2016 amblyopia pedig studies

Amblyopia Treatment Studies Pediatric Eye Disease Investigator Group 2002-2016 (Publications as of September 13, 2016)

Alvina Pauline D. Santiago, MD

September 2016

http://pedig.jaeb.org/Studies.aspx

http://www.abcd-vision.org/amblyopia/ats-pedig.html

AP Santiago MD 2016

http://talleyeyecare.com

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



  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



  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



  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



  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



  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



  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



  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/

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

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 2015http://oceansignal.com

http://oceansignal.com

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://upload.wikimedia.org

http://oceansignal.com

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

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



  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



  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


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

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


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

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

✚


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


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

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

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


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

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

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

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

http://www.clipartbest.com


  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

http://www.clipartbest.com


  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

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

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

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


  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



  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


  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


  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


  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

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

  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)

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

  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 �


3 to <8, 20/50 to 20/400

  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 �


3 to <8, 20/50 to 20/400

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

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

What more PEDIG?

http://www.imore.com

http://www.geek.com

http://www.cclonline.com/

http://icons.iconarchive.com AP Santiago MD 2015

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

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

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


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


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

Every closed eye is not sleeping, and every open eye is not seeing.

-- Bill Cosby

2016 amblyopia pedig studies

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