3. Amblyopia Treatment
Study-1 (ATS-01)
Atropine vs part-time patch,
moderate amblyopia
I. Arch Ophthalmol 2002: 120(3) 268-278
II. Arch Ophthalmol 2002: 120 (3) 281-287
III. Arch Ophthalmol 2003: 121 (11): 1625-32
IV. Arch Ophthalmol 2005: 123 (2): 149-157
V. J AAPOS 2005: 9 (6): 542-545
VI. Arch Ophthalmol 2008: 1039-1044
VII. JAMA Ophthalmol. 2014 July ; 132(7): 799–
805
AP Santiago MD 2016
4. Amblyopia Treatment
Study-1 (ATS-1)
Atropine vs part-time patch, moderate
amblyopia
I. Arch Ophthalmol 2002: 120(3)
268-278
VA 20/40-20/100
3 or more lines:
Atropine (74%) & Patching
(79%)
Atropine & patching similar for
age 3-7 yr
Atropine better acceptability
AP Santiago MD 2016
5. Amblyopia Treatment
Study-1 (ATS-1)
Atropine vs part-time patch,
moderate amblyopia
II. Arch Ophthalmol 2002:
120 (3) 281-287
Clinical profile of moderate
amblyopia subjects
moderate amblyopia
20/40-20/100
7 yrs and below
Same effect for strabismic
and anisometropic amblyopia
AP Santiago MD 2016
6. Amblyopia Treatment
Study-1 (ATS-1)
Atropine vs part-time patch, moderate
amblyopia
III. Arch Ophthalmol 2003: 121
(11): 1625-32
Impact of patching vs atropine
Both well tolerated by child and
family
Atropine more favorable
AP Santiago MD 2016
7. Amblyopia Treatment
Study-1 (ATS-1)
Atropine vs part-time patch,
moderate amblyopia
IV. Arch Ophthalmol 2005: 123
(2): 149-157
2 yr follow up after 6 month of
patching or atropine
Similar results in both groups
Amblyopic eye still 2 lines worse
than sound eye
AP Santiago MD 2015
8. Amblyopia Treatment
Study-1 (ATS-1)
Atropine vs part-time patch,
moderate amblyopia
V. J AAPOS 2005: 9 (6): 542-545
Effect of amblyopia tx on ocular alignment
Same rates of deterioration or improvement
in both groups
New strabismus by 2 yrs: most resolved after
cessation of treatment
18% in patching: 2 greater than 8PD
16% in atropine: 3 greater than 8PD
AP Santiago MD 2015
9. Amblyopia Treatment
Study-1 (ATS-1)
Atropine vs part-time patch,
moderate amblyopia
VI. Arch Ophthalmol 2008:
1039-1044
10 year follow up
improvement of amblyopia
maintained
Outcome similar for both
groups
residual amblyopia common
treatment initiated at age
3-7 years
AP Santiago MD 2015
http://www.ibeta.com
10. Amblyopia Treatment
Study-1 (ATS-1)
Atropine vs part-time patch,
moderate amblyopia
VII. JAMA Ophthalmol.
2014 July ; 132(7): 799–805
15 year follow up
improvement of amblyopia
maintained
Outcome similar for both
groups
Mild residual amblyopia
common
treatment initiated at age
3-7 years
AP Santiago MD 2015
http://logopond.com/
11. Amblyopia Treatment Study-2 (ATS-2)
(6h vs full; 2h vs 6h)
I. Ophthalmology 2003: 110(11) 2075-2087
II. Arch Ophthalmol 2003: 121 (5) 603-611
III. J AAPOS 2004: 8(5): 420-428
AP Santiago MD 2015
https://www.hosteurope.de
https://upload.wikimedia.org
https://blog.logos.com
12. Amblyopia Treatment Study-2A (ATS-2A)
Patch 6 hrs vs full time, severe amblyopia
I. Ophthalmology 2003: 110(11) 2075-2087
Full time: all waking hrs minus 1 hour off
Severe amblyopia: 20/100-20/400
Age 3-7 years
After 4 months
4.8 lines in 6 hrs group; vs 4.7 in full time
AP Santiago MD 2015
http://oceansignal.com
http://oceansignal.com
13. Amblyopia Treatment Study-2B (ATS-2B)
Patch 2 hrs (minimal time) vs 6 hrs (part time)
for Moderate amblyopia
II. Arch Ophthalmol 2003: 121 (5) 603-611
moderate: 20/40-20/80
ages 3-7 years
At 4 months: 2.4 lines in both groups with 1 hr of near
visual activity
AP Santiago MD 2015
https://www.hosteurope.de
https://upload.wikimedia.org
http://oceansignal.com
14. Amblyopia Treatment
Study-2C (ATS-2C)
Recurrence after cessation of
patching / Atropine
III. J AAPOS 2004: 8(5): 420-428
younger than age 8
3 months of amblyopia treatment
Recurrence same
24% of patched patients; 21% of
atropinized
1/4 experience recurrence within
1st year of cessation
RCT for weaning vs. no-weaning
AP Santiago MD 2015
15. Amblyopia Treatment Study-3 (ATS-3)
7 to < 18: spectacles vs atropine/patch
Arch Ophthalmol 2005: 123:
437-477 (Control)
Am J Ophthalmol 2004: 137:
581-583 (10-18yrs)
Arch Ophthalmol 2007: 125:
655-659
AP Santiago MD 2015
http://cdn4.teen.com
http://cdn4.teen.com
16. Amblyopia Treatment Study-3 (ATS-3)
7 to < 18: spectacles vs atropine/patch
ages 7-17 years
20/40-20/400
Given optimal optical correction
then randomized
Tx: glasses, patch plus near
activity, atropine
No Tx: glasses alone
AP Santiago MD 2015
http://cdn4.teen.com
17. Amblyopia Treatment Study-3 (ATS-3)
7 to < 18: spectacles vs atropine/patch
Responders: improved by >/= 10 letters / 2
lines
Amblyopia improves with Rx alone in 25%
Most patients left with residual VA deficit
Ages 7-12: tx improved amblyopia even if
previously treated
Ages 13-17: tx improved if no previous tx for
amblyopia
Unknown: if treatment results robust (if it will
stay)
AP Santiago MD 2015
http://cdn4.teen.com
18. Amblyopia Treatment Study-4 (ATS-4)
Atropine weekend vs daily; moderate amblyopia
Ophthalmology 2004: 111:
2076-2085
20/40-20/80
ages 3-7 years
Similar results with weekend
atropine vs daily atropine
2.3 lines in both groups
AP Santiago MD 2015
https://thejobshop.files.wordpress.com
19. Amblyopia Treatment Study-5 (ATS-5)
3 to < 7, spectacles alone vs patch 2 hrs + spectacles
Ophthalmology 2006: 113 (6) 895-903.
amblyopia improved with Rx by >/= 2
lines in 77%
amblyopia resolved in 27% with Rx
alone
3 line improvement average
Lessen the burden of amblyopia therapy
AP Santiago MD 2015
http://cdn4.teen.com
20. Amblyopia Treatment
Study-5 (ATS-5)
3 to <7, spectacles alone,
then patch 2 hrs vs spectacles
Ophthalmology 2006: 113 (6) 904-912.
• Strabismic and anisometropic amblyopia
• 20/40-20/400
• 2 hrs (1 hr near activity) + specs vs. specs alone
AP Santiago MD 2015
21. Amblyopia Treatment Study-5 (ATS-5)
spectacles alone, then patch 2 hrs vs spectacles
Ophthalmology 2006: 113 (6)
904-912.
5 wks: 1.1 lines treated; 0.5
lines specs
Any visit average: 2.2 lines
treated; 1.1 lines specs
After glasses, 2 hrs patching
(with 1 hr near activity)
improves moderate to severe
amblyopia
AP Santiago MD 2015
https://t2.ftcdn.net
✚http://cdn4.teen.com
22. Amblyopia Treatment Study-6 (ATS-6)
3 to <7, patch 2 hrs with near vs far activities after spectacles
J AAPOS 2005: 9: 129-136
Pilot: 4 wks: suggestion of greater
improvement in amblyopic eye with
near activities prescribed
2.6 lines near; 1.6 lines far (p=0.07)
AP Santiago MD 2015
http://www.adventuresetup.com
http://glacialblog.com
23. Amblyopia Treatment
Study-6 (ATS-6)
3 to <7, patch 2 hrs with near vs far
activities after spectacles
(VA 20/40 to 20/400)
AP Santiago MD 2015
Ophthalmology 2008; 115: 2071-78
At 8 wks: improvement in
amblyopic eye
Distance activity: 2.6 lines
Near activity: 2.5 lines 2.6 lines
near; 1.6 lines far (p=0.07)
Similar for both groups, even at 2, 5,
17 wks.
http://s7.photobucket.com
24. Amblyopia Treatment Study-6 (ATS-6)
3 to <7, patch 2 hrs with near vs far activities after spectacles
(VA 20/40 to 20/400)
AP Santiago MD 2015
Ophthalmology 2008; 115: 2071-78
3.6 lines improvement in severe amblyopic group
Near activities do not improve VA outcome in
anisometropic, strabismic, combined amblyopia with 2
hrs of daily patching
Severe amblyopia can respond even to 2 hrs of daily
patching
http://www.getbettergradesnow.com
25. Amblyopia Treatment Study-7 (ATS-7)
Bilateral refractive amblyopia; specs x 1 yr
(Response to treatment of previously untreated presumed bilateral
refractive amblyopia)
Am J Ophthalmol 2007: 144: 487-496
20/40-20/400
less than 10 years
Hypermetropia >/= 4.0D;
astigmatism >/= 2.0D
Eyeglasses alone improves binocular
VA to 20/25 or better within 1 year
AP Santiago MD 2015
http://cdn4.teen.com
26. Amblyopia Treatment Study-8 (ATS-8)
3 to <7, atropine vs Atropine plus plano lens to sound eye
Arch Ophthalmol 2009;127(1):
22-30
Moderate amblyopia .
20/40-20/100
Weekend atropine plus plano
lens = atropine alone
AP Santiago MD 2015
http://dissurat.net
27. Amblyopia Treatment Study-9 (ATS-9)
(7 to <13, ATS-1: weekend atropine vs. patch 2hours
Arch Ophthalmol. 2008;126(12):
1634-1642
Age 7-12; moderate amblyopia
20/40-20/100
Treatment with atropine or patching led to
similar degrees of improvement among 7-
to 12-year-olds with moderate amblyopia.
About 1 in 5 achieved visual acuity of
20/25 or better in the amblyopic eye.
Atropine and patching achieve similar
results among older children with
unilateral amblyopia
AP Santiago MD 2015
http://dissurat.net
https://t2.ftcdn.net
28. Amblyopia Treatment Study-10 (ATS-10)
Bangerter filters vs. patching
Ophthalmology 2010;117:998-1004. |
moderate amblyopia 20/40-20/80; 3-<10y.
At 24 wks, 1.9 lines improvement with Bangerter, vs.2.3 lines
in patching group
Because the average difference in visual acuity improvement
between Bangerter filters and patching was less than half a
line, and there was lower burden of treatment on the child
and family, Bangerter filter treatment is a reasonable option
to consider for initial treatment of moderate amblyopia.
AP Santiago MD 2015
29. ATS 11: A randomized trial to evaluate combined
patching-atropine treatment for residual amblyopia
Evaluate effectiveness of treatment of residual
amblyopia in 3-10y
VA 20/32 to 20/63 (mild residual amblyopia)
RCT: intensive treatment vs. rapid weaning plus glasses
Intensive: (42 hrs weekly dose plus daily atropine)
Pediatric Eye Disease Investigator Group. Randomized trial to evaluate combined patching and atropine for residual amblyopia.
Arch Ophthalmol 2011;129(7):960-2.
AP Santiago MD 2015
30. http://www.clipartbest.com
ATS 11: A randomized trial to evaluate combined
patching-atropine treatment for residual amblyopia
Intensive final push of combined treatment with patching
and daily atropine did not produce a better visual acuity
outcome after 10 weeks
Compared with a control group in whom treatment was
gradually discontinued
AP Santiago MD 2015
31. http://www.clipartbest.com
ATS 11: A randomized trial to evaluate combined
patching-atropine treatment for residual amblyopia
The study was stopped on recommendation of
the data and safety monitoring committee
slow recruitment
conditional power analysis indicating that the
study was unlikely to find a statistically
significant benefit
AP Santiago MD 2015
32. ATS 12: A randomized trial comparing patching with
active vision therapy to patching with control vision
therapy as treatment for amblyopia in children
7 to < 13 years old
Lyon DW, Hopkins K, Chu RH et al. Feasibility of a
clinical trial of vision therapy for treatment of
amblyopia. Optom Vis Sci 2013; 90(5): 475-481.
16 week vision therapy feasible
Standardizing approach to vision therapy not successful
AP Santiago MD 2015http://alderwoodvisiontherapy.com
33. ATS 13: An Observational Study of Optical
Correction for Strabismic Amblyopia in
Children 3 to < 7 years old
Optical Treatment of Strabismic and Combined Strabismic
Anisometropic Amblyopia. Ophthalmology 2012; 119:
150-158. Epub 2011 Sep 29.
VA after 18 weeks improved mean of 2.6 lines
75% >/= 2 line, 54% >/= 3 lines
Resolution of amblyopia in 32%
Greater in Strabismic Amblyopia alone (3.2 vs 2.3 lines)
VA improved regardless of whether alignment better
Optical treatment alone results in clinically meaningful
improvement; may consider as primary sole initial treatment
for this group
AP Santiago MD 2015
34. ATS 14: A Pilot Study to evaluate levodopa as
treatment for residual amblyopia in 8-17 years old
Repka MX, Kraker RT, Beck RW, et. al., Pediatric Eye
Disease Investigator Group. Pilot study of levodopa
dose as treatment for residual amblyopia in children
aged 8 years to younger than 18 years. Arch
Ophthalmol 2010;128(9):1215-7.
AP Santiago MD 2015
https://encrypted-tbn1.gstatic.com
35. ATS 14: A Pilot Study to evaluate levodopa as
treatment for residual amblyopia in 8-17 years old
At the time of enrollment, subjects
were required to have been treated
with at least 2 hours per day of daily
patching
And stable visual acuity
defined as less than 5 letters or one
logMAR line of improvement since a
previous visit at least 8 weeks earlier.
AP Santiago MD 2015
https://www.hosteurope.de
36. ATS 14: A Pilot Study to evaluate levodopa as
treatment for residual amblyopia in 8-17 years old
Intervention:
continuing 2 hours of daily patching
addition of levodopa in one of two doses
randomly assigned with equal probability
(0.51 or 0.76 mg/kg/tid, referred to as
lower dose and higher dose, respectively).
AP Santiago MD 2015
https://www.hosteurope.de✚
LEVODOPA
+
CARBIDOPA
37. ATS 14: A Pilot Study to evaluate levodopa as
treatment for residual amblyopia in 8-17 years old
Intervention:
The study medication was administered for 8 weeks with
one additional week for tapering of treatment.
Levodopa was prepared in capsules combined with
carbidopa 0.17 mg/kg/tid.
Carbidopa was combined with levodopa to reduce side-
effects associated with levodopa alone.
AP Santiago MD 2015
38. ATS 14: A Pilot Study to evaluate levodopa as
treatment for residual amblyopia in 8-17 years old
The mean improvement in amblyopic eye in 9-
week primary outcome visit was
+4 (±4) letters in the 16 subjects in the lower dose
group and
+6 (±6) letters in the 17 subjects in the higher dose
group
AP Santiago MD 2015
39. ATS 14: A Pilot Study to evaluate levodopa as
treatment for residual amblyopia in 8-17 years old
An improvement of 10 or more letters noted in 2 (13%)
in low dose, and 5 (29%) in high dose group at 9 wks
Fellow eye improved 1 letter in high dose and zero letter
is low dose group
Justification: Small sample, experience with drug,
promising result
AP Santiago MD 2015
40. ATS 15: Increasing patching for amblyopia study
from 2 hours to 6 hours
(3 to <8, 20/50 to 20/400)
When amblyopic eye VA stops improving with 2 hours of
daily patching, increasing the daily patching dosage to 6
hours results in more improvement in VA after 10 weeks
compared with continuing 2 hours daily.
Pediatric Eye Disease Investigator Group. A randomized trial of increasing patching
for amblyopia. Ophthalmology 2013 Nov;120(11):2270-7. Epub 2013 Jun 4
AP Santiago MD 2015
41. David K. Wallace, MD, MPH1; Elizabeth
L. Lazar, MSPH2; Earl R. Crouch III, MD3; Darren
L. Hoover, MD4; Raymond T. Kraker, MSPH2; Susanna
M. Tamkins, OD;
for the Pediatric Eye Disease Investigator Group. Time
course and predictors of amblyopia improvement with 2
hours of daily patching. JAMA Ophthalmol. 2015;133(5):
606-609. doi:10.1001/jamaophthalmol.2015.6.
AP Santiago MD 2015
ATS 15: Increasing patching for amblyopia study
from 2 hours to 6 hours
(3 to <8, 20/50 to 20/400)
42. ATS 16: Augmenting atropine treatment for
amblyopia with plano lens to sound eye
3 to <8, 20/50 to 20/400
Objective:
evaluate the effectiveness of adding a plano lens to weekend
atropine in patients with amblyopia still present after visual
acuity has stabilized with initial treatment.
Children ages 3 to <8 years with visual acuity of 20/50 to
20/400 in the amblyopic eye will be enrolled in a run-in
phase with weekend atropine until no improvement,
followed by randomization of eligible patients to weekend
atropine treatment with a plano lens over the sound eye
versus without a plano lens over the sound eye.
AP Santiago MD 2015
43. Objective:
evaluate the effectiveness of adding a plano lens to weekend
atropine in patients with amblyopia still present after visual
acuity has stabilized with initial treatment.
Children ages 3 to <8 years with visual acuity of 20/50 to
20/400 in the amblyopic eye will be enrolled in a run-in phase
with weekend atropine until no improvement,
followed by randomization of eligible patients to weekend
atropine treatment with a plano lens over the sound eye versus
without a plano lens over the sound eye.
AP Santiago MD 2015
J AAPOS 2015;19:42-48
ATS 16: Augmenting atropine treatment for
amblyopia with plano lens to sound eye
3 to <8, 20/50 to 20/400
44. Results:
atropine + plano lens = atropine only
1.1 vs 0.6, not statistically significant
Conclusion:
Small benefit to adding plano lens
Larger study recommended
AP Santiago MD 2015
J AAPOS 2015;19:42-48
ATS 16: Augmenting atropine treatment for
amblyopia with plano lens to sound eye
3 to <8, 20/50 to 20/400
45. Amblyopia Treatment Study-17 (ATS-17)
Levodopa for Residual Amblyopia
Ophthalmology. 2015 May;122(5):874-819
Objective: efficacy and short term safety of levopopa as
adjunctive treatment to amblyopia
139 children 7-12 years old
Strabismic &/or anisometropic amblyopia
Residual 20/50-20/400 with patching
AP Santiago MD 2015
46. Amblyopia Treatment Study-17 (ATS-17)
Levodopa for Residual Amblyopia
Intervention: 16 weeks while patching 2h/d
oral levodopa (oral levodopa 0.76 mg/kg with carbidopa 0.17
mg/kg ) vs placebo TID
Results: at 18 weeks
Levodopa = placebo (5.2 vs 3.8 letters=not statistically
significant)
No adverse effect from levodopa
AP Santiago MD 2015
48. Amblyopia Treatment Study-18 (ATS-18)
Binocular Computer Activities for Treatment of Amblyopia
REVIEW of LITERATURE
Li J, Thompson B, Deng D, Chan LY, Yu M, Hess RF. Dichoptic training enables the adult 1080
amblyopic brain to learn. Curr Biol 2013;23:R308-9. 1081
Hess RF, Thompson B, Black JM, et al. An iPod treatment of amblyopia: an updated 1082 binocular
approach. Optometry 2012;83:87-94. 1083
To L, Thompson B, Blum JR, Maehara G, Hess RF, Cooperstock JR. A game platform for 1084
treatment of amblyopia. IEEE Trans Neural Syst Rehabil Eng 2011;19:280-9. 1085
Li SL, Jost RM, Morale SE, et al. A binocular iPad treatment for amblyopic children. Eye (2014) 28,
1246–1253; doi:10.1038/eye.2014.165; published online 25 July 2014.
Li SL, Jost RM, Morale SE, et al. Binocular iPad Treatment of Amblyopia for Lasting Improvement of
Visual Acuity. JAMA Ophthalmol. 2015;133(4):479-480. doi:10.1001/jamaophthalmol.2014.5515.
Birch EE, Li S, Jost RM, et al. Binocular iPad treatment for amblyopia in preschool 1088 children. J
AAPOS 2014 AAPOS. 1089
AP Santiago MD 2015
49. Amblyopia Treatment Study-18 (ATS-18)
Binocular Computer Activities for Treatment of Amblyopia
Ended May 2, 2016
To compare the effectiveness of 1 hour/day of binocular game
play 7 days per week (minimum of 4 days per week) with 2
hours/day of patching 7 days per week, in children 5 to <13 years
of age (younger cohort), as a non-inferiority study.
To compare the effectiveness of 1 hour/day of binocular game
play 7 days per week (minimum of 4 days per week) with 2
hours/day of patching 7 days per week, in children 13 to <17
years of age (older cohort), as a superiority study.
AP Santiago MD 2015
50. Lessons learned from PEDIG Studies
1. Atropine = patching
2. 6 hours = full time
3. 2 = 6 hours
4. Amblyopia improves with glasses alone.
5. Add patching after glasses given time to work.
AP Santiago MD 2015
51. Lessons learned from PEDIG Studies
6. Spectacles and patching even for 13-17.
7. Daily = weekly
8. Near = Far
9. Severe amblyopia can improve even with 2 h of patching
10. Bangerter filter = patching
AP Santiago MD 2015
52. Lessons learned from PEDIG Studies
11. Intensive final push with atropine and patch not effective.
12. Levodopa promising but same as placebo.
13. 6h >2h: Increasing 2 to 6 hours can improve amblyopia
(if plateau with 2 hours reached).
14. Plano lenses don’t work.
AP Santiago MD 2015
53. Every closed eye is not sleeping, and every
open eye is not seeing.
-- Bill Cosby