1 evidence based treatment of amblyopia in 2005 what we have learnt from the pediatric eye disease...
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1
Evidence Based Treatment of Amblyopia
in 2005
What we have learnt from the Pediatric Eye Disease Investigator Group [PEDIG]
Lionel Kowal
2
• Amblyopia is the most common cause of monocular visual impairment in children.
• Existing data on the treatment of amblyopia largely retrospective / uncontrolled.
Rationale for PEDIG Amblyopia Studies
3
PEDIG : Network of community & university- based ophthalmologists and
optometrists• A Randomized Trial of Atropine Versus Patching for
Treatment of Moderate Amblyopia in Children - ATS 1• A Randomized Trial Comparing Part-time Versus Full-time
Patching for Severe Amblyopia - ATS 2A• A Randomized Trial Comparing Part-time Versus Minimal-
time Patching for Moderate Amblyopia - ATS 2B• Prospective Study of Recidivism After Cessation of
Amblyopia Treatment - ATS 2C• An Evaluation of Treatment of Amblyopia in
Children 7-<18 Years Old – ATS3• A Randomized Trial of Atropine Regimens for Treatment of
Moderate Amblyopia in Children – ATS4
ATS1 4
Amblyopia Treatment StudyATS 1
A Randomized Trial of Atropine Versus Patching
for Treatment of Moderate Amblyopia in Children
The Pediatric Eye Disease Investigator Group. A randomized trial of atropine vs patching for treatment of moderate pamblyopiaArchives of Ophthalmology 2002;120:268-278
ATS1 5
• To compare patching and atropine as treatments for moderate amblyopia in children 3 to <7 years old
• To develop estimates of the success rates of treatment
• To identify factors that may be associated with successful treatment
Objectives
ATS1 6
• A randomized, controlled single-masked multi-center clinical trial
• 2 treatment groups
• Primary outcome: VA @ 6 mo
• Treatment after 6 mo: investigator discretion
Patching
Atropine
Study Design
ATS1 7
Eligibility Able to measure VA with single surrounded
HOTV
• Strabismic and/or anisometropic amblyopia
• Visual Acuity: – Amblyopic eye: 6/12 to 6/30– Sound eye: 6/12 or better– 3 lines or more interocular difference
• < 2 mo of amblyopia therapy in prior 2 y
ATS1 8
Electronic Visual Acuity Tester
20/400 20/200 20/100 20/50 20/25
Holmes, JM, Beck, RW, et al The Amblyopia Treatment Study Visual Acuity Testing Protocol Archives of Ophthalmology 2001:119;1345-1353.
ATS1 9
Patching Treatment
• Initial– 6 h/d up to all waking hours at investigator’s
discretion
• Subsequent (@ 17 w)– If <6/9 and <3 line improvement, increase up to
all or all but one waking hours
– If >6/9 or >3 line improvement, investigator could decrease patching to a minimum of 1 h/d
ATS1 10
Atropine Treatment
• Initial– 1 drop atropine 1% daily in sound eye
• Subsequent (@ 17 w)
– If <6/9 and <3 line improvement, replace hypermetropic lens of sound eye with plano
– If >6/9 or >3 line improvement, investigator could decrease atropine to 2/w
ATS1 11
Amblyopia Treatment Index• Questionnaire of 18 items, each scored from 1 to 5,
with 5 representing the most difficult
• Three subscales measured
adverse effects of treatment difficulties with compliance social stigma of treatment
• Items are summed to create each subscale score, then scaled to a common range
The Pediatric Eye Disease Investigator GroupImpact of Patching and Atropine Treatment on the Child and Family in the Amblyopia Treatment Study Archives of Ophthalmology 2003:121;1625-1632
ATS1 12
Patient Characteristics
Female 47%
Caucasian 83%
African American 5%
Hispanic 6%
Asian 2%
Mixed 2%
Other 2%
N=419
ATS1 13
<3 y 2%
3 to <4 y 15%
4 to <5 y 20%
5 to <6 y 33%
6 to <7 y 30%
Mean Age 5.3 y
Age n=419
ATS1 14
Strabismus 38%
Anisometropia 37%
Combined-mechanism 24%
Cause of Amblyopia n=419
Prior Treatment
26% received previous treatment for amblyopia
ATS1 15
Patient Follow Up
Patching Group215
Atropine Group204
6 Month Exam Completed 208 (97%)
Patients Randomized419
6 Month Exam Completed194 (95%)
2 Year Exam Completed 176 (86%)
2 Year Exam Completed 187 (87%)
ATS1 16
Patching Group: Number of Hours of Patching Prescribed
43%
30%
20%
7%
6 hours
8 hours
10 hours
>=12 hours
At Enrollment
30%
27%
33%
10%
6-7 hours
8-9 hours
>=12 hours
Maximum
10-11 hours
The number of hours prescribed at baselinewas the maximum for 80% of patients
ATS1 17
Atropine Group
• All patients prescribed one drop of 1% atropine daily
• A plano spectacle lens was prescribed for the sound eye during follow up for 56 /194 patients
ATS1 18
Amblyopic Eye Acuity at 6 Months
Patching Atropine (N=208) (N=194)
Mean improvement from 3.16 lines 2.84 linesbaseline
Mean acuity at 6 months 6/9 6/9-2
(Snellen approximation)
>6/9 or >3 line improvement from baseline 79% 74%
ATS1 19
0%
20%
40%
60%
80%
100% Patching
0%
20%
40%
60%
80%
100%
Atropine
Amblyopic Eye at 6 MonthsA
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6-month Amblyopic Eye Visual Acuity
>20/16
>20/20
>20/25
>20/32
>20/40
>20/50
>20/63
>20/80
>20/100
>20/125
>20/160
N=208
N=194
ATS1 20
Amblyopic EyeMean Acuity at Each Visit
Patching Atropine20/20
20/25
20/30
20/40
20/50
20/60
20/80
20/60-
20/40
20/30- 20/30
20/50+
20/40+20/30-2
5 wks 6 mos0 wks 16 wks
ATS1 21
Treatment Effect in Subgroups at 6 Months
• Effect of treatment was similar in subgroups based on:
• Age: – <5 years old, >5 years old
• Cause of amblyopia: – strabismus, anisometropia, combined
• Baseline visual acuity in amblyopic eye– 20/80 to 20/100 , 20/40 to 20/60
ATS1 22
Effect of Treatment on Sound Eyeat 6 Months
• A decrease in visual acuity of 1 or more lines at 6 months:
patching - 17 patients (8%) atropine - 47 patients (23%)
• Some cases were due to improper refractive correction
• In other cases there likely was residual cycloplegia from atropine not having been discontinued
ATS1 23
Ocular Side EffectsAny ocular side effect 26%
Types of ocular side effectsLid/conjunctival irritation 4%Light sensitivity 18%Eye pain/headache 2%Other 2%
Facial Flushing 2%
Systemic Side Effects 3%
* Reported at any visit in first 6 months
Atropine Side Effects*N=208
ATS1 24
Skin Irritation
Mild 41%
Moderate/Severe 6%
* Reported at any visit in first 6 months
Patching Side Effects*N=215
ATS1 25
Amblyopia Treatment Index• Both treatments were well tolerated
• All 3 subscale scores were consistently worse in the patching group
Median ScoreSubscale Patching AtropineAdverse Effects 2.25 2.00
Difficulty with Compliance 2.20 1.80
Social Stigma 3.00 2.00
ATS1 26
Amblyopic Eye Acuity at 2 YearsPatching Atropine
(N=188) (N=179)
Mean improvement from 3.7 lines 3.6 linesbaseline
Mean acuity at 2 years 20/32+2 20/32+1
(Snellen approximation)
>20/32 or >3 line improvement from baseline 86% 84%
Two-year follow-up of a 6-month randomized trial of atropine vs patching for treatment of moderate amblyopia in children.Arch Ophthalmol. 2005 Feb;123(2):149-57.
ATS1 27
0%
20%
40%
60%
80%
100%
Atropine
0%
20%
40%
60%
80%
100% Patching
Amblyopic Eye at 2 YearsA
mb
lyop
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6-month Amblyopic Eye Visual Acuity
>20/16
>20/20
>20/25
>20/32
>20/40
>20/50
>20/63
>20/80
>20/100
>20/125
>20/160
N=188
N=176
ATS1 28
Summary
• There was substantial improvement in amblyopic eye visual acuity with both treatments
• Improvement was more rapid in the patching group
• The difference between groups in amblyopic eye acuity at six months was small (about a third of a line)
• There was no difference between groups in amblyopic eye acuity after 2 years
ATS2 29
Amblyopia Treatment StudyATS 2A, 2B, 2C
AN EVALUATION OF PATCHING REGIMENS
ATS2 30
• Patching is most commonly prescribed. However, controversy exists concerning how much treatment is necessary.
• Most data on the response according to the daily dosage of patching are retrospective and uncontrolled.
• There is no standard of care once initial treatment of amblyopia is completed.
Rationale
ATS2 31
Randomized Trials
Patching 2 hours versus 6 hours daily for moderate amblyopia (20/40 to 20/80)
Patching 6 hours versus full-time for severe amblyopia (20/100 to 20/400)
ATS2 32
Eligibility• Age < 7 years
• Able to measure visual acuity with single surrounded HOTV optotypes
• Strabismic and/or anisometropic amblyopia
• Visual acuity: – Amblyopic eye: 20/40 to 20/400– Sound eye: 20/40 or better– 3 lines or more interocular difference
• No more than 2 months of amblyopia therapy in prior 2 years
ATS2 33
Severe Amblyopia Trial20/100-20/400
Moderate Amblyopia Trial 20/40-20/80
Randomize Randomize
Full-time patchingall or all but 1 hr per day
Part-timepatching
6 hrs per day
Part-timepatching
6 hrs per day
Minimal-timepatching
2 hrs per day
Visit A: 5 ± 1 weekVisual acuity testing both eyesOcular alignment assessmentAmblyopia Treatment Index
Visit B: 17 ± 1 weekVisual acuity testing (masked) both eyes
Ocular alignment assessmentStereoacuity Testing
Study Design
ATS2 34
Treatment ProtocolSevere amblyopia: 6 hours of patching
Full time patching
Moderate amblyopia: 2 hours of patching 6 hours of patching
All treatment groups were prescribed at least 1 hour of nearactivities while patching.
Investigator - Patching decreased to no less than 7 hours per week
Investigator - Patching could be continued, reduced, or stopped
ATS2B 35
Results ATS 2B
2 vs. 6 hours of patching
for moderate amblyopia (20/40 – 20/80)
The Pediatric Eye Disease Investigator GroupA Randomized Trial of Patching Regimens for Treatment of Moderate Amblyopia in ChildrenArchives Of Ophthalmology 121:2003;603-611
ATS2B 36
Patient CharacteristicsN=189
Female 44%
Caucasian 85%
Age (mean) 5.2 years
Cause of Amblyopia
Strabismus 40%
Anisometropia 33%
Combined 27%
Prior Amblyopia Treatment 14%
ATS2B 37
Patient Follow Up
2 Hour Groupn=95
6 Hour Groupn=94
Patients Randomized
N=189
4-MONTHMASKED
EXAM
Completedn=92
(97%)
Completedn=89
(95%)
ATS2B 38
Amblyopic Eye Acuity at 4 Months2 Hours
Patching
N=92
6 Hours
Patching
N=89
Mean improvement from baseline 2.4 lines 2.4 lines
Mean acuity at 4 months
(Snellen approximation)20/32-2 20/32-2
>20/32 or >3 line improvement from baseline
62% 62%
ATS2B 39
Amblyopic EyeMean Acuity at Each Visit
20/32
20/40
20/50
20/63
20/80
20/63+20/63+
Mea
n V
isua
l Acu
ity
Scor
e
2 Hours N=95
6 Hours N=94
Baseline
20/40+20/40+
2 Hours N=87
6 Hours N=85
5 Weeks
20/32-220/32-2
2 Hours N=92
6 Hours N=89
4 Months
ATS2B 40
Amblyopia Treatment Index• Both treatments were well tolerated.
• The subscale scores were similar between the groups on the adverse event and treatment compliance subscales.
• On the social stigma subscale, which includes questions related to the patch making the child feel different, the 6-hour group was worse.
Median ScoreSubscale 2 Hours 6 HoursAdverse Effects 2.13 2.13
Difficulty with Compliance 2.33 2.33
Social Stigma 2.67 3.00
ATS2B 41
Summary2 vs. 6 hours for moderate amblyopia
• Amblyopia improved with both patching regimens, when combined with prescribing 1 hour of near activities
• There was no demonstrable advantage to the greater number of hours either in the rapidity or magnitude of improvement after 4 months of treatment
ATS2B 42
Summary - Adverse Effects
• We found no indication that 6 hours of patching compared with 2 hours of patching was associated with a higher rate of adverse effects on the sound eye acuity
• New heterotropias were rare
ATS2B 43
Conclusions
• When combined with prescribing 1 hour of near activities, 2 hours of daily patching appears to be as effective as 6 hours of daily patching in treating moderate amblyopia in children 3 to < 7 years of age
• A shorter duration of patching may ease the implementation of patching therapy and monitoring compliance for some parents
ATS2A 44
Results ATS 2A
6 hours vs. full time patching for severe amblyopia (20/100 – 20/400)
The Pediatric Eye Disease Investigator GroupA Randomized Trial of Prescribed Patching Regimens for Treatment of Severe Amblyopia in Children Ophthalmology 2003:11;2075-2087
ATS2A 45
Patient CharacteristicsN= 175
Female 46%
Caucasian 83%
Age (mean) 4.8 years
Cause of Amblyopia
Strabismus 27%
Anisometropia 34%
Combined 38%
Prior Amblyopia Treatment 14%
ATS2A 46
Patient Follow Up
6 Hour Groupn=85
Full-time Groupn=90
Patients Randomized
N=175
4-MONTHMASKED
EXAM
Completedn=73
(86%)
Completedn=84
(93%)
ATS2A 47
Amblyopic Eye Acuity at 4 Months
6 Hours
Patching
N=73
Full-time
Patching
N=84
Mean improvement from baseline 4.8 lines 4.7 lines
Mean acuity at 4 months
(Snellen approximation)20/50 20/50-2
ATS2A 48
Amblyopic EyeMean Acuity at Each Visit
20/160
20/200
20/125
20/063
20/080
20/100
20/250
20/050
20/040
Mea
n V
isu
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cuit
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core
Full-time N=90
Six-hrs N=85
Baseline Exam
20/16020/160+1
Full-time N=77
Six-hrs N=75
Five-week Exam
20/63-220/63-2
Full-time N=84
Six-hrs
N=73
Four-month Exam
20/5020/50-2
ATS2A 49
Treatment Effect in Subgroups at 4 Months
Effect of treatment was similar in subgroups based on:• Age:
– <5 years old, >5 years old
• Cause of amblyopia: – strabismus, anisometropia, combined
• Baseline visual acuity in amblyopic eye– 20/100 to 20/160 , 20/200 to 20/400
ATS2A 50
Amblyopia Treatment Index• Both treatments were well tolerated
• The subscale scores were similar between the groups on the adverse event, treatment compliance, and social stigma subscale subscales
Median ScoreSubscale 6 Hours Full-TimeAdverse Effects 2.25 2.50
Difficulty with Compliance 2.33 2.42
Social Stigma 3.00 3.00
ATS2A 51
Summary6 hrs vs. full-time for severe amblyopia
• Amblyopia improved with both prescribed patching regimens, when combined with prescribing 1 hour of near activities
• Compared to 6-hour patching, there was no demonstrable advantage to full-time patching in the rapidity or the magnitude of improvement after 4 months of treatment
52
Amblyopia Recurrence ATS 2C
• Prospective observational study
• 156 children with successfully treated amblyopia – ready to stop treatment
• Treatment STOPPED at enrollment
Risk of amblyopia recurrence after cessation of treatment.J AAPOS. 2004 Oct;8(5):420-8.
53
Previous Rx
Enrollment156 children
5w 13w 26w 52wStudy period – off treatment
Study Design
Treatment STOPPED
54
Recurrence overall during 1-year follow-up
Recurrence ( 2 logMAR -Confirmed by repeat testing)21% (95% CI 14% to 28%)
Alternative Definition – Non replicated 2 logMAR VA
No recurrenceAll recurrences - 24%(95% CI 17% to 32%)
21%
3%
55
Timing of the 35 recurrences
100
110
120
130
140
150
0 5 10 15 20 25 30 35 40 45 50
Pts
Weeks
14 (40%)
10 (29%)5 (14%)
6 (17%)
56
Patching vs Atropine
Patching Stopped (77% pts)
Atropine Stopped (23% pts)
25% Recurrence (95% CI 17% to 34%)
21% Recurrence (95% CI 7% to 35%)
57
Patching hours stopped
0%
20%
40%
60%
80%
100%
2h >2<6h 6-8h >8h
Patching hours stopped at enrollment
Recurrence 15% 18% 43% 43%
P=0.008
58
Conclusions of Amblyopia Recurrence Study
• ¼ of successfully amblyopic children experience a recurrence over 1 year of f/u
• Recurrence risk is similar for stopping patching and atropine
• Most recurrences occur within 3 months – early follow-up is critical – but long term follow-up is also important
• If 6 or more hours of patching stopped – recurrence risk is lower if patching is reduced to 2 hours per day before cessation – suggests “weaning” is beneficial
ATS3 59
An Evaluation of Treatment of Amblyopia in
Children 7-<18 Years Old – ATS3
Supported by the National Eye
Institute
ATS3PS 60
PEDIG Pilot Study
Eligibility • Age 10 to <18 years
• Amblyopic eye acuity of 20/40 to 20/160
Treatment • >2 hours daily patching
• At least one hour of near activities during patching
Outcome: Visual acuity after two months of treatment
Results: Visual acuity improved >2 lines in 18 (27%)
of 66 patients
A prospective, pilot study of treatment of amblyopia in children 10 to <18 years old.Am J Ophthalmol. 2004:137;581-583.
ATS3 61
•To determine the response rate to amblyopia treatment in children from 7 to <18 years
•To determine the frequency of recidivism of successfully-treated amblyopia in children 7 to <18 years
Objectives
ATS3 62
Eligibility
• Age 7 years to <18 years
• Amblyopia associated with strabismus, anisometropia, or both
• Best corrected visual acuity in the amblyopic eye 20/40 to 20/400
• Best corrected visual acuity in the sound eye 20/25 or better
• No myopia in amblyopic eye >-6.00 D spherical equivalent
• No amblyopia treatment (other than spectacles) in the past month and no more than one month of amblyopia treatment in the last 6 months
ATS3 63
•Randomized, controlled multi-center clinical trial
•Sample size: >360 children (>90 in each of 4 age groups)
•Treatment groups:
Control Group: Optical correction only
Active Group: Optical correction Patching plus near activities
Atropine (patients <13 yrs only)
•Primary analysis: Comparison of proportion of treatment
responders between treatment groups
Study Design
ATS3 64
Enrollment Prescription of spectacles
Randomization (within 30 days of enrollment)Visual acuity testing in new spectacles
Randomized Trial Follow Up
Post-randomized Trial Follow Up
Observation Phase Follow Up Treatment is discontinued
End of Study
NonrespondersResponders
Active Group Control Group
Study Flow
ATS3 65
Enrollment/Randomization
Screening/Enrollment Visit: • Patients are prescribed new spectacles (if needed)
Randomization Visit (within 1 month): • New spectacles are placed on patient for the first time
• Visual acuity is tested using E-ETDRS protocol, which yields a letter score
• Patient is randomized as long as visual acuity still meets eligibility criteria
ATS3 66
Treatment Groups
Patients are randomized to one of the following treatment
groups:
Control Group: • Optical correction only
Active Treatment Group: • Optical correction• Patching 2-6 hours daily• At least 1 hour of near activities daily during patching • Atropine 1% one drop daily (pts <13 yrs only)
ATS3 67
Randomized Trial Follow UpFollow-up visits occur every 6 weeks up to 24 weeks
• Visual acuity is tested with the E-ETDRS protocol
• Using the best of two measured amblyopic eye visual acuities, the patient is classified as a responder, nonresponder or neither
• When the patient meets criteria for either responder or non-responder and this is confirmed by masked exam, the randomized trial is over
ATS3 68
Responder/Nonresponder Criteria
Responder Criteria: 10 letter (2 line) or more improvement in amblyopic eye acuity compared with acuity at randomization
Nonresponder Criteria: minimal improvement that is visit specific, but less than 10 letters by 24 weeks
ATS3 69
Post-Randomized TrialNonresponders:
– End study follow up – Control group patients may start on active treatment outside study
Responders: – Continue assigned treatment until no further improvement– Once improvement has stopped:
• Control Group patients end study, but may start on active treatment outside study
• Active Treatment Group patients discontinue treatment and enter the Observation Phase
ATS3 70
Observation Phase Visits occur at 13 wks, 26 weeks, and 52 weeks after
treatment discontinuation
• Visual acuity is assessed at each visit
• Recurrence: acuity 10 or more letters worse than acuity at treatment discontinuation
71
RESULTS
• 507 patients
• 49 sites– 1 to 33 patients/per site
72
Patient Characteristics 7 < 13 YRSN=404 (%)
TREATMENT (N = 201) OPTICAL CORRECTION (N = 203)AGE 9.8 (1.6) 9.5 (1.7)FEMALE 89 (44) 87 (43)NO PRIOR TREATMENT 96 (48) 99 (49)CAUSE OF AMBLYOPIAStrabismus 52 (26) 52 (26)Anisometropia 75 (38) 81 (41)Combined 73 (37) 66 (33)ACUITY IN AMBLYOPIC EYE20/200 - 400 16 (8) 18 (9)20/100 – 160 44 (22) 48 (24)20/40 – 80 141 (70) 137 (67)
73
Patient Characteristics 13 < 18 YRSN=103 (%)
TREATMENT (N = 55) OPTICAL CORRECTION (N = 48)AGE 14.7 (1.4) 14.9 (1.2)FEMALE 31 (56) 25 (52)NO PRIOR TREATMENT 36 (65) 33 (69)CAUSE OF AMBLYOPIAStrabismus 11 (20) 14 (29)Anisometropia 20 (36) 17 (35)Combined 24 (44) 17 (35)ACUITY IN AMBLYOPIC EYE20/200 - 400 2 (4) 3 (6)20/100 – 160 20 (36) 16 (33)20/40 – 80 33 (60) 29 (60)
74
Responder Rate 7 < 13 YRS
TREATMENT (N = 201) OPTICAL CORRECTION (N = 203)TOTAL 106 (53) 50 (25)AMBLYOPIA LEVEL 20/40 – 80 (N 141/137) 70 (50) 30 (22)20/100-400 (N 60/66) 36 (60) 20 (30)
PRIOR AMBLYOPIA TREATMENTYes (N 105/104) 42 (40) 14 (13)No (N 96/99) 64 (67) 36 (36)
N (%)* All Statistically Different
75
Responder Rate 13 < 18 YRS
TREATMENT (N = 55) OPTICAL CORRECTION (N = 48)TOTAL 14 (25) 11 (23)AMBLYOPIA LEVEL 20/40 – 80 (N 33/29) 7 (21) 6 (21)20/100-400 (N 22/19) 7 (32) 5 (26)
PRIOR AMBLYOPIA TREATMENTYes (N 38/28) 6 (16) 7 (25)No (N 17/20) * 8 (47) * 4 (20) *
N (%)* Suggestive of Difference
76
Conclusions• Amblyopic vision improves with optical
correction alone in about ¼ of all 7 to 17 Year Olds and ½ of 7 to 12 years olds with additional treatment.
• Amblyopic vision improves in 7 to < 13 year old children but not 13 to < 18 year olds who have been treated previously.
• All amblyopic eyes have remaining visual deficit.• Persistence of effect after treatment cessation is
unknown.
77
Amblyopia Treatment Study 4
(ATS4) A Randomized Trial of
Atropine Regimens for Treatment of Moderate Amblyopia in Children
78
Study Objectives
• To compare daily versus weekend atropine (two-days) for moderate amblyopia (20/40 to 20/80) in children 3 to <7 years old
• To determine the maximum amount of improvement that could be achieved with these atropine schedules.
79
Study Design
• A randomized, controlled, single-masked multi-center clinical trial
• 2 treatment groups:
• Primary outcome: Visual acuity at 4 months
• Secondary outcome: Maximum visual acuity improvement
daily atropine
weekend atropine
80
Eligibility
• Age < 7 years
• Able to measure visual acuity with single surrounded HOTV optotypes
• Strabismic and/or anisometropic amblyopia
• No amblyopia treatment in the past month and no more than 1 month of amblyopia treatment in the past six months
81
EligibilityVisual Acuity
• Amblyopic eye - 20/40 to 20/80
• Sound eye - > 20/40
• Inter-eye acuity difference - > 3 lines
82
Atropine Treatment
• weekend or daily atropine 1% solution was prescribed
• For patients in the daily atropine group, if the amblyopic eye acuity improved to be the same as or better than the sound eye acuity, atropine could be decreased to no less than twice per week
83
Visit Schedule
• 5-week visit
• Masked outcome visit at 4 months– Amblyopic eye at 17 weeks, sound eye and
binocularity at 19 weeks
• Additional visits at investigator discretion
• Partial responders returned every 8 weeks
84
Patient CharacteristicsN=168
Female 39%
Caucasian 79%
Age (mean) 5.3 years
Cause of Amblyopia
Strabismus 33%
Anisometropia 41%
Combined 23%
Prior Amblyopia Treatment 18%
85
Patient Follow-Up
Weekend Groupn=85
Daily Groupn=83
Patients Randomized
N=168
4-MONTHMASKED
EXAM
Completedn=83
(98%)
Completedn=77
(93%)
86
Amblyopic Eye at 4 Months
Weekend atropine
N=83
Daily atropine
N=77
Mean improvement from baseline 2.3 lines 2.3 lines
Mean acuity at 4 months
(Snellen approximation)20/32-1 20/32-1
>20/32 or >3 line improvement from baseline
66% 66%
87
0%
20%
40%
60%
80%
100%
6-Hours Patching
0%
20%
40%
60%
80%
100% 2-Hours Patching
Amblyopic Eye at 4 MonthsA
mb
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4-month Amblyopic Eye Visual Acuity
>20/16
>20/20
>20/25
>20/32
>20/40
>20/50
>20/63
>20/80
>20/100
>20/125
>20/160
N=92
N=89
0%
20%
40%
60%
80%
100%
Weekend Atropine
0%
20%
40%
60%
80%
100%
Daily Atropine
N=77
N=83
88
5 Weeks
20/40+120/40
Amblyopic EyeMean Acuity at Each Visit
20/32
20/40
20/50
20/63Mea
n V
isua
l Acu
ity
Scor
e
DailyN=83
WeekendN=85
Baseline
Daily N=78
Weekend N=81
DailyN=77
WeekendN=83
20/63+220/63+2
4 Months
20/32-120/32-1
89
Acuity at Study Completion
• 20/25 or better OR equal to sound eye– Daily - 39 (47%) – Weekend - 45 (53%)
• Mean Amblyopic eye acuity– Daily – 0.23 logMAR (20/32-3)
• 2.3 lines of improvement
– Weekend – 0.21 log MAR (20/32-1) • 2.5 lines of improvement
90
Treatment Effect in Subgroups
• Effect of treatment was similar in subgroups based on:
• Age: – <5 years old, >5 years old
• Cause of amblyopia: – strabismus, anisometropia, combined
• Baseline visual acuity in amblyopic eye– <20/63, >20/50
91
Effect of Treatment on the Sound Eye
• A decrease in sound eye visual acuity of 2 or more lines at 4 months:
Weekend atropine - 2 patients (2.4%) Daily atropine - 2 patients (2.6%)
• Further Follow-up Testing:• One in each group same as or better than
baseline• One in each group 20/32 compared with 20/20
at baseline
92
Other adverse effects
• Light sensitivity (no treatment changes)– Daily group – 13 (16%)– Weekend group – 25 (29%)
• Facial flushing / fever– 2 patients in daily group – 1 stayed on
treatment and 1 switched to homatropine
93
Ocular alignment
• 2 in daily and none in weekend developed > 8 deviation
• 2 in daily, 3 in weekend had disappearance of a microstrabismus
• 10% developed new strabismus or a preexisting angle of strabismus that had increased by at least 10
• 8% had their strabismus resolved or reduced by at least 10
94
Amblyopia Treatment Index• Both treatments were well tolerated.
• The subscale scores were similar between the groups on the adverse event and social stigma subscales.
• On the compliance subscale the weekend group was slightly worse.
Median ScoreSubscale Weekend DailyAdverse Effects 2.00 2.00
Difficulty with Compliance 2.10 2.00
Social Stigma 2.00 2.00
95
Conclusions
• Weekend atropine appears to be as effective as daily atropine in treating moderate amblyopia in children 3 to < 7 years of age
• A reduced frequency is another alternative treatment for amblyopia.
• The magnitude of the visual acuity improvement was similar to that seen for 2-hour and 6-hour prescribed patching regimens for moderate amblyopia.