Study of Binocular Computer Activities for Treatment of Amblyopia

The purpose of the study is to 1) 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 patching 7 days per week,
in children 5 to <13 years of age (younger cohort), as a non-inferiority study; and 2) 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 patching 7 days per week, in children 13 to <17 years of age
(older cohort), as a superiority study.

Inclusion Criteria:

1. Age 5 to <17 years

2. Amblyopia associated with strabismus, anisometropia, or both (previously treated or
untreated)

1. Criteria for strabismus: At least one of the following must be met:

- Presence of a heterotropia on examination at distance or near fixation (with
or without spectacles)

- Documented history of strabismus which is no longer present (which in the
judgment of the investigator could have caused amblyopia)

2. Criteria for anisometropia: At least one of the following criteria must be met:

- ≥0.50 diopter (D) difference between eyes in spherical equivalent

- ≥1.50 D difference between eyes in astigmatism in any meridian

3. Criteria for combined-mechanism amblyopia: Both of the following criteria must be
met:

- Criteria for strabismus are met (see above)

- ≥1.00 D difference between eyes in spherical equivalent OR ≥1.50 D
difference between eyes in astigmatism in any meridian

- Note: the spherical equivalent requirement differs from that in the
definition for refractive/anisometropic amblyopia

3. No amblyopia treatment in the past 2 weeks (patching, atropine, Bangerter, vision
therapy)

4. Refractive correction (spectacles or contact lenses, if applicable) must meet the
following criteria at enrollment and be based on a cycloplegic refraction that is not
more than 7 months old.

1. Requirements for Correction of Refractive Error:

1. For subjects meeting criteria for strabismic (only) amblyopia (see 2.2.1 #2
above):

• Hypermetropia, if corrected, must not be under-corrected by more than
+1.50 D spherical equivalent, and the reduction in plus sphere must be
symmetric in the two eyes.

2. For subjects meeting criteria for anisometropic or combined-mechanism
amblyopia (see 2.2.1 #2 above):

- Spherical equivalent must be within 0.50 D of fully correcting the
anisometropia

- Hypermetropia must not be under-corrected by more than +1.50 D
spherical equivalent, and reduction in plus must be symmetric in the
two eyes

- Cylinder power in both eyes must be within 0.50 D of fully correcting
the astigmatism

- Cylinder axis for both eyes must be within 6 degrees of the axis of the
cycloplegic refraction when cylinder power is ≥1.00 D

2. Refractive corrections meeting the above criteria must be worn for either:

- 16 weeks or more or

- Until visual acuity in amblyopic eye is stable (defined as 2 consecutive
visual acuity measurements by the same testing method at least 4 weeks apart
with <1 line change (<5 letters if E-ETDRS))

3. Monocular or binocular contact lens wear is allowed provided the contact lenses
meet the above refractive requirements at the corneal plane. The same form of
correction must be worn throughout the entire study during study procedures
(i.e., no changing between contacts and spectacles while patching or while
game-playing or study testing). Safety glasses are not required for subjects
wearing contact lenses, but investigators are encouraged to suggest safety
glasses be worn over contact lenses.

5. Visual acuity, measured in each eye without cycloplegia in current refractive
correction (if applicable) within 7 days prior to randomization using the Amblyopia
Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children <
7 years and the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual
acuity protocol for children ≥ 7 years on a study-approved device displaying single
surrounded optotypes, as follows:

1. Visual acuity in the amblyopic eye 20/40 to 20/200 inclusive (33 to 72 letters if
E-ETDRS)

2. Visual acuity in the fellow eye 20/25 or better (≥ 78 letters if E-ETDRS)

3. Interocular difference ≥ 3 logMAR lines (≥ 15 letters if E-ETDRS) (i.e.,
amblyopic-eye acuity at least 3 logMAR lines worse than fellow-eye acuity)

6. Heterotropia or heterophoria with a total near deviation of ≤ 10∆ (measured by PACT).

7. Ability to align the nonius cross on the binocular game system (angles of ocular
deviation >10∆ would require the nonius cross to be adjusted to such an extent that
playing of the game would be compromised).

8. Subject is able to play Hess Falling Blocks game on the study iPad® (on easy setting)
under binocular conditions (with red-green glasses), as demonstrated by scoring at
least 1 line in the office.

9. Investigator is willing to prescribe computer game play or patching per protocol.

10. Parent understands the protocol and is willing to accept randomization.

11. Parent has phone (or access to phone) and is willing to be contacted by Jaeb Center
staff.

12. Relocation outside of area of an active Pediatric Eye Disease Investigator Group
(PEDIG) site for this study within the next 16 weeks is not anticipated.

Exclusion Criteria:

A subject is excluded for any of the following reasons:

1. Prism in the refractive correction at time of enrollment (eligible only if prism is
discontinued 2 weeks prior to enrollment).

2. Myopia greater than -6.00 D spherical equivalent in either eye.

3. Previous intraocular or refractive surgery.

4. Any treatment for amblyopia (patching, atropine, Bangerter filter, or vision therapy)
during the past 2 weeks. Previous amblyopia therapy is allowed regardless of type, but
must be discontinued at least 2 weeks immediately prior to enrollment.

5. Ocular co-morbidity that may reduce visual acuity determined by an ocular examination
performed within the past 7 months (Note: nystagmus per se does not exclude the
subject if the above visual acuity criteria are met).

6. No Down syndrome or cerebral palsy

7. No severe developmental delay that would interfere with treatment or evaluation (in
the opinion of the investigator). Subjects with mild speech delay or reading and/or
learning disabilities are not excluded.

8. Heterotropia or heterophoria with a total ocular deviation >10∆ (phoria plus tropia
>10∆) at near (measured by PACT).