Professional Documents
Culture Documents
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
Sundsten,JohnW.Nolte,John(2001).Thehumanbrain:anintroductiontoitsfunctionalanatomy.St.
Louis:Mosby.pp.410447.
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OCLC
47892833
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AdamsDL
1,
SincichLC
,
HortonJC
.Completepatternofoculardominancecolumnsinhumanprimary
visualcortex.
JNeurosci.
2007Sep2627(39):10391403.
20
Huberman,A.D.etal.(2008)Mechanismsunderlyingdevelopmentofvisualmapsandreceptivefields.
AnnuRev.Neurosci.31,479509
21
VanEssenDC,AndersonCH,FellemanDJ.Informationprocessingintheprimatevisualsystem:an
integratedsystemsperspective.Science255:419423,1992.
22
VajzovicL
1,
HendricksonAE
.Maturationofthehumanfovea:correlationofspectraldomainoptical
coherencetomographyfindingswithhistology.
AmJOphthalmol.
2012Nov154(5):779789.e2.doi:
10.1016/j.ajo.2012.05.004.Epub2012Aug13.
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
connectivity.Neuron33:357367,2002.
24
Shatz,C.J.&Stryker,M.P.(1978)OculardominanceinlayerIVofthecatsvisualcortexandthe
effectsofmonoculardeprivation.JournalofPhysiology281:26783.
25
StrykerMP,HarrisWA.1986.Binocularimpulseblockadepreventstheformationofoculardominance
columnsincatvisualcortex.J.Neurosci.6:211733
26
Shatz,C.J.&Stryker,M.P.(1978)OculardominanceinlayerIVofthecatsvisualcortexandthe
effectsofmonoculardeprivation.JournalofPhysiology281:26783.
27
CrowleyJ.C.andKatzL.C.(2000)Earlydevelopmentofoculardominancecolumns.Science,290:1321
1324.
28
StellwagenD,ShatzCJ.Aninstructiveroleforretinalwavesinthedevelopmentofretinogeniculate
connectivity.Neuron33:357367,2002.
29
Shatz,C.J.&Stryker,M.P.(1978)OculardominanceinlayerIVofthecatsvisualcortexandthe
effectsofmonoculardeprivation.JournalofPhysiology281:26783.
30
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31
PolatU.,MaNaimT.,BelkinM.,SagiD.(2004).Improvingvisioninadultamblyopiabyperceptual
learning.
Proc.Natl.Acad.Sci.U.S.A.
1016692669710.1073/pnas.0401200101
32
Levi,D.M.(2006)."Visualprocessinginamblyopia:humanstudies".Strabismus14(1):1119.
33
Huberman,A.D.etal.(2008)Mechanismsunderlyingdevelopmentofvisualmapsandreceptivefields.
AnnuRev.Neurosci.31,479509
34
NASA.1993.HubbleimagesofM100beforeandaftermirrorrepair.
[
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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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writtenpermissionofthepublisher.
Copyright
2016byTheAmericanOptometricAssociation