Transcript The Amblyopia Treatment Study

Evidence Based Treatment of Amblyopia
in 2005
What we have learnt from the Pediatric Eye Disease
Investigator Group [PEDIG]
Lionel Kowal
1
Rationale for PEDIG Amblyopia Studies
• Amblyopia is the most common cause of
monocular visual impairment in children.
• Existing data on the treatment of amblyopia largely
retrospective / uncontrolled.
2
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 Minimaltime 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
3
Amblyopia Treatment Study
ATS 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 pamblyopia
Archives of Ophthalmology 2002;120:268-278
ATS1
4
Objectives
• 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
ATS1
5
Study Design
• A randomized, controlled single-masked
multi-center clinical trial
• 2 treatment groups
Patching
Atropine
• Primary outcome: VA @ 6 mo
• Treatment after 6 mo: investigator discretion
ATS1
6
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
7
Electronic Visual Acuity Tester
20/400
ATS1
20/200
20/100
20/50
Holmes, JM, Beck, RW, et al
The Amblyopia Treatment Study Visual Acuity Testing Protocol
Archives of Ophthalmology 2001:119;1345-1353.
20/25
8
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
9
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
10
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 Group
Impact of Patching and Atropine Treatment on the Child and Family in the Amblyopia Treatment Study
Archives of Ophthalmology 2003:121;1625-1632
ATS1
11
Patient Characteristics
N=419
ATS1
Female
47%
Caucasian
83%
African American
5%
Hispanic
6%
Asian
2%
Mixed
2%
Other
2%
12
Age
ATS1
n=419
<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
13
Cause of Amblyopia n=419
Strabismus
38%
Anisometropia
37%
Combined-mechanism
24%
Prior Treatment
26% received previous treatment for amblyopia
ATS1
14
Patient Follow Up
Patients Randomized
419
Patching Group
215
Atropine Group
204
6 Month Exam Completed
208 (97%)
6 Month Exam Completed
194 (95%)
2 Year Exam Completed
187 (87%)
2 Year Exam Completed
176 (86%)
ATS1
15
Patching Group: Number of
Hours of Patching Prescribed
At Enrollment
Maximum
>=12 hours
>=12 hours
20%
10 hours
7%
6 hours
33%
6-7 hours
43%
10% 27%
30%
8 hours
30%
10-11 hours
8-9 hours
The number of hours prescribed at baseline
was the maximum for 80% of patients
ATS1
16
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
17
Amblyopic Eye Acuity at 6 Months
Mean improvement from
baseline
Mean acuity at 6 months
(Snellen approximation)
>6/9 or >3 line
improvement from baseline
ATS1
Patching
Atropine
(N=208)
(N=194)
3.16 lines
2.84 lines
6/9
79%
6/9-2
74%
18
Amblyopic Eye at 6 Months
Amblyopic Eye Visual Acuity
Cumulative Distribution
100%
Patching
N=208
80%
60%
Atropine
40%
N=194
20%
0%
>20/16
>20/20
>20/25
>20/32
>20/40 >20/50
>20/63
>20/80 >20/100 >20/125 >20/160
6-month Amblyopic Eye Visual Acuity
ATS1
19
Amblyopic Eye
Mean Acuity at Each Visit
Patching
Atropine
20/20
20/25
20/30-
20/30
20/40
20/40
20/40+
20/50
20/60
20/30
20/30-2
20/50+
20/60-
20/80
0 wks
ATS1
5 wks
16 wks
6 mos
20
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
21
Effect of Treatment on Sound Eye
at 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
22
Atropine Side Effects*
N=208
Ocular Side Effects
Any ocular side effect
26%
Types of ocular side effects
Lid/conjunctival irritation
Light sensitivity
Eye pain/headache
Other
4%
18%
2%
2%
Facial Flushing
2%
Systemic Side Effects
3%
* Reported at any visit in first 6 months
ATS1
23
Patching Side Effects*
N=215
Skin Irritation
Mild
41%
Moderate/Severe
6%
* Reported at any visit in first 6 months
ATS1
24
Amblyopia Treatment Index
• Both treatments were well tolerated
• All 3 subscale scores were consistently worse in the
patching group
Subscale
Median Score
Patching Atropine
Adverse Effects
2.25
2.00
Difficulty with Compliance
2.20
1.80
Social Stigma
3.00
2.00
ATS1
25
Amblyopic Eye Acuity at 2 Years
Patching
Atropine
(N=188)
(N=179)
Mean improvement from
baseline
3.7 lines
3.6 lines
Mean acuity at 2 years
(Snellen approximation)
20/32+2
20/32+1
86%
84%
>20/32 or >3 line
improvement from baseline
ATS1
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.
26
Amblyopic Eye at 2 Years
Amblyopic Eye Visual Acuity
Cumulative Distribution
100%
Patching
N=188
80%
60%
Atropine
40%
N=176
20%
0%
>20/16
ATS1
>20/20
>20/25
>20/32
>20/40 >20/50
>20/63
>20/80 >20/100 >20/125 >20/160
6-month Amblyopic Eye Visual Acuity
27
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
ATS1
28
Amblyopia Treatment Study
ATS 2A, 2B, 2C
AN EVALUATION OF PATCHING REGIMENS
ATS2
29
Rationale
• 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.
ATS2
30
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
31
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
32
Study Design
Severe Amblyopia Trial
20/100-20/400
Randomize
Full-time patching
all or all but
1 hr per day
Part-time
patching
6 hrs per day
Moderate Amblyopia Trial
20/40-20/80
Randomize
Part-time
patching
6 hrs per day
Minimal-time
patching
2 hrs per day
Visit A: 5 ± 1 week
Visual acuity testing both eyes
Ocular alignment assessment
Amblyopia Treatment Index
ATS2
Visit B: 17 ± 1 week
Visual acuity testing (masked) both eyes
Ocular alignment assessment
Stereoacuity Testing
33
Treatment Protocol
Severe 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 near
activities while patching.
Investigator - Patching decreased to no less than 7 hours per week
Investigator - Patching could be continued, reduced, or stopped
ATS2
34
Results ATS 2B
2 vs. 6 hours of patching
for moderate amblyopia (20/40 – 20/80)
The Pediatric Eye Disease Investigator Group
A Randomized Trial of Patching Regimens for Treatment of Moderate Amblyopia in Children
Archives Of Ophthalmology 121:2003;603-611
ATS2B
35
Patient Characteristics
N=189
Female
44%
Caucasian
85%
Age (mean)
5.2 years
Cause of Amblyopia
Strabismus
40%
Anisometropia
33%
Combined
27%
Prior Amblyopia Treatment
ATS2B
14%
36
Patient Follow Up
Patients
Randomized
N=189
2 Hour Group
n=95
Completed
n=92
(97%)
ATS2B
6 Hour Group
n=94
4-MONTH
MASKED
EXAM
Completed
n=89
(95%)
37
Amblyopic Eye Acuity at 4 Months
2 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 or >3 line improvement
from baseline
ATS2B
20/32
62%
-2
20/32
-2
62%
38
Amblyopic Eye
Mean Acuity at Each Visit
Baseline
5 Weeks
4 Months
Mean Visual Acuity Score
20/32
20/32-2 20/32-2
20/40+ 20/40+
20/40
20/50
20/63
20/63+
20/63+
20/80
2 Hours
N=95
ATS2B
6 Hours
N=94
2 Hours
N=87
6 Hours
N=85
2 Hours
N=92
6 Hours
N=89
39
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 6hour group was worse.
Subscale
Adverse Effects
Median Score
2 Hours
6 Hours
2.13
2.13
Difficulty with Compliance
2.33
2.33
Social Stigma
2.67
3.00
ATS2B
40
Summary
2 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
41
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
42
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
ATS2B
43
Results ATS 2A
6 hours vs. full time patching
for severe amblyopia (20/100 – 20/400)
The Pediatric Eye Disease Investigator Group
A Randomized Trial of Prescribed Patching Regimens for Treatment of Severe Amblyopia in Children
Ophthalmology 2003:11;2075-2087
ATS2A
44
Patient Characteristics
N= 175
Female
46%
Caucasian
83%
Age (mean)
4.8 years
Cause of Amblyopia
Strabismus
27%
Anisometropia
34%
Combined
38%
Prior Amblyopia Treatment
ATS2A
14%
45
Patient Follow Up
Patients
Randomized
N=175
6 Hour Group
n=85
Completed
n=73
(86%)
ATS2A
Full-time Group
n=90
4-MONTH
MASKED
EXAM
Completed
n=84
(93%)
46
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)
ATS2A
20/50
20/50
-2
47
Amblyopic Eye
Mean Acuity at Each Visit
Baseline Exam
Five-week Exam
Four-month Exam
20/040
Mean Visual Acuity Score
20/050
20/50
20/063
20/63-2
20/50-2
20/63-2
20/080
20/100
20/125
20/160+1
20/160
20/160
20/200
20/250
ATS2A
Sixhrs
N=85
Fulltime
N=90
Sixhrs
N=75
Fulltime
N=77
Sixhrs
N=73
Fulltime
N=84
48
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
49
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
Subscale
Adverse Effects
Median Score
6 Hours
Full-Time
2.25
2.50
Difficulty with Compliance
2.33
2.42
Social Stigma
3.00
3.00
ATS2A
50
Summary
6 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
ATS2A
51
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.
52
Study Design
Enrollment
156 children
5w
Study period – off treatment
13w
26w
52w
Previous Rx
Treatment
STOPPED
53
Recurrence overall during 1-year follow-up
Recurrence ( 2 logMAR Confirmed by repeat testing)
21% (95% CI 14% to 28%)
21%
3%
Alternative
Definition –
Non replicated
2 logMAR VA
No recurrence
All recurrences - 24%
(95% CI 17% to 32%)
54
Timing of the 35 recurrences
150
140
Pts
14 (40%)
130
10 (29%)
120
5 (14%)
110
6 (17%)
100
0
5
10
15
20
25
30
Weeks
35
40
45
50
55
Patching vs Atropine
Patching Stopped (77% pts)
Atropine Stopped (23% pts)
21%
25%
75%
25% Recurrence
(95% CI 17% to 34%)
79%
21% Recurrence
(95% CI 7% to 35%)
56
Patching hours stopped
Recurrence 15%
18%
43%
43%
>2<6h
6-8h
>8h
100%
80%
60%
40%
20%
0%
2h
P=0.008
Patching hours stopped at enrollment57
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
58
An Evaluation of
Treatment of
Amblyopia in
Children 7-<18 Years
Old – ATS3
Supported by the National Eye
Institute
ATS3
59
PEDIG Pilot Study
A prospective, pilot study of treatment of
amblyopia in children 10 to <18 years old.
Am J Ophthalmol. 2004:137;581-583.
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
ATS3PS
60
Objectives
• 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
ATS3
61
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
62
Study Design
• 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
ATS3
63
Study Flow
Enrollment
Prescription of spectacles
Randomization (within 30 days of enrollment)
Visual acuity testing in new spectacles
Randomized Trial Follow Up
Responders
Nonresponders
Post-randomized Trial Follow Up
Active Group
Control Group
End of
Study
Observation Phase Follow Up
Treatment is discontinued
ATS3
64
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
65
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
66
Randomized Trial Follow Up
Follow-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
67
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
68
Post-Randomized Trial
Nonresponders:
– 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
69
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
ATS3
70
RESULTS
• 507 patients
• 49 sites
– 1 to 33 patients/per site
71
Patient Characteristics 7 < 13 YRS
N=404 (%)
AGE
FEMALE
NO PRIOR TREATMENT
CAUSE OF AMBLYOPIA
Strabismus
Anisometropia
Combined
ACUITY IN AMBLYOPIC EYE
20/200 - 400
20/100 – 160
20/40 – 80
TREATMENT (N = 201)
9.8 (1.6)
89 (44)
96 (48)
OPTICAL CORRECTION (N = 203)
9.5 (1.7)
87 (43)
99 (49)
52 (26)
75 (38)
73 (37)
52 (26)
81 (41)
66 (33)
16 (8)
44 (22)
141 (70)
18 (9)
48 (24)
137 (67)
72
Patient Characteristics 13 < 18 YRS
N=103 (%)
AGE
FEMALE
NO PRIOR TREATMENT
CAUSE OF AMBLYOPIA
Strabismus
Anisometropia
Combined
ACUITY IN AMBLYOPIC EYE
20/200 - 400
20/100 – 160
20/40 – 80
TREATMENT (N = 55)
14.7 (1.4)
31 (56)
36 (65)
OPTICAL CORRECTION (N = 48)
14.9 (1.2)
25 (52)
33 (69)
11 (20)
20 (36)
24 (44)
14 (29)
17 (35)
17 (35)
2 (4)
20 (36)
33 (60)
3 (6)
16 (33)
29 (60)
73
Responder Rate 7 < 13 YRS
TOTAL
AMBLYOPIA LEVEL
20/40 – 80 (N 141/137)
20/100-400 (N 60/66)
TREATMENT (N = 201)
106 (53)
OPTICAL CORRECTION (N = 203)
50 (25)
70 (50)
36 (60)
30 (22)
20 (30)
42 (40)
64 (67)
14 (13)
36 (36)
PRIOR AMBLYOPIA TREATMENT
Yes (N 105/104)
No (N 96/99)
* All Statistically Different
N (%)
74
Responder Rate 13 < 18 YRS
TOTAL
AMBLYOPIA LEVEL
20/40 – 80 (N 33/29)
20/100-400 (N 22/19)
TREATMENT (N = 55)
14 (25)
OPTICAL CORRECTION (N = 48)
11 (23)
7 (21)
7 (32)
6 (21)
5 (26)
6 (16)
8 (47) *
7 (25)
4 (20) *
PRIOR AMBLYOPIA TREATMENT
Yes (N 38/28)
No (N 17/20) *
* Suggestive of Difference
N (%)
75
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.
76
Amblyopia Treatment Study 4
(ATS4)
A Randomized Trial of
Atropine Regimens for Treatment of
Moderate Amblyopia in Children
77
Study Objectives
• To compare daily versus weekend atropine (twodays) 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.
78
Study Design
• A randomized, controlled, single-masked multicenter clinical trial
weekend atropine
• 2 treatment groups:
daily atropine
• Primary outcome: Visual acuity at 4 months
• Secondary outcome: Maximum visual acuity
improvement
79
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
80
Eligibility
Visual Acuity
• Amblyopic eye - 20/40 to 20/80
• Sound eye - > 20/40
• Inter-eye acuity difference - > 3 lines
81
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
82
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
83
Patient Characteristics
N=168
Female
39%
Caucasian
79%
Age (mean)
5.3 years
Cause of Amblyopia
Strabismus
33%
Anisometropia
41%
Combined
23%
Prior Amblyopia Treatment
18%
84
Patient Follow-Up
Patients
Randomized
N=168
Weekend Group
n=85
Completed
n=83
(98%)
Daily Group
n=83
4-MONTH
MASKED
EXAM
Completed
n=77
(93%)
85
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 or >3 line improvement
from baseline
20/32
66%
-1
20/32
-1
66%
86
Amblyopic Eye at 4 Months
Amblyopic Eye Visual Acuity
Cumulative Distribution
100%
2-Hours Patching
N=92
Weekend Atropine
80%
N=83
Daily Atropine
60%
N=77
6-Hours Patching
40%
N=89
20%
0%
>20/16
>20/20
>20/25
>20/32
>20/40 >20/50
>20/63
>20/80 >20/100 >20/125 >20/160
4-month Amblyopic Eye Visual Acuity
87
Amblyopic Eye
Mean Acuity at Each Visit
Baseline
5 Weeks
Mean Visual Acuity Score
20/32
4 Months
20/32-1
20/40
20/40
20/32-1
20/40+1
20/50
20/63+2
20/63+2
20/63
Daily
N=83
Weekend
N=85
Daily
N=78
Weekend
N=81
Daily
N=77
Weekend
N=83
88
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
89
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
90
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
91
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
92
Ocular alignment
• 2 in daily and none in weekend developed > 8D
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
10D
• 8% had their strabismus resolved or reduced by at
least 10D
93
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.
Subscale
Median Score
Weekend Daily
Adverse Effects
2.00
2.00
Difficulty with Compliance
2.10
2.00
Social Stigma
2.00
2.00
94
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 2hour and 6-hour prescribed patching regimens
for moderate amblyopia.
95