Dichoptic Video Treatment for Amblyopia in Children Age 3-7 Years
Phase: NA
Conditions: Amblyopia
Sponsor: Retina Foundation of the Southwest

Protocol Title: Randomized Clinical Trial of Streaming Dichoptic Movies versus 
Patching for Treatment of Amblyopia in Children Aged 3 to 7 Years 
 
Date: January 31, 2019 
 
clincaltrials.gov identifier: NCT03825107 
 
Financial support: National Institutes of Health Grant EY022313 (Birch, PI) 
Principal Investigator:  
Eileen E Birch, PhD 
 
 
 
 
Senior Research Scientist 
 
 
 
 
Pediatric Vision Laboratory 
 
 
 
 
Retina Foundation of the Southwest 
 
 
 
 
9600 North Central Expressway, Suite 200 
 
 
 
 
Dallas, TX 75231  
 
 
 
 
phone: (214) 363-3911 
 
 
 
 
email: ebirch@retinafoundation.org 
 
Single site study conducted at: Retina Foundation of the Southwest 
 
 
 
 
 
9600 North Central Expressway, Suite 200 
 
 
 
 
 
Dallas, TX 75231  
 
 
 
Project Summary 
Contrast-rebalanced dichoptic movies (with fellow eye contrast reduced) have been 
shown to be an effective binocular treatment for amblyopia in a laboratory setting. Yet, 
at-home therapy is a more practical approach. While contrast-rebalanced binocular 
tablet games have been shown to be an effective at-home treatment for amblyopia, the 
games can be challenging for some of the youngest children with amblyopia. To 
address this need, we will compare dichoptic movies, streamed at-home on a handheld 
3D-enabled game console, versus patching as amblyopia treatment for children aged 3 
to 7 years with amblyopia. The primary outcome will be change in best-corrected acuity 
at the 2-week visit in children treated with streaming dichoptic movies versus children 
treated with standard-of-care 2 hours/day patching. A secondary objective is to 
determine whether amblyopic eye visual acuity improvement at the 2-week visit is 
significant in each of the treatment groups. Fifty-six amblyopic children (aged 3-7 years) 
will be randomly assigned to patching (2 hours/day, 7 days/week; 28 hours total) or 
binocular treatment (3 dichoptic movies per week; 9 hours total). In the context of prior 
amblyopia treatment results with at-home contrast-rebalanced tablet games and with in-
lab contrast-rebalanced movies, we anticipate that dichoptic movies, streamed at-home 
on a handheld 3D-enabled game console will be more effective than patching. 
 
Rationale and background 
Contrast-rebalanced binocular tablet games (with fellow eye contrast reduced) have 
been shown to be an effective treatment for amblyopia.1,2 However, the games can be 
challenging for some of the youngest children and boring for some of the older children 

with amblyopia. To provide additional treatment options using the same contrast-
rebalancing approach, we have processed animated videos to allow dichoptic viewing, 
with full contrast for the amblyopic eye and reduced contrast for the fellow eye. In 
prospective single-arm studies, contrast-rebalanced dichoptic movies have been used 
as an effective treatment for children aged 4 to 12 years with amblyopia.3 With as little 
as 9 hours of viewing time, mean improvement of visual acuity of the amblyopic eyes 
was 1.5 to 2.0 lines.4,5 There is evidence that younger children (<7 years) are more 
responsive to amblyopia treatments,6,7 including treatment with contrast-rebalanced 
dichoptic movies, than older children.4 While in-lab studies of amblyopia treatment with 
contrast-rebalanced dichoptic movies provided proof-of-principle data for the treatment 
approach, at-home treatment is a more practical alternative.  
 
Study Goal 
To explore an at-home amblyopia treatment in younger children with contrast-
rebalanced dichoptic movies. 
 
Objective 
In a randomized clinical trial, we plan to evaluate the effectiveness of viewing cloud-
based contrast-rebalanced dichoptic movies streamed on a handheld device in children 
aged 3 to 7 years compared with standard-of-care patching treatment.8 
 
Methodology 
Children aged 3 to 7 years who are diagnosed by pediatric eye specialists as having 
amblyopia due to strabismus, anisometropia, or both (combined mechanism) are 
eligible. Diagnoses, alignment, prior treatment, and visual acuity for visits prior to 
enrollment will be extracted from the referring doctor’s medical records.  
 
Inclusion criteria 
-Amblyopic eye visual acuity of 0.2 to 0.8 logMAR 
-Fellow eye visual acuity of -0.1 to 0.2 logMAR 
-Interocular visual acuity difference of >0.2 logMAR 
-Anisometropia or corrected strabismus (<5pd) 
-Wearing glasses for at least 8 weeks with no change in visual acuity over two visits 
-Must be able to see the full movie screen (both amblyopic and fellow eye components) 
with fellow eye contrast set to 20%.  
 
Exclusion criteria 
-Prematurity of 8 weeks or more 
-Coexisting ocular or systemic disease 
-Developmental delay 
-Significant ocular misalignment (>=5 pd).  
 
Study Design 
This study is a randomized clinical trial (parallel group design). At the baseline visit, 
eligibility will be ascertained and vision assessments conducted. Children will be 
randomly assigned to watch contrast-rebalanced dichoptic animated movies 

(experimental treatment) or to patch the fellow eye 2 hours/day every day (standard-of-
care amblyopia treatment) for 2 weeks. Randomization will performed through the 
website www.randomization.org with a coded distribution of a 1:1 ratio, with blocks of 12 
allocations. Investigators will have access to the randomization assignment (sealed in a 
numbered envelope) only after the child is enrolled.  
 
At the 2-week primary outcome visit, children in the patching group will cross over to the 
dichoptic animated movie group and all participants will be asked to return for a 
secondary outcome visit vision assessment at 4 weeks. After that, children in the 
dichoptic movie group will have the option to continue an additional 2 weeks and 
children who were initially in the patching group will have the option to continue with 
movies for an additional 4 weeks (up to 6 weeks of movies for both groups). Children 
who continue will have follow-up visits with vision assessments every 2 weeks (14±3 
days). 
 
Dichoptic Movies 
Eighteen popular animated feature films were modified using custom MATLAB software 
to allow dichoptic presentation on a New Nintendo 3DS XL platform (Nintendo 
Corporation, Kyoto, Japan), which will be loaned to the child for the duration of the study  
so that movies can be watched at home. This Nintendo device allows for dichoptic 
viewing without the need for anaglyphic, polarized, or shutter glasses or a VR headset.  
The movies have the same design as in our recent prospective study of contrast-
rebalanced movies in which children came into the laboratory to watch movies on a 
passive 3D display.4,5 Briefly, odd lines in the Nintendo 3D display are visible to one 
eye, and even lines are visible to the other eye. A patterned image mask composed of 
irregularly shaped blobs was multiplied with the images seen by the amblyopic eye, and 
the inverse patterned mask was multiplied with the images seen by the fellow eye, so 
that different parts of the display are seen by each eye. Blobs of the movie seen by the 
amblyopic eye always have high contrast (100%), whereas the complementary blobs 
seen by the fellow eye have reduced contrast. Because the blobs had Gaussian edges, 
the edges of the blobs overlap and are seen by both eyes with differing contrasts, 
preventing any significant rivalry. The shape and location of the blobs are varied 
dynamically every 10 seconds. Fellow eye contrast starts at 20% for the first movie and 
increments by 10% for each subsequent movie (i.e., 20%, 22%, 24%, 26%, 29%, …). 
Movies have been uploaded to our Amazon Web Services (AWS; Seattle, WA, USA) 
streaming service in two-week packets, each containing 6 movies that preserve the 
order of fellow eye contrasts from low to high. 
 
Study Protocol 
Children allocated to the dichoptic movie arm will be asked to watch 3 movies per week 
(about 4.5 hours per week) during each 2-week period. During their visit, we will provide 
a link on their loaned Nintendo for the set of 6 movies that should be watched during the 
next two weeks. Movie names are numbered on the Nintendo device, in order by fellow 
eye contrast, and the family will be instructed that the movies should be viewed in that 
order at home with the date recorded on a paper calendar. Fellow eye contrast of 
movies 1-6 increment from 20% to 32% during the first 2 weeks, movies 7-12 increment 

from 35% to 57% during weeks 3 and 4 and, finally, movies 13-18 increment from 63% 
to 100% if children participate in the optional weeks 5 and 6.  Children allocated to the 
patching arm will be supplied with patches and asked to patch two hours per day for two 
weeks. At the 2-week visit, children in the patching group will be loaned a Nintendo and 
begin watching movies, starting with 20% fellow eye contrast for the next two weeks, 
and have the option of completing up to 6 weeks of movies. 
 
Vision Assessments 
Visual acuity.  Crowded monocular best-corrected visual acuity (BCVA) will be tested at 
each visit using the Amblyopia Treatment Study HOTV protocol for 3- to 6-year olds9-11 
and the E-ETDRS protocol for 7-year olds.12,13   
 
Stereoacuity. Stereoacuity will be assessed with the Randot Preschool Stereoacuity 
Test and the Stereo Butterfly Test; stereoacuity will be converted to log arcsec for 
analyses; nil stereoacuity will be arbitrarily assigned a value of 4.0.14 
 
Suppression.  Extent of suppression will be assessed using the Worth-4 dot test at 7 
distances (3m, 2m, 1m, 0.67m, 0.5m, 0.33 m, and 0.16m); the farthest distance at which 
the child reports 4 dots will be converted to the area of suppression scotoma in log 
degrees. 15 Depth of suppression will be evaluated using a dichoptic eye chart that 
identifies the non-preferred eye/preferred eye contrast ratio (i.e., balance point) at which 
the child can overcome suppression and report letters presented to each eye with equal 
likelihood (Contrast Balance Index; CBI).16,17   
 
Sample Size  
 
Based on our recent prospective study of contrast re-balanced dichoptic movies as a 
treatment for amblyopia,4,5  we anticipate a 0.15±0.10 logMAR (7.5 letters) improvement 
in visual acuity at the 2-week primary outcome visit for children assigned to the 
dichoptic movie arm.  For children assigned to the patching group, we anticipate a 
0.07±0.10 logMAR (3.5 letters) improvement at 2 weeks based on results from our prior 
study of patching versus a contrast-rebalanced dichoptic game as a treatment for 
amblyopia.2 With these expected means, a sample size of 28 per group (56 total) will 
provide 85% power to declare that the two groups have significantly different means, 
using a two-sided p-value of less than 0.05. We will enroll and randomize 62 children 
(31 per group) to account for potential 10% loss to follow-up. 
 
 
Expected Outcomes 
Results will be disseminated at the annual meetings of the Association for Pediatric 
Ophthalmology & Strabismus and the Association for Research in Vision & 
Ophthalmology and submitted for publication in a leading medical/scientific journal.  
 
If this novel at-home binocular movie treatment is effective in improving amblyopic eye 
visual acuity, it will provide an additional treatment option for amblyopia in young 
children. 

 
References 
 
1 
Birch, E. E. et al. Binocular iPad treatment for amblyopia in preschool children. J AAPOS 
19, 6-11, doi:10.1016/j.jaapos.2014.09.009 (2015). 
2 
Kelly, K. R. et al. Binocular iPad game vs patching for treatment of amblyopia in children: 
A randomized clinical trial. JAMA Ophthalmol 134, 1402-1408, 
doi:10.1001/jamaophthalmol.2016.4224 (2016). 
3 
Birch, E. et al. Binocular amblyopia treatment with contrast re-balanced movies. Journal 
of AAPOS in press (2019). 
4 
Birch, E. E. et al. Binocular amblyopia treatment with contrast-rebalanced movies. J 
AAPOS 23, 160 e161-160 e165, doi:10.1016/j.jaapos.2019.02.007 (2019). 
5 
Li, S. L. et al. Dichoptic movie viewing treats childhood amblyopia. J AAPOS 19, 401-405, 
doi:10.1016/j.jaapos.2015.08.003 (2015). 
6 
Holmes, J. M. et al. Effect of age on response to amblyopia treatment in children. Arch 
Ophthalmol 129, 1451-1457, doi:10.1001/archophthalmol.2011.179 (2011). 
7 
Lasker/IRRF Initiative for Innovation in Vision Science. Amblyopia: Challenges and 
opportunities. Vis Neurosci 35, E010 (2018). 
8 
Ophthalmology, A. A. o. Pediatric Eye Evaluations PPP - 2017, 
<https://www.aao.org/preferred-practice-pattern/pediatric-eye-evaluations-ppp-2017> 
(2017). 
9 
Moke, P. S. et al. Computerized method of visual acuity testing: adaptation of the 
amblyopia treatment study visual acuity testing protocol. Am J Ophthalmol 132, 903-909 
(2001). 
10 
Holmes, J. M. et al. The amblyopia treatment study visual acuity testing protocol. Arch 
Ophthalmol 119, 1345-1353, doi:10.1001/archopht.119.9.1345 (2001). 
11 
Drover, J. R. et al. Normative pediatric visual acuity using single surrounded HOTV 
optotypes on the Electronic Visual Acuity Tester following the Amblyopia Treatment 
Study protocol. J AAPOS 12, 145-149, doi:10.1016/j.jaapos.2007.08.014 (2008). 
12 
Beck, R. et al. A computerized method of visual acuity testing: adaptation of the early 
treatment of diabetic retinopathy study testing protocol. Am J Ophthalmol 135, 194-205 
(2003). 
13 
Cotter, S. et al. Reliability of the electronic early treatment diabetic retinopathy study 
testing protocol in children 7 to <13 years old. Am J Ophthalmol 136, 655-661 (2003). 
14 
Birch, E. et al. Randot Preschool Stereoacuity Test: normative data and validity. J AAPOS 
12, 23-26, doi:10.1016/j.jaapos.2007.06.003 (2008). 
15 
Rosenbaum, A. L. & Santiago, A. P. Clinical strabismus management : principles and 
surgical techniques.  (Saunders, 1999). 
16 
Birch, E. E. et al. Assessing suppression in amblyopic children with a dichoptic eye chart. 
Invest Ophthalmol Vis Sci 57, 5649-5654, doi:10.1167/iovs.16-19986 (2016). 
17 
Webber, A. L., Wood, J. M., Thompson, B. & Birch, E. E. From suppression to 
stereoacuity: a composite binocular function score for clinical research. Ophthalmic 
Physiol Opt 39, 53-62, doi:10.1111/opo.12599 (2019).