4

visioncorrectionfordistance,leavingthemblurredonlyatnear.Attheendof18weeks,the
treatmentgroupimprovedby2.8linesversus2.4linesinthecontrolgroup.

Thesepenalizationstudiesshowthatbothpatchingandatropine,andtoaslightlylesser
effectBangerterfilters,areeffectiveoptionsfortreatingamblyopia.Optimalimprovementcanbe
madeiftheBCVAisfirststabilizedviarefractivecorrectionandthenpenalizationisinitiatedfor
residualvisualacuitydeficits.Ifthereisresidualamblyopiaaftertheactivetreatmentregimen,an
increaseinpatchingtimeoraddingopticalpenalizationtoatropinemayprovidefurther
improvementinBCVA.

Benefitofnearactivities

ATS6evaluatedthebenefitofprescribingcommon,athomenearactivitiesduring
patchingregimenstoenhanceimprovementinvisualacuity.AfterBCVAstabilizationwithspecs
thechildrenwerepatched2hours/dayathomeandperformedeithercommoneyehand
coordinationactivitiesatnearoreitheractivities6feetawayoroutdoorplay.Attheendof8
weeks,boththedistanceandnearactivitygroupsimprovedby2.5lines.Theresultswere
statisticallysimilarat17weeks.Whilerefractivecorrectionandpenalizationmayimprovethe
BCVA,theydonotprovidetreatmentforallaspectsofvisionimpactedbyamblyopia,including
binocularity.

Astudyevaluatingdoctorsupervisedvisiontrainingwouldberecommendedtofurther
evaluatedthebenefitofvisiontherapyforamblyopiatreatment.ATS12,astudyterminatedin
2009duetolackofsubjectparticipation,wastolookattheeffectivenessofpatchingwithactive
visiontherapyversuspatchingwithcontrolvisiontherapy.ATS18startedrecruitingin2014to
comparetheeffectivenessof1hour/dayofbinoculargameplaywith2hours/dayofpatchingin
48
children5to<13yearsofage.

Recurrenceaftertreatment

ATS2cevaluatedtherecurrenceofamblyopiainpreviouslysuccessfullytreatedpatients.
Thechildrenweretreatedwitheitheratropineorpatchingandthendiscontinuedtreatmentand
monitored.Attheendofoneyear,76%hadnodecreaseinBCVAwhile24%hada2ormoreline
lossinBCVA.ThedecreaseinBCVAwasequalinboththepatchingandatropinegroups.For
subjectspatched6to8hours/day,therecurrencewasincreasedto42%ifthetreatmentwas
abruptlydiscontinued.Ifthetreatmentwasfirstdecreasedto2hours/dayforseveralweeksand
thendiscontinued,thechanceofrecurrencedecreasedto14%.Inthegroupthathadrecurrence,

48

PediatricEyeDiseaseInvestigatorGroup.2015.Studyofbinocularcomputeractivitiesfortreatmentof
amblyopia.[
http://pedig.jaeb.org/Studies.aspx?RecID=235
].AccessedJanuary20,2015

76%occurredwithinthefirst3to6months.Neitherocularalignmentnorlevelofstereoacuity
wereprotectivefactorsagainstrecurrence.

Treatmentinolderchildren

ATS9comparedvisionstabilizationwithspectaclesfollowedbyweekendatropineversus
2hoursofpatchingformoderateamblyopesage7to12.After17weeks,thevisualacuity
improvedby7.6lettersintheatropinegroupand8.6lettersinthepatchinggroup.ATS3
evaluatedthebenefitofamblyopiatreatmentforchildren718.Thecontrolgroupreceivedoptimal
refractivecorrectiononlywhilethestudygroupreceivedrefractivecorrectionpluseitherpatching
(2to6hours)orweekendatropine.Apositiveresponsewasconsideredanimprovementof2
linesinBCVAafter24weeks.Inthe712yeargroup,53%ofthetreatmentand25%ofthe
glassesgrouphadapositiveresponse.Inthe1317yeargroup,25%ofthetreatmentand23%of
theglassesgrouphadapositiveresponse.Iftheteenagegroupwasfurtherevaluated,inchildren
whohadnoprevioustreatment,47%ofthetreatmentand20%oftheopticalonlygroupshoweda
positiveresponse.Thestudythenwentontheevaluatethechanceofrecurrenceafterayear
withouttreatmentwhereonly5%ofthepatientshadadecreaseinBCVAof2ormorelines.

Thesestudiesshowthatachildsageisnotalimitingfactorforamblyopiatreatment.This
islikelyduetotheneuroplasticityofthebrain.Treatmentshouldbeinitiatedinolderchildren,
especiallyiftheyhaveneverreceivedprevioustreatment.Furtherwellcontrolled,prospective
studiesareneededtoevaluatethebenefitofamblyopiatreatmentinadults.

Table6:OverviewofAmblyopiaTreatmentStudies

StudyNumber

StudyGoal

StudyOutcomes

ATS5

effectofrefractivecorrection
aloneforanisometropic
amblyopes

77%ofthechildren
improvedinBCVAby2or
morelines
27%ofthechildrenhada
totalresolution
themajorityofvision
stabilizationoccurredwithin
thefirst515weeks
thechanceofamblyopia
resolutionwashigherinthe
moderatevs.severegroup

ATS13

effectofrefractivecorrection
aloneonstrabismicand
combinedmechanism
amblyopes

amblyopiaimprovedby2or
morelinesin65%,by3or
morelinesin54%,andfully
resolvedin32%

ocularalignmenthadno
significanteffectonthefinal
improvementinvisualacuity

ATS7

benefitofrefractivecorrection
aloneforbilateralrefractive
amblyopes

74%achievedBCVAof
20/25orbetter
60%hada2level
improvementontheRandot
preschoolstereoacuitytest

ATS1

effectof1%dailyatropine
dropsversus6hoursof
patchingfortreatmentof
moderateamblyopia

after6months,79%ofthe
patchingand74%ofthe
atropinegrouphadimproved
by3ormorelinesorhada
BCVAofbetterthan20/32.
after2years,thisincreased
to86%ofthepatchingand
83%oftheatropinegroup
hadimprovedby3ormore
linesorhadaBCVAofbetter
than20/32
ayoungerageattreatment
initiationwasassociatedwith
abetterBCVAoutcome
Atropinegroupreported
greatercompliancewith
treatment

ATS2b

comparedpatching2versus6 at4months,bothgroups
hoursformoderateamblyopia hadameanimprovementof
2.4linesinBCVA
2hourgroupreportedbetter
compliance

ATS2a

compared6hoursversusfull
daypatchingforsevere
amblyopia

at4months,bothgroups
hadameanimprovementin
BCVAof4.8lines
6hourgroupreported
bettercompliance

ATS4

compareddailyatropineuse
toweekendonlyuseonlyfor

at4months,bothgroups
improvedbyanaverageof
2.3lines

moderatehyperopic
amblyopia

ATS10

effectofBangerterfilters
versus2hoursofpatching

after24weeksofBCVA
stabilizationwithoptical
correction,average
improvementof2.3linesin
thepatchinggroupand1.9
linesinthefiltergroup

ATS5(secondportion)

benefitofpatching2hoursa
dayformoderateandsevere
anisometropicandstrabismic
amblyopia

after16weeksofBCVA
stabilizationwithoptical
correctionthepatchinggroup
improvedbyanextra2.2lines
versusspectacleonlygroup
whichimprovedby1.3lines

ATS15

evaluatedtheeffectivenessof
increasingdailypatchingfrom
2to6hoursinchildrenwith
stableresidualamblyopia

aftertenweeks,theaverage
BCVAinthetreatmentgroup
improvedby1.2linesversus
0.50linesinthecontrolgroup
40%ofthetreatmentgroup
improvedby2ormorelines
versus18%ofthecontrol

ATS8

evaluatedatropineplusoptical
penalizationfortreating
moderatehyperopic
amblyopes

attheendof18weeks,the
treatmentgroupimprovedby
2.8linesversus2.4linesin
thecontrolgroup

ATS6

benefitofprescribing
common,athomenear
activitiesduringpatching
regimenstoenhance
improvementinvisualacuity

attheendof8weeks,both
thedistanceandnearactivity
groupsimprovedby2.5lines

ATS2c

evaluatedtherecurrenceof
amblyopiainpreviously
successfullytreatedpatients

attheendofoneyear,76%
hadnodecreaseinBCVA
while24%hada2ormore
lineloss
thedecreaseinBCVAwas
equalinboththepatchingand
atropinegroups

forthegrouppatched6to8
hours/day,therecurrence
wasincreasedto42%ifthe
treatmentwasabruptly
discontinued.Ifthetreatment
wasfirstdecreasedto2
hours/dayforseveralweeks
andthendiscontinued,the
chanceofrecurrence
decreasedto14%
inthegroupthathad
recurrence,76%occurred
withinthefirst3to6months.
neitherocularalignmentnor
levelofstereoacuitywere
protectivefactorsagainst
recurrence

ATS9

comparedvisionstabilization
withspectaclesfollowedby
weekendatropineversus2
hoursofpatchingfor
moderateamblyopesage
712

after17weeks,thevisual
acuityimprovedby7.6letters
intheatropinegroupand8.6
lettersinthepatchinggroup

ATS3

evaluatedthebenefitofactive inthe712yeargroup,53%
amblyopiatreatmentfor
ofthetreatmentand25%of
children718
theglassesgrouphada
positiveresponse
inthe1317yeargroup,
25%ofthetreatmentand
23%oftheglassesgrouphad
apositiveresponse
inchildrenwhohadno
previoustreatment,47%of
thetreatmentand20%ofthe
opticalonlygroupshoweda
positiveresponse
5%ofthepatientshada
decreaseinBCVAof2or
morelinesafteroneyearof
notreatment

Inconclusion,amblyopiaisadiagnosisofexclusionandhasstrictguidelineswhichshould
befollowedwhenmakingthediagnosis.Whenconsideringinitiatingamblyopiatreatment,itis
importanttoincludetheparentand/orpatientinthedecisionmakingprocess.Alltreatment
options,includingtheirrisks,benefits,andalternatives,andexpectationsshouldbediscussedand
atreatmentplanthatbestfitseachindividualpatientshouldbeformulated.Whileearly
interventionisideal,withappropriatemanagementandtreatmentamblyopiapatientsarelikely
obtainasuccessfuloutcome,andpossiblyfullresolution,nomattertheirage.Patientsshouldbe
monitoredcloselyandfrequentlyduringandafteramblyopiatreatmenttoallowfortreatment
modificationasneededandtowatchforamblyopiarecurrence.Whileopticalcorrectionalonecan
resolveamblyopia,activetreatmentthroughpenalizationorcombiningdifferenttreatmentmethods
canfurtherimprovevisualacuityinresidualamblyopia.Furtherstudiesareneededtoevaluatethe
benefitofactiveinofficeorhomevisiontrainingforamblyopiatreatmentaswellasitsassociated
deficits.

____________________________________________________________________________

AboutourAuthor

Dr.TamaraPetrosyangraduatedwithhonorsfromtheStateUniversityofNewYork(SUNY)
CollegeofOptometryin2009andwentontodoaresidencyinvisionrehabilitation,headtrauma,
lowvision,andoculardiseaseattheNorthportVAMedicalCenter.In2011shejoinedthefaculty
attheSUNYCollegeofOptometrywhereshepreceptsthirdandfourthyearinternsintheprimary
care,adultswithdisabilities,andpediatricunits.Dr.Petrosyanalsosupervisesprimarycareand
oculardiseaseinternsandresidentsattheEastNewYorkDiagnosticandTreatmentCenterin
Brooklyn,NY.From20122014Dr.PetrosyanwasonstaffattheRefuahHealthCenterwhere
sheperformeddirectcarepediatricandadultexamsandvisiontherapytraining.Dr.Petrosyanis
currentlyontheboardofdirectorsfortheNewJerseySocietyofOptometricPhysicians(NJSOP)
andisthechairofboththevisiontherapyandinfantvisionclinicalcarecommitteesofNJSOP.
SheisalsothecoordinatoroftheNJSOPYoungO.D.programandhashelpeddevelopNJSOP
mentorshipprogram.Dr.Petrosyanistherecipientofthe2013NJSOPChairpersonoftheYear
Award,2014NJSOPYoungO.D.oftheYearAward,2015AOAYoungO.D.oftheYearAward,
andthe2015NJSOPOptometricJournalismAward.ShelivesinNewJerseywithherhusband
andthreechildren.

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Copyright
2016byTheAmericanOptometricAssociation