Download - 2014 pedig amblyopia studies

Amblyopia Treatment

StudiesPediatric Eye Disease Investigator Group

2002-2013(Publications as of July 2014)

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

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

Amblyopia Treatment Study-1 (ATS-01)

Atropine vs part-time patch, moderate amblyopia

n I. Arch Ophthalmol 2002: 120(3) 268-278n II. Arch Ophthalmol 2002: 120 (3) 281-287n III. Arch Ophthalmol 2003: 121 (11): 1625-32n IV. Arch Ophthalmol 2005: 123 (2): 149-157n V. J AAPOS 2005: 9 (6): 542-545n VI. Arch Ophthalmol 2008: 1039-1044



n I. Arch Ophthalmol 2002: 120(3) 268-278n VA 20/40-20/100n 3 or more lines:

n Atropine (74%) & Patching (79%)n Atropine & patching similar for age 3-7 yrn Atropine better acceptability



n II. Arch Ophthalmol 2002: 120 (3) 281-287n Clinical profile of moderate amblyopia

subjectsn moderate amblyopia 20/40-20/100n 7 yrs and belown Same effect for strabismic and

anisometropic amblyopia



n III. Arch Ophthalmol 2003: 121 (11): 1625-32n Impact of patching vs atropinen Both well tolerated by child and familyn Atropine more favorable



n IV. Arch Ophthalmol 2005: 123 (2): 149-157n 2 yr follow up after 6 month of patching

or atropinen Similar results in both groupsn Amblyopic eye still 2 lines worse than

sound eye


Atropine vs part-time patch, moderate amblyopian V. J AAPOS 2005: 9 (6): 542-545

n Effect of amblyopia tx on ocular alignmentn Same rates of deterioration or

improvement in both groupsn New strabismus by 2 yrs: most resolved

after cessation of treatmentn 18% in patching: 2 greater than 8PDn 16% in atropine: 3 greater than 8PD



n VI. Arch Ophthalmol 2008: 1039-1044n 10 year follow up

n improvement of amblyopia maintainedn Outcome similar for both groupsn residual amblyopia common

n treatment initiated at age 3-7 years


n I. Ophthalmology 2003: 110(11) 2075-2087n II. Arch Ophthalmol 2003: 121 (5) 603-611n III. J AAPOS 2004: 8(5): 420-428

Amblyopia Treatment Study-2A (ATS-2A)

Patch 6 hrs vs full time, severe amblyopia

n I. Ophthalmology 2003: 110(11) 2075-2087n Full time: all waking hrs minus 1 hour offn Severe amblyopia: 20/100-20/400n Age 3-7 yearsn After 4 months

n 4.8 lines in 6 hrs group; vs 4.7 in full time

Amblyopia Treatment Study-2B (ATS-2B)

Patch 2 hrs (minimal time) vs 6 hrs (part time)for Moderate amblyopia

n II. Arch Ophthalmol 2003: 121 (5) 603-611n moderate: 20/40-20/80n ages 3-7 yearsn At 4 months: 2.4 lines in both groups

with 1 hr of near visual activity

Amblyopia Treatment Study-2C (ATS-2C)

Recurrence after cessation of patching / Atropinen III. J AAPOS 2004: 8(5): 420-428

n younger than age 8n 3 months of amblyopia treatmentn Recurrence same

n 24% of patched patients; 21% of atropinizedn 1/4 experience recurrence within 1st year of

cessationn RCT for weaning vs. no-weaning


7 to < 18: spectacles vs atropine/patch

n Arch Ophthalmol 2005: 123: 437-477 (Control)

n Am J Ophthalmol 2004: 137: 581-583 (10-18yrs)

n Arch Ophthalmol 2007: 125: 655-659



n Pediatric Eye Disease Investigator Group. Randomized trial of treatment of amblyopia in children aged 7 to 17 years. Arch Ophthalmol 2005;123:437-47.

n Pediatric Eye Disease Investigator Group. Stability of visual acuity improvement following discontinuation of amblyopia treatment in children aged 7 to 12 years. Arch Ophthalmol 2007;125:655-9.



n ages 7-17 yearsn 20/40-20/400

n Given optimal optical correction then randomizedn Tx: glasses, patch plus near activity,

atropinen No Tx: glasses alone



n Responders: improved by >/= 10 letters / 2 linesn Amblyopia improves with Rx alone in 25%n Most patients left with residual VA deficitn Ages 7-12: tx improved amblyopia even if

previously treatedn Ages 13-17: tx improved if no previous tx for

amblyopian Unknown: if treatment results robust (if it will

stay)


Atropine weekend vs daily; moderate amblyopia

n Ophthalmology 2004: 111: 2076-2085n 20/40-20/80n ages 3-7 yearsn Similar results with weekend atropine vs

daily atropinen 2.3 lines in both groups


3 to < 7, spectacles alone vs patch 2 hrs + spectacles

n Ophthalmology 2006: 113 (6) 895-903.n amblyopia improved with Rx by >/= 2

lines in 77%n amblyopia resolved in 27% with Rx alonen 3 line improvement averagen Lessen the burden of amblyopia therapy


3 to <7, spectacles alone, then patch 2 hrs vs spectacles

n Ophthalmology 2006: 113 (6) 904-912.n Strabismic and anisometropic amblyopian 20/40-20/400n 2 hrs (1 hr near activity) + specs vs.

specs alone


spectacles alone, then patch 2 hrs vs spectacles

n Ophthalmology 2006: 113 (6) 904-912.n 5 wks: 1.1 lines treated; 0.5 lines specsn Any visit average: 2.2 lines treated; 1.1

lines specsn After glasses, 2 hrs patching (with 1 hr

near activity) improves moderate to severe amblyopia


3 to <7, patch 2 hrs with near vs far activities after spectacles

n J AAPOS 2005: 9: 129-136n Pilot: 4 wks: suggestion of greater

improvement in amblyopic eye with near activities prescribed

n 2.6 lines near; 1.6 lines far (p=0.07)



(VA 20/40 to 20/400)n Ophthalmology 2008; 115: 2071-78

n At 8 wks: improvement in amblyopic eyen Distance activity: 2.6 linesn Near activity: 2.5 lines 2.6 lines near;

1.6 lines far (p=0.07)n Similar for both groups, even at 2, 5,

17 wks.



(VA 20/40 to 20/400)n Ophthalmology 2008; 115: 2071-78

n 3.6 lines improvement in severe amblyopic group

n Near activities do not improve VA outcome in anisometropic, strabismic, combined amblyopia with 2 hrs of daily patching

n Severe amblyopia can respond even to 2 hrs of daily patching


Bilateral refractive amblyopia; specs x 1 yr(Response to treatment of previously untreated

presumed bilateral refractive amblyopia)n Am J Ophthalmol 2007: 144: 487-496

n 20/40-20/400n less than 10 yearsn Hypermetropia >/= 4.0D; astigmatism

>/= 2.0Dn Eyeglasses alone improves binocular VA

to 20/25 or better within 1 year


3 to <7, atropine vs Atropine plus plano lens to sound eye

n Arch Ophthalmol 2009;127(1):22-30

n Moderate amblyopia .20/40-20/100n Weekend atropine plus plano lens =

atropine alone


(7 to <13, ATS-1: weekend atropine vs. patch 2hoursn Patching vs atropine to treat amblyopia in children aged 7

to 12 years: a randomized trial. Arch Ophthalmol. 2008;126(12):1634-1642

n Age 7-12; moderate amblyopia 20/40-20/100n 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.

n Atropine and patching achieve similar results among older children with unilateral amblyopia


Bangerter filters vs. patching

n A randomized trial comparing Bangerter filters and patching for the treatment of moderate amblyopia in children. Ophthalmology 2010;117:998-1004. |

n moderate amblyopia 20/40-20/80; 3-<10y.

n At 24 wks, 1.9 lines improvement with Bangerter, vs.2.3 lines in patching group

n 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.

ATS 11: A randomized trial to evaluate combined patching-atropine treatment for

residual amblyopian Evaluate effectiveness of treatment of residual amblyopia

in 3-10yn VA 20/32 to 20/63 (mild residual amblyopia)n RCT: intensive treatment vs. rapid weaning plus glasses

n 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.


residual amblyopia

n The study was stopped on recommendation of the data and safety monitoring committeen slow recruitment n conditional power analysis indicating that the

study was unlikely to find a statistically significant benefit


residual amblyopia

n Intensive final push of combined treatment with patching and daily atropine did not produce a better visual acuity outcome after 10 weeks

n Compared with a control group in whomtreatment was gradually discontinued

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

n Terminatedn Awaiting publication of results

n 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.

ATS 13: An Observational Study of Optical Correction for Strabismic Amblyopia in Children 3 to < 7 years old

n Optical Treatment of Strabismic and Combined Strabismic Anisometropic Amblyopia. Ophthalmology 2012; 119: 150-158. Epub 2011 Sep 29.

n VA after 18 weeks improved mean of 2.6 lines

n 75% >/= 2 line, 54% >/= 3 lines

n Resolution of amblyopia in 32%

n Greater in Strabismic Amblyopia alone (3.2 vs 2.3 lines)

n VA improved regardless of whether alignment better

n Optical treatment alone results in clinically meaningful improvement; may consider as primary sole initial treatment for this group

ATS 14: A Pilot Study to evaluate levodopa as treatment for residual amblyopia in 8-17 years old

n 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.


n At the time of enrollment, subjects were required to have been treated with at least 2 hours per day of daily patching

n And stable visual acuity n defined as less than 5 letters or one

logMAR line of improvement since a previous visit at least 8 weeks earlier.


n Intervention: n continuing 2 hours of daily patchingn 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).


n Intervention: n The study medication was administered for 8

weeks with one additional week for tapering of treatment.

n Levodopa was prepared in capsules combined with carbidopa 0.17 mg/kg/tid.

n Carbidopa was combined with levodopa to reduce side-effects associated with levodopa alone.


n The mean improvement in amblyopic eye in 9-week primary outcome visit was

n +4 (±4) letters in the 16 subjects in the lower dose group and

n +6 (±6) letters in the 17 subjects in the higher dose group


n An improvement of 10 or more letters noted in 2 (13%) in low dose, and 5 (29%) in high dose group at 9 wks

n Fellow eye improved 1 letter in high dose and zero letter is low dose group

n Justification: Small sample, experience with drug, promising result

ATS 15: Increasing patching for amblyopia study from 2 hours to 6 hours,

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

n 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

ATS 16: Augmenting atropine treatment for amblyopia in 3 to <8, 20/50 to 20/400 with

plano lens to sound eye(Closed Aug 2013)

n Objective:This study is designed to evaluate the effectiveness of adding a plano lens to weekend atropine after visual acuity has stabilized with weekend atropine but amblyopia is still present.

n 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,

n 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.

n The primary objective is to determine if adding a plano lens to weekend atropine will improve visual acuity in patients with amblyopia still present after visual acuity has stabilized with initial treatment.

ATS 17A: Randomized trial of levodopa as treatment for residual amblyopia

(Closed Oct 2013)

n Primary Objective:

n The primary objective of the study is to compare the efficacy and safety of oral levodopa and patching versus oral placebo and patching at 18 weeks, after 16 weeks of treatment for amblyopia in children 7 to <13 years old followed by a two-week taper of oral medication.

n Secondary Objectives:

n To evaluate maximum improvement in visual acuity with oral levodopa plus patching versus oral placebo plus patching through 26 weeks.

n To evaluate the frequency of recurrence of amblyopia after 13 weeks of no therapy, among subjects from both randomized treatment groups who have improved from baseline by 10 or more letters in amblyopic eye visual acuity at 26 weeks and are ready to stop amblyopia treatment.