BritishJournal ofOphthalmology, 1991,75, 111-116

Anisometropic and strabismic amblyopia in the agegroup 2 years and above: a prospective study of theresults of treatment

Joan Lithander, Johan Sjostrand

AbstractForty-four children aged 2-9 years withstrabismic and anisometropic amblyopia wereprospectively followed up during amblyopiatreatment. The efficacy ofoptimised treatmentin terms of number of cured children, time toachieve cure, and rate of initial improvementofvisual acuity was evaluated in relation to ageat start of treatment, type and initial degree ofamblyopia, and adherence to treatmentregimen. Compliance with treatment was themost critical factor predicting a successfuloutcome. Among the compliant children 35 outof 36 were cured (visual acuity differencebetween amblyopic and non-amblyopic eyesnot more than one line) within five monthsregardless of age, treatment regimen, and typeor initial degree of amblyopia as comparedwith none in the group with low compliance.Most of these compliant children were curedwithin three months, with shorter treatmenttimes on average for the younger children.The initial improvement of visual acuity wasalso faster at 2 years than at 4 years of age.Anisometropes with moderate amblyopia atthe start oftreatment were over-represented inthe group with low compliance. We concludethat early diagnosis of strabismus in com-bination with general population screening atthe age of 4 to detect amblyopia caused byanisometropia or microstrabismus seems to beefficacious for the cure of most cases. Themajor factor in treatment failure was found tobe inadequate adherence to the treatmentreginen.

Department ofOphthalmology,University ofGoteborg,SwedenJ LithanderJ SjostrandCorrespondence to:Joan Lithander, MD,Department ofOphthalmology, University ofGoteborg, Sahlgren'sHospital, S-413 45 Goteborg,Sweden.Accepted for publication6 September 1990

At 4 years of age the Swedish population isscreened for subnormal vision. One major aim isto detect amblyopia by measuring visual acuity atthe child health centres. Nordlow andJoachimsson' and Kohler and Stigmari3 initiatedthis programme and found it efficacious.The questions we asked were: Could anything

be gained by lowering the screening age? Isearlier treatment more effective and associatedwith a better outcome? Few systematic studieshave evaluated the effect of factors such as agebelow 4 and type and degree of amblyopia in thetreatment of the clinically most common formsofamblyopia, that is, those caused by strabismusor anisometropia.45Most clinicians agree that treatment of

amblyopia is less favourable if it appears duringthe first months of life and if it is associated withextreme degrees of anisometropia.6 But therelative importance of various factors for itssuccessful treatment in the more usual clinical

situation is not well defined. The efficacy ofscreening for the treatment ofamblyopia has alsobeen questioned during recent years.`9The recent development of accurate methods

for testing visual acuity with optotypes inyounger children down to an approximate age of2 years'0 (Lithander, in preparation) has enabledus to study the efficacy ofamblyopia treatment asrelated to optotype acuity over an extended timeperiod. At the same time more interest has beenfocused on the psychological implications ofamblyopia treatment in an active child, and lowcompliance has been considered to be a majorreason for treatment failure in older children.5

In this prospective clinical study of childrenaged 2 years or more we have evaluated theassociation of various factors such as age at startof treatment and initial degree or type ofamblyopia with efficacy of amblyopia treatment.Furthermore, we have analysed factors ofimportance for the successful outcome ofamblyopia therapy.

Patients and methods

PATIENTSForty four children aged 2 to 9 years withunilateral amblyopia diagnosed by the firstauthor during the time period 1983-7 at thePaediatric Ophthalmology Unit of OstraHospital, Goteborg, and fulfilling the inclusioncriteria were enrolled consecutively in the study.Inclusion criteria were previously untreatedunilateral amblyopia due to strabismus (n=27),or anisometropia without strabismus (n= 17),persisting after eight or more weeks of spectaclewear ifoptical correction was needed. All patientswith large angle strabismus, microstrabismus, orstrabismus in combination with anisometropiawere classified as strabismus. Amblyopia wasdefined as a difference of at least two lines on theacuity chart between the eyes when tested withbest correction after eight weeks with spectacleswhen needed.They were mainly referred from the child

health centres of Goteborg at any age below 7years either for squinting problems or for sub-normal vision detected at the visual acuityscreening test at the age of 4. There were 22 boysand 22 girls. All the children were followed upfor at least three years following the start oftreatment (mean follow-up time 4 5 years).

CLINICAL EXAMINATIONAfter retinoscopy optical correction was pre-scribed when needed for full time use. Aniso-

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...-..........................-..

Figure I Design principles of thze 0 test, the Kolt test, and HYOT test.

metropia was defined as the difference of onedioptre or more in any symmetrical meridian.The clinical characteristics of the children aresummarised in Table 1.

Visual acuity (VA) was assessed at the age 2 to21½2 years with the 0-test (Lithander, in pre-paration). The 0-test is a new method designedfor testing visual at the age of 18 months andabove. It has a testing distance of 40 cm. Thechild has to point out the 0 among six symbols,for instance HVTOVH. The 0 is shown indifferent positions. It tests visual acuity forsingle symbols as the interspace between theletters is large. As soon as the child understoodthe matching symbol principle, the Kolt testwith four alternative optotypes (triangle, square,circle, and cross) was used'0 (Lithander, inpreparation). The testing distance is 3 m. Thechildren have a matching box with the symbolson four buttons. They have to press the buttoncorresponding to the optotype indicated at thetest chart. As reinforcement a melody is played ifthey perform correctly. The 0 test, the Kolt test,and the HVOT test are shown in Figure 1. At theage of 4 the HVOT' was the elected test. For allthe tests above the acuity was tested in approxi-mately logarithmic steps from 0 05 or 0-1 to 1-0.The visual acuity was defined as the line at which3/4 of the optotypes were correctly identified. Incases with VA below 0-1 the testing distance wasdecreased appropriately and the valuestransformed.

After the age of 5 visual acuity was tested withSnellen's E chart, and at near Haase's C test with2-6 arc minutes of interspace between the opto-types.'2 Snellen's letter chart was used, in general,after 7 years of age.

TREATMENTThe primary treatment in all cases was patchingon the skin in front of the good eye. The timeperiod for repeated occlusion was selectedaccording to age. Thus a 2-year-old was treatedwith two days of occlusion and one free day; a 5-year-old child was patched five days and had one

free. Sixteen out of 27 children with strabismus(63%) and 10 out of 17 anisometropes (59%) hadno other treatment (except glasses) than patchingon the skin until cure. If the child refused or wasunable to wear a patch on the skin the secondchoice of treatment was instillation of atropine inthe best eye, if the acuity of the amblyopic eyewas above 0-2. In these cases 0-5% atropine wasinstilled daily for one week followed by one weekwithout treatment, and the treatment cycle wasrepeated until cure. When the residual amblyopiawas mild and problem with the patchingoccurred, another choice of treatment was aRyser filter attached to the glass of the good eye.

In order to monitor rate ofimprovement, timeuntil first cure, and to optimise compliance thechildren were examined so far as possible everyweek during the first four weeks and then everysecond week for the following four weeks. Afterthe start of the third month of follow-upexaminations were carried out once a monthuntil cure - that is when one line VA difference orless between the two eyes was achieved. Afterthat, treatment was continued on a part timebasis (occlusion of the good eye for one or twohours daily), preferably at children's TV time,until the acuity was equal in both eyes. Anexception was in cases of microstrabismus. Inthis group the endpoint for treatment was oneline of acuity difference between the eyes inorder to avoid diplopia.

COMPLIANCEA great effort was made to obtain optimalcompliance with treatment. Any problems witheither glasses, patching, atropine, Ryser filter, orfollow-up were recorded. Low compliance wasnoted if the prescribed glasses were not worn, ifappointments were missed more than once, andif atropine or the Ryser filter was not properlyused after a period with problems with patching.Compliance was carefully controlled, as we metthe family weekly at the beginning. Detailedinformation and instructions to the parents andthe children before and during treatment were

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Anisometropic and strabismic amblyopia in the agegroup 2years and above: a prospective study ofthe results oftreatment

Table I Clinical characteristics: grade ofamblyopia andcompliance (c) 120-

Number ofcases

Grade ofamblyopia Anisometropia Strabimus(VA at start)

good c lov c good c low c

<0 1 - - 6 101-0-3 3 5 15 204-0 8 9 - 3 -

Total 12 5 24 3

regarded as essential. The same ophthalmologist(JL) and nurse were responsible for the examina-tions and for giving information to the parents.

ResultsThe adherence ofthe 44 children to theamblyopiatherapy was graded. Thirty six of the childrenhad good compliance to any form of amblyopictreatment (82%) whereas eight children had lowcompliance (Table 1).Of the 36 children with good compliance to

any form oftreatment 35 were cured according toour definition (one line of acuity differencebetween the eyes) regardless oftype ofamblyopiaor grade of initial amblyopia in the age group 2 to7 years. The only 'failure' in this group was a 6-year-old girl with a high degree of anisometropia(retinoscopy right eye +2 5 sph, left eye -6 0sph -cyl 4-0 ax O) combined with a monolateralesotropia. She improved from 0 05 to 04 in 90days, after which no further improvement waspossible in spite of optimal compliance. She wasthe only child who had contact lenses instead ofglasses.The duration oftreatment until cure in relation

to the age at the start of treatment of compliantchildren is presented in Figure 2. The treatmenttime needed to achieve cure for the strabismicchildren was related to age, with shorter timeperiods needed on average for the younger

4)-I

0

Figure 2 Time to cure(days) vs age (years) for allcured compliant cases withstrabismus (n=23) andanisometropia (n= 12).Strabismus 0.Anisometropia 0.

100-

80-

0

E-2

60-

40-

20-

0

0

0

0

0o 0

00

0

H 00

00

0 00

0

0

0

0

0 8000

0 0 0* o

0,1 0,2 0,3 0,4 0,5

V'isual Acuity at start

0,6 0,7

Figure 3 Time to cure (days) vs visual acuity (VA) at start oftherapyfor all cured compliant children (n=35). *Indicatestwo identical data points. Strabismus E1. Anisometropia 0.

children. For the compliant anisometropes no120 0 obvious relation to age was found in the limitedage range studied for this group. A more directcomparison between the treatment time needed

100 for stabismic (n=8) or anisometropic (n=7)children aged 4 years, all treated only withrepeated patching, revealed that time to cure was

0 in a similar range for both groups in spite of a80 generally lower VA at the start for the strabismic

0 group. The treatment time until cure ranged0

from 10 to 80 days for all 4-year-old children60 0 0 compliant to patching. The treatment time to

0 cure for most strabismic and anisometropic cases

0z between 2 and 7 years old with good complianceto any form ofamblyopic therapy was 100 days or

40- °0 less (Fig 2). It was not related to initial degree of0 0 0 0 § amblyopia (Fig 3)

0 0 Although the treatment regimens other than° patching were successful in cases with good

20 compliance, the treatment time to cure, in00 general, was longer than that for the group with0 0 00 patching. One 7-year-old boy (case 4, outside the

0 time scale in Figs 2 and 3) with microstrabismus0 1 2 3 4 5 6 (initial VA of 0-2) and treatment with atropine

had a treatment time (over 200 days) strikinglyAge (years) longer than the others. However, six children

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out of 10 with atropine or Ryser filter treatmentwere cured within 50 days or less.To compare the rate of improvement with

respect to age and type or grade of amblyopia weevaluated the time needed to improve to thelogarithmic half point of VA improvementbetween start and cure (Figs 4A, B). The timeneeded to reach this half point was on averageshorter at 2 years than at 4 years of age for thestrabismic children (Fig 4A). No obviouscorrelation was found between VA at start oftreatment and the time to improve to this halfpoint (Fig 4B). The average improvement duringthe first weeks of treatment in relation to VA atthe start is demonstrated in Fig 5 for threerepresentative groups children, namely thosewith visual acuity at the start of 0-1, 0 3, and0 5.Of the total group of 44 children eight showed

no or low compliance during the whole or part ofthe treatment period (Tables 1 and 2). Four ofthe children in this group were cured in spite oflow compliance, but a long treatment period wasneeded (156 to 412 days). Among the compliantchildren achieving cure (n=35) only one had atreatment time in this time range. Five of thecases with low compliance were anisometropeswithout strabismus with moderate amblyopia(VA 01-0-3) at start of treatment (Table 1).Among all the anisometropic cases with moderateamblyopia at the start the non-compliantchildren accounted for almost 2/3 (Table 1). Themean age of the children with low compliancewas 5 1 years and that of children with goodcompliance 4-2 years at the start of treatment.However, an age of 2 years (case 18 and 38) wasno guarantee ofgood compliance.

700

0

60

-" 50

40

300

0

10 0 00.

0 0H o u. o

.0 . . .

0

Occlusion amblyopia was not registered in our36 compliant children during the treatmentperiod described here, though we observed thatthree cases on one occasion had one line ofpoorerperformance in the good eye. At the followingtest the visual acuity returned to normal, thoughocclusion of the good eye was continued.

DiscussionThis prospective study of children with pre-viously untreated amblyopia was initiated inorder to delineate limiting factors for cure and tofind the reason for failures in different agegroups from 2 years and above. A prerequisitefor the study of age as a predicting factor for theoutcome ofamblyopia treatment is tests of acuitysuitable for ages from 2 years. In all childrenbelow 3 years of age included in this study wecould get reliable and reproducible informationon visual acuity based on the same general testprinciple as those used for the older children'° 13(Lithander in preparation). The main differenceamong the optotype tests was the inability to testcrowding at the youngest age, since the 0 testtests acuity for single symbols at near (Lithander,in preparation).The main question in our study was whether

anything could be gained by lowering the age forscreening of amblyopia below 4 years. We foundno crucial age related differences in the finaloutcome of treatment, even though the youngerage groups showed shorter treatment times. Allbut one of the compliant children were cured,regardless of age (between 2 and 7 years),diagnosis, and severity of amblyopia. Thereforethe present screening program used in Swedenseems adequate. Children with low visual acuityin one or both eyes are detected and referred atthe screening age of 4. At any age squint or anyother eye disease observed by parents or at thehealth centre are referred directly to an ophthal-mologist for examination and treatment.

70-

60-

50*U,

-0 40*

30

F-

20-

10-

2 3 4 5 6 7 0 0,1 0,2

00

0

00

00 0

r.3 OE A 8M**0 0 8

O 0 0 0 0** 0

0,3 0,4 0,5 0,6 0,7Age (years)

Figure 4AVisual Acuity at start

Figure 4B

Figure 4 Initial rate ofimprovement. Time (days) to halfpoint (log VA start+log VA cure) between VA at start and2

cure for all cured compliant children. (A) Versus age (years) at start of treatment. (B) versus initial degree of amblyopia.*Indicates two identical data points.

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Anisometropic and strabismic amblyopia in the age group 2years and above: a prospective study ofthe results oftreatment

Table 2 Clinical characteristics ofpatients (n=8) with lowcompliance

Case no Age Visual acuityTime to cure

Start Cure (days)

Strabismus18 2 03 05 15638 2 <0 1 05 20640 9 01 0-2* 150*Anisometropia11 4 0-5 0-8 22839 4 0-3 0-6* >1000*42 7 0-2 0-6* 325*43 6 0-2 0-6* 130*44 4 0-2 0-8 412

*Cure not achieved; no co-operation obtained for furthertreatment.

Another major finding in our study was thatgood compliance to any form of amblyopic treat-ment was associated with more than 95% cure,whereas only 50% of the children with low com-pliance were cured. Neumann et all found that a

higher proportion of younger children (2-5 5years) were more compliant to patching thanchildren older than 8 years (72% versus 47%).They concluded that this was probably the pri-mary reason for the higher percentage. of treat-ment failures in older children. Our study showsthat low compliance to any form of therapy is alsothe primary factor for treatment failure in childrenat any age between 2 and 7 years. The childrenwith low compliance in our study were on

average about one year older at start of therapy.Compliance thus seems to be the main factor

for cure, except for those rare cases with therapy-resistant amblyopia, in which amblyopia isprobably induced within the first years of life.64Emphasis should therefore be placed on adher-ence to therapy during amblyopia treatment, andinitial and repeated information about theimportance ofcompliance to treatment should begiven to the family. Follow-up even after a weekor two weeks of treatment is rewarding for thevisual acuity has improved in most cases (Fig 5),and the child and the parents are hereby encour-

aged to go on with the treatment. One possiblereason for the low improvement rate of severe

amblyopia found in some studies8 could be lowcompliance.

0-9

0.8

0-7

0-6

0-5-2 054>u

Time (weeks)

Figure 5 Rate ofimprovement during thefirst weeks ofamblyopia treatment in relation to visual acuity oftheamblyopic eye at start. The range ofVA at one to eight weeksafter start is presentedfor three representative groups ofcuredcompliant children with initial VA of-0 1 (n=5), 0 3(n= 10), and 0O5 (n=5). The ranges overlapfor the twogroups, with higher initial VA betweenfour and eight weeks asindicated andfor the group with initial VA -0 1 at eightweeks. Identical range limits are indicated by doublehorizontal bars.

Although we put much time and effort intoinformation we had eight out of44 with low or nocompliance. Five of these children had moderateamblyopia - that is, visual acuity 0-I to 0 3 due toanisometropia without strabismus. In the aniso-metropic group with mild amblyopia - that is,visual acuity above 0-4 - we had no problemswith compliance. Neumann et all' also reportedthe lowest rate of compliance in the group withanisometropic amblyopia.The question arises why it is so difficult for the

anisometropic child with visual acuity of 0' 1-0 3to accept a patch. A probable answer is that lowerdegree of motivation for treatment was presentfor patients in this group with straight eyes. Ourfive anisometropic children with low compliancewere treated for long periods (years), and periodsof adequate compliance were obtained. All ofthem had improvement of at least three lines andtwo were finally cured, so their amblyopia isprobably not resistant to therapy. However, ourstudy cannot rule out the possibility that thetherapeutic responses in anisometropia andstrabismic amblyopia are different. It is interest-ing to note that the two types of amblyopia havedifferences in psychophysical characteristics.'6I8The treatment time needed to achieve cure,

namely one line difference or less between theeyes, was highly dependent on compliance butnot on the initial type or degree of amblyopia. Allbut two of the compliant children were curedwithin three months of treatment regardless ofinitial visual acuity or type of amblyopia incontrast to the children with lower compliance.Treatment regimen and type of amblyopiatherefore seems to have limited impact on thetime needed to achieve cure. Similarly, Oliver etal and Neumann et al'5 reported that most of theimprovement of visual acuity occurred duringthe first three months oftreatment independentlyof type or initial degree of amblyopia. The rate ofinitial improvement in our compliant childrenshowed no obvious correlation with visual acuityat the start of treatment, though a tendency maybe observed. Neumann et all' have reported aquicker recovery of visual acuity after threemonths of treatment in children (aged 2-7 years)with more severe amblyopia at the start.Our study hypothesis that age is a strong factor

in the outcome of amblyopia treatment was notsupported. Instead we found that the age of thechild was not critical for a successful result.However, the number of children above 5 yearsof age in our study was limited. Age was onlyweakly associated with the time needed to achievecure in the age group 2-7 years in cases with goodcompliance. Similarly, Oliver and Nawratzki4found that up to the age of 6 years goodtherapeutic results (about 65%) were obtained inall age groups. They stated that most childrenwith amblyopia can be effectively detected at theage of 4 years and concluded that this ageprobably is the best age for screening, also takinginto account that the prevalence of amblyopia islower below 3 years of age.4 At 2 years of age ourstrabismic children were cured somewhatquicker than the older ones, but this differencein cure rate is of limited practical importance ifwe consider the lower accuracy of acuity testingunder screening conditions at earlier ages. Fulton

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and Mayer'9 reported similar results in a retro-spective study of the relationship between ageand duration of full-time occlusion in squintingchildren and demonstrated that older childrenshow a slower rate of acuity improvement duringpatching. Sattler9' found a quick recovery withinthe first three months of treatment for 3-year-oldchildren with squint than for those aged 7 orabove.

Flynn and Cassady2' demonstrated a decreas-ing percentage of successful results and pro-longed duration oftherapy in amblyopic childrenwith start of therapy after 5 years of age.Screening after the age of 6 is therefore probablysuboptimal from the therapeutic point of view.

In summary, in our study, designed to beoptimal for amblyopia treatment, we found thatthe patient's compliance was the main factor inachieving cure in most cases with strabismus andanisometropia in children between 2 and 7 years.Most of the improvement occurred during thefirst months and the majority (>90%) were curedwithin three months irrespective of age between2 and 7 years. Visual acuity screening at 4 yearsof age seems to be advantageous and efficaciousin order to detect and thereafter initiate success-ful treatment of most cases ofamblyopia withoutobvious squint.

This work was funded by a grant from the Swedish MedicalResearch Council (no. 02226), First of May Flower AnnualCampaign for Children, and Handlanden Svenssons fond.We thank Maths Abrahamsson for help with the illustrations

and for useful discussions and Lena Kjellberg for skilful assistance.

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