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AmblyopiaUpdateforthePrimaryCareOD2018

1|P a g e w w w . E y e C o d e B l o g . c o m

ChristopherWolfe,OD,FAAO,Dipl.ABO

AmblyopiaAmblyopiaisaunilateralorbilateralconditionthatcausestheinwhichthebestcorrectedvisualacuity(VA)isworsethan20/20inthepresenceofanormalhealthyeye(nostructuralabnormalitiesoroculardisease)[1].Amblyopiadevelopsduringthecriticalperiod,typicallyinpatients<6-8yearsold(criticalperiod)[2].DependingonthelevelofVAreductiontheprevalencechanges:

• UsingVAof20/40orworse–prevalenceis1.4%ofthepopulation[3]

• UsingVAof20/30orworse–prevalenceis3.5%ofthepopulation[3]

InadditiontoareductioninBCVA,patientswithamblyopiacanalsohave:crowdingeffect,unsteadyfixation,poortracking,reducedcontrastsensitivityandinaccurateaccommodativeresponses[4].

BelowwewillclassifyamblyopiabasedontheconditionthatleadstothereductioninbestcorrectedVA.

FormDeprivationAmblyopiaFormdeprivationamblyopiaoccurswhenthereisanobstructioninthevisualaxisthatprecludesaclearimageontheretina.Commonconditionsthatcanleadtoformdeprivationamblyopiainclude[5][6][7][8]:

• Congenitalcataract(mostcommon)• Traumaticcataract• Cornealopacities• Congenitalptosis

• Vitreousopacification• Prolongeduncontrolledpatching• Prolongedunilateralblepharospasm• Prolongedunilateralatropinization

RefractiveAmblyopiaRefractiveamblyopiaresultsfromablurredimageontheretinainoneorbotheyesthatpreventsthenormaldevelopmentofthevisualpathwayresultinginareductioninVAatthelevelofthevisualcortex[1].

Refractiveamblyopiacanbeclassifiedaseitherisoametropicoranisometropic.

IsoametropicIsoametropicrefractiveamblyopiaoccurswhenthereisanequalbuthighuncorrectedrefractiveerrorinbotheyesthatleadstosignificantretinalblurandreducedVA.

AnisometropicAnisometropicrefractiveamblyopiaoccurswhenthereisanunequaluncorrectedrefractiveerrorbetweenthetwoeyesthatleadstosignificantretinalblurandreducedVA.

CROWDING

Patientsimpactedbythecrowdingeffectwillperformbetterwithlinesoflettersthanblocksoflettersandbetterwithsinglelettersthanlinesofletters.



Typicallyamblyopiaislarger(deeperwithworseVA)forlargerdifferencesinrefractiveerror[9].

AmblyogenicRefractiveErrors[9][10][11][12] Myopia Hyperopia AstigmatismIsoametropic >8.00D >5.00D >2.50D

Anisometropic >3.00D >1.00D >1.50D

TABLE1:COMMONREFRACTIVEAMBLYOGENICRISKFACTORS

HyperopicAnisometropiaSincepatientswithhyperopiawillaccommodatetheleastamountnecessaryatdistanceandneartoseeclearly,lessanisometropiaisrequiredtocauseamblyopiasincethelesshyperopiceyewillbeusedforbothdistanceandnear.MyopicAnisometropiaSincepatientswithmyopiawillusethelessmyopiceyefordistanceandthemoremyopiceyefornearamblyopiawilltendnottooccuruntilthereismorethana3diopterdifferencebetweentheeyes.

StrabismicAmblyopiaStrabismicamblyopiamostcommonlyoccurswhenthereisconstant,unilateralstrabismusduringthecriticalperiod.Sincethereisnobifoveation,eacheyeseesdifferentimages,whichcanleadtoconfusion(centralretina)anddiplopia(peripheralretina).Ifconfusionand/ordiplopialastsforlongenough,thepatientwillactivelysuppressthenon-correspondingretinalimageswhichwillleadtoamblyopia[13].Additionalsensoryadaptationscanoccurtoeliminateconfusionanddiplopia.Theseinclude:

• Eccentricfixation–occurswhenapatientusesanon-fovealpoint(typicallyofthestrabismiceye)whenfixatingmonocularly)[14]

• AnomalousCorrespondence–isabinocularconditionthatlinksanon-fovealpointofthestrabismiceyewiththefoveaofthefixatingeye.

Esotropia(ET)Esotropiaoccurswhentheeyesaretooconvergentfortheobjectofregard.

Congenital/InfantileEsotropia

Congenital(Infantile)esotropiaisaconstantlargeangleesotropiathatoccurspriorto6monthsofage.Additionalclinicalfeaturesthatcanbeseeninclude:

1. Inferiorobliqueoveraction(70%)–thisclinicallysimilarlytoasuperiorobliquepalsy(hyperdeviationduringADduction)

2. Disassociatedverticaldeviation(75%)–elevationofthestrabismiceyewhencovered

INTERMITTENTStrabismuscanbeintermittentoralternatingbutthistypeofstrabismusleadstoamblyopialessfrequentlythanconstantstrabismus.



3. Latentnystagmus(50%)–typicallyahorizontaljerknystagmusthatmanifestswheneithereyeiscovered,thefastphasewillbeAWAYfromthesideoftheoccludedeye[15]

Thelargeangleofthetropiaprecludesbinocularvisionatanydistancesosurgeryisthemostcommoninitialtreatment.

AccommodativeEsotropiaAccommodativeesotropiaoccurswhenthereiseitherahighAC/Aratioorasignificantamountofhyperopia(>+2.00).Theinitialtreatmenttypicallyincludesspectacleprescriptionwithpossiblebifocalwithaddtoneutralizetheneartropia/phoria.

MechanicalEsotropiaMechanicalEsotropiaoccurswhenthereisarestrictionorobstructionofanextraocularmuscle.Causesinclude:

• Extraocularmusclefibrosisinthyroidorbitopathy• Blowoutfracture• Duanesyndrome-iscongenitalandnon-progressiveand

duetoanabsenceofCNVIandaberrantinnervationofabranchofCNIIIintothelateralrectus[16].Additionally,globeretractionoccurswhenboththelateralandmedialrectusarestimulatedatthesametime[17].Thethreetypesinclude[18]:

o Type1(75-80%)-esotropiainprimarygazewithacompensatoryheadturntotheinvolvedside

o Type2(5-10%)-exotropiainprimarygazewithacompensatoryheadturntotheuninvolvedside

o Type3(10-20%)-eitheranesotropiaorexotropiainprimarygaze,andwillhaveacompensatoryheadturntowardstheinvolvedside.Additionally,thereisnoabilitytoadducttheeye

MicroesotropiaMicroesotropiahasanonsetinchildrenunder3yearsandistypicallyaconstant,unilateralesotropiawithanangleoflessthan10∆.Sincetheangleofthetropiaissmall,itcanbechallengingtodiagnosewithacovertest.Patientswithmicroesotropiacanhaveasmallcentralsuppressionscotomathatleadstonorandotstereopsis,additionally,a4baseout(BO)testcanbeutilizedtoaiddiagnosis.

• Inapatientwithnormalfixationandnomicrotropia,wewillseetwodistinctmovementsona4BOtest.Thesemovementsinclude:

1. Versionalmovementofbotheyestowardtheapexoftheprism2. Convergencere-fixationoftheeyethatisnotcoveredbytheprism

• Inapatientwitharightmicroesotropiaandasmallcentralsuppressionscotoma,wewouldexpecttoseethefollowingona4BOtest:

1. Prismplacedoverrighteye–NOmovement2. Prismplacedoverthelefteye–versionalmovementofbotheyestowardtheright,NO

convergencere-fixation

BLOWOUTWetypicallythinkofinferiorrectusentrapmentassociatedwithblowoutfracturesbutwecanalsoseelateralormedialrectusentrapmentsthatleadtoesotropia[29][30].



Exotropia(XT)Exotropiaoccurswhentheeyesaretoodivergentfortheobjectofregard.

CongenitalExotropiaCongenitalexotropiaistypicallyconstantandoccurspriorto6monthsofage.Patientswithcongenitalexotropiahaveanincreasedincidenceof[19]:

• cerebralpalsy• neurologicdisorders• craniofacialdisorders• ocularalbinism

SensoryExotropiaSensoryexotropiaoccursinpatientswithseverelyreducedVAorablindeye.Inpatientswhoaretypicallyolderthan2-4yearsoldiftheybecomeblindorseverelylowvisioncanalsobecomeexotropicduetoaninabilitytodisparateimages[20].

IntermittentExotropiaIntermittentexotropiatypicallyoccurswhenviewingdistanceobjectswhenpatientsaretired,sickorinsomewayataloweredmentalstate(eg.intoxicated)andunderbrightlyilluminatedsituations.The3subtypesofintermittentexotropiaare:

1. BasicIntermittentXT–distanceandnearphoria/tropiameasurementsarewithin10∆ofeachotherandconvergenceisnotimpacted.

2. Pseudo-divergenceexcess–characterizedbyanexotropiathatislargeratdistancebutresolvesafteraperiod(30-60minutes)ofocclusionofthenon-fixatingeye.Thesepatientstypicallycompensatebyincreasingtonicfusionalconvergence.

3. Divergenceexcess–characterizedbyanexotropiathatislargeratdistancethannearbutdoesnotresolveafterocclusionofthenon-fixatingeyeandtypicallyahighAC/Aratio.

DifferentialDiagnosisofAmblyopiaIntheassessmentofpatientswithamblyopiaitisimportanttoconsiderotherconditionsthatcanmasqueradeasrefractiveorstrabismicamblyopia.Someconditionshaveobviousclinicalfindingsandothersaremoresubtle.Theseconditionsinclude[21]:

• Duane’ssyndrome(XT/ET)• CNIIIpalsy(XT)• CNVIpalsy(ET)• Internuclearophthalmoplegia(XT)–affectedeyehaslimitedAdductionand“normaleye”

appearstoexotropicandexhibitsnystagmusonABduction• Orbitalfibrosis/thyroideyedisease(XT/ET)–exotropiceyewillnotmoveinonADductionand

therewillberesistancetoADductiononforcedductiontesting• Moebiussyndrome(XT/ET)–anonprogressivecraniofacialandneurologicaldisorderthat

manifestsasprimarilyasfacialparalysiswithlackoflateraleyemovements• Myastheniagravis(XT/ET)• Achromatopsia



• Coloboma• Myelinatednervefibers• Retinopathyofprematurity• Degenerativemyopia• Hypoplasticopticnerve• Keratoconus• Mediaopacities• Macular,perimacularchorioretinalscar• Macularpathology(e.g.,Stargardt'sdisease)• Opticatrophy• Retrobulbarneuritis• Nystagmus(congenital,latent,manifestlatent)• Craniopharyngioma

TraditionalTreatmentandManagementAsdiscussedabove,therearemanysubsequentsequelaeforthevisualsystemthatcanoccurinpatientswithamblyopia.Traditionaltreatmentoptionsinclude:

1. Refractive error correction 2. Patching 3. Penalization 4. Vision therapy 5. Surgery UpdateontheLiterature–AmblyopiaTreatmentStudies(ATS)Becauseoftheabovevariables,itcanmakedesigningalargestudychallengingtotractimprovementineachoftheareassinceimprovementcouldbemonitoredbasedonVA,binocularvision,accommodativeaccuracy,andevencosmesis.TheadvantageoftheAmblyopiaTreatmentStudiesisthattheyarelargemulti-centerprospectivestudiesthatcanhelpguideusonhowtoimproveVAwithdifferenttreatmentoptionsinpatientswithamblyopia.ThedownsidewiththestudiesisthattheydealalmostexclusivelywithimprovementsinVAandtheyhavehadadifficulttime,duetomanypotentialfactors,evaluatingtheimpactofvisiontherapyandsurgery. ATS-1:Inpatientswithmoderateamblyopiaispatchingorpenalizationmoreeffectiveinpatientsaged3-7yearsold?[22]

• 419childrenwithamblyopia(20/40to20/100)wererandomizedto:o 215patching(6hourstofulltime)o 204atropine(1%QD)

• BaselinemeanVAintheamblyopiceye:20/63• Baselinemeandifferenceinacuitybetweeneyes:4.4lines• VAImprovement:

o SixMonthsMeanVA:§ Patching:20/32§ Atropine:20/32-2



§ Improvementinitiallywasfasterinthepatchinggroup,butaftersixmonths,thedifferenceinacuitybetweentreatmentgroupswassmall

o TwoYearMeanVA:§ Patching:+3.7lines§ Atropine:+3.6lines

ATS-2A:Inpatientswithsevereamblyopiais6hoursofpatchingaseffectiveasfull-timepatchinginpatientsaged3-7yearsold?[23]

• 175childrenwithsevereamblyopia(20/100to20/400)wererandomizedtoeither6hoursperdayorfull-timedailypatching.

• Allpatientswereprescribedatleastonehourperdayofnearvisualactivitieswhilepatching

• VAImprovement:o 6hoursperdayofpatching: +4.8lineso Full-timedailypatching: +4.7lines

ClinicalPearlsATS-1

• Bothtreatmentswerewelltolerated,althoughatropinehadaslightlyhigherdegreeofacceptabilityonaparentalquestionnaire

• At6monthsitisslightlymorelikelyforpatientstakingatropinetohavereducedacuityinthesoundeyeatsixmonthsbutthisdidnotpersistwithfurtherfollowup

• Patchingadvantage:morerapidimprovementinVAandpossiblyaslightlybetteracuityoutcome

• Atropineadvantage:easieradministrationandlowercost• Ifonetreatmentdoesn’tworkconsiderswitchingtotheother• Initialchoiceofpatchingoratropinecanbemadebytheproviderandparent

ClinicalPearlsATS-2A

• Forpatientswithsevereamblyopia,startwith6hoursofpatchingdaily•



ATS-2B:Inpatientswithmoderateamblyopiais2hoursofpatchingaseffectiveas6hoursofpatchinginpatientsaged3-7yearsold?[24]

• 189childrenwithsevereamblyopia(20/40to20/80)wererandomizedtoeither2hoursor6hoursdailypatching.

• Allpatientswereprescribedatleastonehourperdayofnearvisualactivitieswhilepatching

• VAImprovement:o 2hoursperdayofpatching: +2.4lineso 6hoursperdayofpatching: +2.4lines

ATS-2C:Howoftenwillamblyopiaregressaftertreatmentisstopped?[25]• 156children(<8yearsold)withsuccessfullytreated(improvementinVAwithpatchingor

atropine)anisometropicorstrabismicamblyopia8yearsofage,• Followedwithouttreatmentfor52weekstoassessrecurrenceofamblyopia,

o Recurrencedefinedaseither:§ 2ormorelogMARlevelreductionofVAfromenrollment§ Treatmentisrestarted

• Recurrenceo Patientswhowerepenalized: 21%o Patientswhowerepatched: 25%

• Ifpatchingis≥6hoursandNOtaper: 42%• Ifpatchingis≥6hoursandthentaper: 14%

ClinicalPearlsATS-2B

• Forpatientswithmoderateamblyopia,startwith2hoursofpatchingdaily•

ClinicalPearlsATS-2C

• ~1/4ofsuccessfully-treatedamblyopeswillhavearecurrenceinthefirstyearofstoppingtreatment.

• Forpatientstreatedwith6+hoursofdailypatching,theriskofrecurrenceisgreaterwhenpatchingisstoppedabruptlyratherthanwhenitisreducedto2hoursperdaypriortocessation.



ATS-3:Istreatment(patchingorpenalization)effectiveatimprovingVAin7-18yearoldswithamblyopia?[26]

• 507patientswithamblyopia(20/40to20/400)wererandomizedtobetreatedwithspectaclesonlyorspectaclespluspatching/penalization(2-6hours/daydependingonseverity)

• Numberofpatientswhorespondedtoeachtreatmentarmareasfollows:o Patients7to<13yearsold:

§ Spectaclesonly: 25%§ Spectacles+p/p: 53%

o Patients13to<18yearsold:§ Spectaclesonly: 25%§ Spectacles+p/p: 23%

• PatientsPREVIOUSLYtreatedwithp/p: 20%• PatientsNOTPREVIOUSLYtreatedwithp/p: 47%

ATS-4:Isweekendonlyatropineaseffectiveasdailyatropineattreatingpatientswithmoderateamblyopia(20/40to20/80)?[27]

• 168 children (3 to < 7 years old) with moderate amblyopia (strabismus, anisometropia, or mixed) were randomized to be treated with either daily atropine or to weekend atropine

• Improvement in VA of the amblyopic eye from baseline to 4 months averaged 2.3 lines in each group.

• Additionally, VA was either better than 20/25 or better than or equal to the sound eye in: o Daily group: 47% o Weekend group: 53%.

• Stereoacuity outcomes were similar in the two groups. • Patients were more compliant with the daily dosing

ClinicalPearlsATS-3

• Forpatients7to<13yearsold,prescribe2to6hoursperdayofpatching/atropineeveniftheamblyopiahasbeenpreviouslytreated.

• Forpatients13to<18yearsold,prescribe2to6hoursperdayofpatching/atropineifamblyopiahasnotbeenpreviouslytreatedandspectaclesONLYifamblyopiawaspreviouslytreatedwithp/p.

ClinicalPearlsATS-4

• Inpatientswithmoderateamblyipiawhenusingatropine,startwithdailydosingtoimprovecomplianceandthentapertoweekenddosingaftertheinitialfollowup.

•



ATS-5:HowmucheffectdoesspectaclecorrectionhaveonimprovingVAinpatientswithanisometropicamblyopia?[28]

• 84children(3to<7yearsold)withpreviouslyuntreatedanisometropicamblyopia(20/40to20/250)wereevaluatedforimprovementinBCVAafterspectaclecorrectionoftheirametropia

• Amblyopiaimprovedwithspectaclecorrectionaloneby2ormorelinesin77%ofthepatients• Amblyopiaresolvedwithspectaclecorrectionalonein27%ofpatients• StabilizationofVAtookupto30weeksbutaveragedabout6months• Follow-upoccurredevery5weeksuntilstabilization

ATS-6:Whenpatching,does“distance”or“near”activitieshaveanimpactontheresolutionofamblyopia?[29]

• 425children(3to7years)withamblyopia(20/40–20/400)thatwascausedbyanisometropia,strabismus,orboth,andthatpersistedaftertreatmentwithspectacleswererandomizedto2hoursofpatchingperdaywithEITHERnearordistanceactivities.

• VAimprovementat8weekso Distancegroup: averaged2.6lineso Neargroup: averaged2.5lines

• Childrenwithsevereamblyopia(20/100to20/400)improvedbyameanof3.6lineswith2hoursofdailypatching.

ClinicalPearlsATS-5

• Whenstartingtreatmentforanisometropicrefractiveamblyopia,startwithspectaclecorrectionalonethiscanmakepatchingorpenalizationeasier(ifneeded)sincetheamblyopiceyeVAisbetter.

ClinicalPearlsATS-6

• Whenstartingpatchingtreatmentbothdistanceandnearactivitiesareequallyeffective• Encouragepatientstodoactivitiestheyenjoy(iPad,Wii,etc.)• Patientswithsevereamblyopiawillrespondwith2hoursofpatching



ATS-7:HowlongeffectiveisspectaclecorrectionaloneatimprovingVAinpatientswithbilateralrefractiveamblyopiaandwhatisthetimeframeforVAimprovement?[30]

• 113children(age3to<10)withuntreatedbilateralrefractiveamblyopia(20/40to20/320)wereprescribedoptimalspectaclecorrection.

• After1yearoftreatmentVAimprovementwas:o Initialbinocularacuityof20/40to20/80was3.4lineso Initialbinocularacuityof20/100to20/320was6.3lines

• Cumulativeprobabilityofbinocularacuityof20/25orbetterwaso 21%at5weekso 46%at13weekso 59%at26weekso 74%at52weeks

ATS-8:Doesweekendatropinewithaplanolensinthesoundeyehelpimproveamblyopiabetterthanweekendatropinealone?[31]

• 180childrenwithmoderateamblyopia(20/40to20/100)wererandomizedtoweekendatropineplusplanolensoverthesoundeyeorweekendatropineusealone.

• Soundeyehadtobehyperopicof+1.50ormore• VAimprovement

o AtropineONLY: 2.4lineso AtropinePLUS: 2.8lines

• AmblyopiceyeVAof20/25orbettero AtropineONLY: 29%o AtropinePLUS: 40%

• PatientsintheatropineplusgroupweremorelikelytohavereducedVAinthesoundeyeat18weeks,however,thiseffectresolvedafterceasingtreatment.

ClinicalPearlsATS-7

• Within1year3/4ofpatientswithbilateralrefractiveamblyopiawithhavebinocularVAimproveto20/25orbetterwithspectaclecorrectionalone.

ClinicalPearlsATS-8

• AugmentingatropinetreatmentwithaplanolensoverthesoundeyedoesnotsignificantlyimproveamblyopiceyeVA



ATS-9:Ispatchingoratropinemoreeffectiveatimprovingamblyopiainpatientswhoare7to<13?[32]

• 193childrenwithamblyopia(20/40-20/100)wereassignedtoreceiveweekendatropineorpatchingofthesoundeye2hoursperdayandfollowedfor17weeks

• VAimprovement:o Atropine: 7.6letterso Patching: 8.6letters

• VAof20/25orbetter:o Atropine: 17%o Patching: 24%

ATS-10:HoweffectiveareBangerterfiltersoverthesoundeyeatimprovingVAinpatientswithamblyopia?[33]

• 186children(3to<10yearsold)withmoderateamblyopia(20/40-20/80)wererandomizedtoreceive2hoursofdailypatchingoraBangerterfilter(blurtoBVAinamblyopiceye)overthespectaclelensofthesoundeyeandfollowedevery6weeksfor24weeks.

• AverageVAimprovement:o Bangertergroup: 1.9lineso Patchinggroup: 2.3lines

• Percentageofpatientswith3ormorelinesofVAimprovement:o Bangertergroup: 38%o Patchinggroup: 35%

• Percentageofpatientswith20/25VAorbetterinamblyopiceyeacuityo Bangertergroup: 36%o Patchinggroup: 31%,

• TherewasalowertreatmentburdenintheBangertergroup

ClinicalPearlsATS-9

• Treatmentwithatropineorpatchingledtosimilardegreesofimprovementamong7-to<13year-oldswithmoderateamblyopia

• ~20%achievedVAof20/25orbetterintheamblyopiceye

ClinicalPearlsATS-10

• WithasmallaveragedifferenceinVAimprovementbetweenpatchingandBangerterfiltersandlowertreatmentburden,Bangerterfiltertreatmentisareasonabletreatmentoptionforpatientswithmoderateamblyopia.



ATS-13:HowmucheffectdoesspectaclecorrectionhaveonimprovingVAinpatientswithstrabismicorcombinedmechanismamblyopia?[34]

• 146children(3to<7yearsold)withpreviouslyuntreatedstrabismic(S)amblyopia(n=52)orcombined-mechanism(CM)amblyopia(n=94)weretreatedwithspectaclelensesonly

• AverageVAimprovement: 2.6lineso S: 3.2lineso CM: 2.3lines

• VAimprovementof≥2lines: 75%• VAimprovementof≥3lines: 54%• Resolutionofamblyopia: 32%

ATS-15:InpatientswhoseVAplateauedwhenpatchingasperATS-2BhavefurtherimprovedVAifpatchingtimeisincreased?[35]

• 169children(3to<8years)withstableresidualamblyopia(20/32-20/160)after2hoursofdailypatchingforatleast12weekswererandomizedtoeithercontinue2hoursofdailypatchingorincreasepatchingtimetoanaverageof6hours/day.

• AverageVAimprovement:o 2-hourgroup: 0.6lineso 6-hourgroup: 1.2lines

• Percentageofpatientswith2ormorelinesofVAimprovement:o 2-hourgroup: 40%o 6-hourgroup: 18%


• OpticaltreatmentaloneofSandCMamblyopiaresultsinclinicallysignificantimprovementinamblyopiceyeVA

• Amblyopiawillresolvein~33%ofpatientswithSorCMamblyopiawithspectaclesalone• Spectaclecorrectionaloneshouldbestronglyconsideredastheinitialtreatmentfor

patientswithS/orCMamblyopia


• WhenamblyopiceyeVAstopsimprovingwith2hoursofdailypatching,considerincreasingthedailypatchingdosageto6hours



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