Seminars in Ophthalmology

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/isio20

Emerging therapies for amblyopia

Michelle M. Falcone, David G. Hunter & Eric D. Gaier

To cite this article: Michelle M. Falcone, David G. Hunter & Eric D. Gaier (2021): Emerging
therapies for amblyopia, Seminars in Ophthalmology, DOI: 10.1080/08820538.2021.1893765

To link to this article: https://doi.org/10.1080/08820538.2021.1893765

Published online: 03 Mar 2021.

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SEMINARS IN OPHTHALMOLOGY
https://doi.org/10.1080/08820538.2021.1893765

REVIEW

Emerging therapies for amblyopia

Michelle M. Falconea,b, David G. Huntera,b, and Eric D. Gaiera,b,c
a
Department of Ophthalmology, Boston Children’s Hospital, Boston, United States; bDepartment of Ophthalmology, Harvard Medical School, Boston,
United States; cPicower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology,
Cambridge, United States

ABSTRACT ARTICLE HISTORY

Traditional therapies to treat amblyopia, such as optical correction or occlusion/penalization of the non- Received 28 January 2021
amblyopic eye, are efficacious but are not without limitations such as poor adherence and decreased Accepted 29 January 2021
success with increasing age. Recently, there has been an interest in new amblyopia therapies, some using KEYWORDS
binocular techniques, through a variety of platforms including video games, movies, and virtual reality. Amblyopia; Perceptual
Overall, available efficacy results for these treatments are highly variable. learning; Binocular therapy;
Dichoptic therapy; Virtual
reality

INTRODUCTION
Amblyopia is the leading cause of monocular vision impair­ resolution of amblyopia with optical treatment alone occurs
ment in children and adults.1 It is defined as a reduction of in 32% of patients, and the remaining patients require
best-corrected visual acuity that results from abnormal proces­ additional therapy with penalization of the sound eye either
sing of visual images early in life that cannot be attributed to in conjunction with spectacle correction or sequentially
structural abnormalities of the eye or visual pathway.2 It is with incomplete resolution after optical treatment.2,11,12
most commonly unilateral, though it can be bilateral.3 Occlusion and penalization of the sound eye has been the
Though the prevalence of amblyopia in individuall a studies gold standard treatment for unilateral amblyopia since 1743.7
varies based on definition, the pooled prevalence was recently In children <7 years old, patching 2 hours per day compared to
estimated to be around 1.5%.4,5 Amblyopia is classified accord­ 6 hours per day results in similar improvements in visual acuity
ing to the underlying cause and can be strabismic, refractive, or in moderate amblyopia, and patching 6 hours per day com­
deprivational.2 pared to full-time patching leads to similar improvement in
If recognized and treated early, vision loss secondary to visual acuity in severe amblyopia.13,14 In children 13 to 17 years
amblyopia can be reversible. Traditional therapies for amblyopia old with treatment-naïve amblyopia, patching may improve
include correction of refractive errors, patching, and atropine visual acuity.15 One of the barriers to successful patching is
penalization. In children with deprivational amblyopia, surgery treatment adherence. Young children, children with develop­
and refractive rehabilitation are also necessary.2 While these mental delays, or children with severe amblyopia may not
traditional therapies have been well studied and are efficacious, tolerate patching. Children who use a cloth patch over specta­
their limitations include poor adherence and decreased treat­ cles may find a way to peek around it. Patching carries a stigma
ment success with increasing age.6 In this article, we will review and consequential psychosocial impact that may dissuade older
traditional amblyopia therapies and discuss new therapies being children from adhering to their prescribed treatment.
used to treat amblyopia, particularly binocular treatments. Optical penalization of the non-amblyopic eye with
atropine drops via its cycloplegic effect has been used as
an alternative to patching.2 In a PEDIG study of children
TRADITIONAL AMBLYOPIA THERAPIES <7 years with strabismic or anisometropic amblyopia ran­
Traditional amblyopia therapies include optical treatment domized to receive either patching or atropine, visual
and penalization of the sound eye.7,8 Correcting refractive acuity improved substantially in both groups and at
error alone can improve visual acuity in both refractive and 6 months, there was no difference in visual acuity out­
strabismic amblyopia.9–11 The Pediatric Eye Disease comes between treatment groups; however, the patching
Investigator Group (PEDIG) found that in previously group improved more rapidly.16 Though atropine penali­
untreated children 3 to <7 years old who were treated zation may be particularly useful in cases where there is
with optical correction alone, anisometropic amblyopia poor adherence to patching, it carries a risk of ocular side
improved by 2 or more lines in 77% of patients and effects such as light sensitivity.16 It also carries a higher
resolved in 27%, and strabismic amblyopia improved by 2 risk of reverse amblyopia, particularly in highly hyperopic
or more lines in 88% and resolved in 40%.9,11 Overall, children under 4 years old with dense strabismic
amblyopia,17 and a risk of systemic side effects.

CONTACT Eric D. Gaier eric.gaier@childrens.harvard.edu Department of Ophthalmology, Boston Children’s Hospital, Boston.
© 2021 Taylor & Francis
2 M. M. FALCONE ET AL.

EMERGING AMBLYOPIA THERAPIES which may promote neuroplasticity and could therefore pro­
mote recovery.21
In recent years, there has been an interest in new amblyopia
Li et al. studied the effect of video game play in 20 adults
treatments, particularly for children who fail or are non-
(ages 15 to 61 years) with amblyopia.23 The patients were
adherent to traditional therapies.18 There has also been
divided into three groups – action video game (n = 10, Medal
a push to develop therapies effective in older children or adults
of Honor: Pacific Assault first-person shooter game), non-
with amblyopia, particularly given growing evidence that sug­
action video game (n = 3, SimCity Societies game), and cross­
gests plasticity in the visual system beyond the period of critical
over controls who received patching therapy initially (20 hours
visual development.7 Many of these new therapeutic techni­
of total patching) followed by video game therapy (n = 7).
ques are based on the idea that binocular approaches may be
Video games were played with the non-amblyopic eye patched
superior to monocular methods for treating amblyopia
for 40–80 hours (2 hours per day). For both video game groups,
through targeting of interocular suppression and promoting
there was improvement in visual acuity in the amblyopic eye
binocularity and stereopsis.18–20 We will discuss emerging
(average 1.6 lines on a logMAR letter chart for the action game
amblyopia therapies including perceptual learning, video
group and 1.5 letter-lines for the non-action game group).
game play, and dichoptic training and review studies that
Those who were in the crossover control group showed no
have tested these approaches.
significant improvement in visual acuity after patching alone,
and in those who went on to play both action and non-action
video games for another 40 hours (n = 5), all had significant
PERCEPTUAL LEARNING
improvement in visual acuity of the amblyopic eye (average 1.7
Perceptual learning (PL) is based on the principle that perfor­ letter-lines). Despite the monocular nature of the treatment,
mance of sensory tasks can be improved with practice.7 As it stereopsis improved in all 5 patients with anisometropic
applies to the visual system, PL involves practicing challenging amblyopia who were tested, with a mean improvement of
visual tasks to promote long-lasting visual improvements21 53.6% ± 8.4%.23
through the strengthening of neural pathways engaged by the Monocular video game play has also been studied as an
same tasks. PL training can be monocular or binocular and adjunct to occlusion therapy in patients with anisometropic
requires a rigorous, supervised visual experience with amblyopia. Singh et al. randomized 68 children ages 6 to
feedback.7 During PL, the patient is asked to make fine dis­ 14 years with anisometropic amblyopia to receive either
criminations with the amblyopic eye under difficult 6 hours of occlusion therapy per day alone (n = 34) or
conditions.7 There is a wide variety of visual tasks that the 6 hours of occlusion therapy per day with 1 hour per day of
patient may be asked to perform, such as Vernier acuity, con­ video game play (n = 34).24 There was significantly greater
trast detection, letter identification, position discrimination, improvement in visual acuity in the amblyopic eye in the
spatial frequency discrimination, or motion coherence.21 Levi video game group compared to the patching-only control
et al. performed a systematic review of 14 studies where per­ group at both 1 month (mean improvement 1 line vs. 0.5
ceptual learning was used as a treatment for amblyopia.22 The lines) and 3 months (mean improvement 2.1 lines vs. 1.7
patients included in these studies ranged from 7 to 60 years, lines from baseline).24 The results suggest that monocular
and age did not account for the variance in success among video game play may be useful in conjunction with patch­
studies.22 Based on the results of these small case series, the ing, though the relative additional improvement is quite
authors concluded that PL appears to be effective for improv­ small (less than one additional line after 3 months of
ing task performance and visual acuity in amblyopia. Thus, PL treatment).
may represent an opportunity to treat adults with amblyopia,
who traditionally are thought to be treatment-resistant.
Despite this success, PL has not yet gained widespread support BINOCULAR THERAPY USING DICHOPTIC STIMULI
likely due to the small number of participants in these studies,
Dichoptic amblyopia treatments employ use of both eyes
the strict supervision requirement, and the lack of long-term
together in order to target reduction of interocular
follow-up.18 Larger randomized, control trials are needed to
suppression.19 There are three different techniques that
determine which tasks, under what conditions, and for what
utilize dichoptic presentation, where eye-selective modi­
durations PL is most effective. Additionally, many PL tasks are
fied visual stimuli are presented to achieve this goal.20 In
non-engaging and can become monotonous, which raises con­
anti-suppression therapy, the fellow, non-amblyopic eye is
cerns for difficulty with adherence.
exposed to images with significantly reduced contrast
compared to that of the amblyopic eye. Balanced binocular
viewing employs blurring of images seen by the non-
VIDEO GAME PLAY
amblyopic eye. Interactive binocular treatment presents
Video game play, particularly with commercial video games, different parts of a visual scene to each eye as the patient
might serve as a more entertaining alternative to traditional PL watches a video or plays a game that requires binocular
activities for use as a visual training tool.21 Action video games summation.20 Each of these techniques can be used alone
may have an added advantage over PL since they present or in combination. Binocular amblyopia therapy has been
a variety of visual demands and experiences.7 Playing action applied through different platforms which we will discuss
video games has also been associated with release of dopamine here (Table 1).
 SEMINARS IN OPHTHALMOLOGY 3

Table 1. Binocular amblyopia therapy using dichoptic stimuli.

Relevant
Category Platform Studies Description of activity Dichoptic technique
Video Falling blocks iPad Holmes Game where points are scored by moving Red-green anaglyphic glasses; high-contrast elements seen by the
game game et al.25 falling blocks to form complete lines of amblyopic eye and reduced-contrast by the fellow eye
Manh blocks
26
et al.
Gao et al.27
Dig rush iPad game Kelly et al.28 Action adventure game with miners digging
Holmes for gold
29
et al.
Holmes
et al.30
Video viewing Dichoptic Birch et al.19 Movies shown on a passive 3D display
movie Sauvan et al.31
Glasses with
polarized lenses;
a patterned
image mask
made of
irregularly
shaped blobs is
applied to the
images seen by
the amblyopic
eye (high
contrast) and
the inverse mask
is applied to the
images seen by
the fellow eye
(reduced
contrast)
Dichoptic movie Bossi et al.32 Movies shown on a 3D-capable computer Shutter glasses mounted in a customized ski mask; blurred image
with interactive monitor and interrupted by interactive presented to the non-amblyopic eye
tasks tasks to measure suppression
BinoVision home Mezad-Koursh Video or movie shown on custom, head- Contrast and brightness levels reduced for the non-amblyopic eye;
33
system et al. mounted goggles; customizable content superimposed moving objects and momentary repetitive bright
video frame stimuli shown only to the amblyopic eye
Luminopia One Xiao et al.34 Video shown via a smartphone on a head- Contrast levels reduced for the non-amblyopic eye; dichoptic masks
mounted display; streaming of wide variety superimposed so that parts of the video are only visible to the
of licensed content amblyopic eye
Virtual Interactive Waddingham Interactive games and movies on a 3D VR Red-green filter or shutter glasses; enriched image presented to the
reality Binocular et al.36 based computer system amblyopic eye; for games, key elements only visible to the
(VR) Treatment (I-BiT) Cleary amblyopic eye
system35 et al.37
Rajavi
et al.38
Herbison
et al.39
Diplopia game in Žiak et al.40 Games played in a 3D setting in a VR head Dichoptic setting in which the central part of the picture is shown
Oculus Rift OC mounted display connected to a computer differently to each eye; images from both eyes needed to
DK2 successfully play the games

DICHOPTIC VIDEO GAMES binocular video game therapy in amblyopia. The first study
(ATS18) compared a binocular iPad game to part-time patch­
A number of recent studies have focused on dichoptic ing in 385 children ages 5 to 12 years with amblyopia from
video game therapy in amblyopia, including several rando­ anisometropia, strabismus, or both (77% having received prior
mized, controlled trials. These studies combine dichoptic treatment).25 Participants were randomized to receive either
approaches by presenting essential game elements to each 16 weeks of the binocular falling blocks iPad game for 1 hour
eye separately with high contrast to the amblyopic eye and per day or patching of the non-amblyopic eye for 2 hours
low to the fellow eye. Thus, binocular viewing is required per day. At 16 weeks, visual acuity in the amblyopic eye
to complement the tasks in these games. Given the novelty improved from baseline by a mean of 1.1 lines in the binocular
of dichoptic therapy, initial trials have primarily targeted game group compared to 1.4 lines in the patching group. The
older children and/or patients with residual amblyopia after lack of treatment effect was at least partially attributed to low
prior treatment, possibly limiting their potential to demon­ adherence (only 22% of children in the game group played the
strate efficacy. game for ≥75% of the prescribed time), with many participants
PEDIG has published the results of 4 randomized, con­ reporting loss of interest in the game. No treatment dose–
trolled trials across two protocols (Amblyopia Treatment response relationships for visual acuity or stereoacuity were
Studies [ATS] 18 and 20) designed to assess the efficacy of appreciated.25
4 M. M. FALCONE ET AL.

An older cohort of 100 patients ages 13 to <17 years with The binocular treatment of amblyopia using video games
anisometropic, strabismic, or mixed amblyopia was treated (BRAVO) study group conducted a trial involving 115 partici­
using the same PEDIG ATS18 protocol.26 Amblyopic eye visual pants ages 7 to 55 years with monocular anisometropic, stra­
acuity improved by 3.5 letters in the binocular game group vs. bismic, or combined type amblyopia.27 Participants were
6.5 letters in the patching group. Adherence with the binocular randomized to undergo treatment with a falling blocks dichop­
video game was also poor with the older cohort; only 13% of tic video game or with a placebo video game where identical
participants completed >75% of the treatment. This arm of images were presented to both eyes for 1 hour per day for
ATS18 was stopped early due to an interim analysis showing 6 weeks. Mean visual acuity improvement in the amblyopic eye
results favoring the patching group and poor adherence to in the treatment group was 3 letters and similarly modest at 3.5
binocular therapy. Again, no treatment dose–response rela­ letters in the placebo group. A secondary analysis separating
tionships for visual acuity or stereoacuity were appreciated.26 pediatric and adult patients also showed no significant differ­
To address the problems with low adherence, a more enga­ ence in visual acuity improvement between the groups. Any
ging binocular iPad (Apple, Inc.) video game, “Dig Rush,” was potential treatment effect may have been masked by the high
tested in ATS20. Dig Rush was previously evaluated in percentage of enrolled patients included who had previously
a smaller cohort by Kelly et al.28 This pilot study compared failed traditional amblyopia therapy.27
the effectiveness of Dig Rush with patching in 28 patients ages
4 to 10 in a cross-over study. At the 2-week visit, a 1.5-line
PASSIVE BINOCULAR VIDEO VIEWING
improvement in the amblyopic eye visual acuity in the bino­
cular game group surpassed the 0.7-line improvement in the Several studies have asked whether passive dichoptic movie
patching group. Participants in the patching group who viewing might have the same effect as active video game play.
crossed over to the binocular game group caught up to the These studies have primarily consisted of pilot and small open-
binocular game group at the 4-week visit with mean improve­ label and/or single-arm studies. Birch et al. evaluated 27 chil­
ment of 1.7 lines for the binocular game group and 1.2 lines for dren with anisometropic, strabismic, or combined amblyopia
the patching crossover group. Neither group showed improve­ ages 4 to 10 years who wore polarized glasses to watch 6
ment in stereoacuity. Near perfect adherence was noted during contrast-rebalanced movies on a 3D display.19 They found
the first 2 weeks of therapy (100% for game play and 99% for improvement of 1.5 lines with treatment over a 2 week period.
patching).28 The promising results from this approach were Younger children (3–6 years) had significantly greater
carried forward into ATS20, in which Dig Rush was compared improvement than older children (7–10 years), and children
with optical therapy alone in 138 children ages 7 to 12 years, with worse amblyopic eye visual acuity at baseline had greater
96% of whom had prior treatment.29 Enrollees were required to improvement.19 In another study, the effect of binocular movie
have at least 16 weeks of optimal optical treatment or show no viewing was evaluated in 22 treatment-naïve (except for spec­
improvement in amblyopic eye visual acuity after 8 weeks of tacle correction) children ages 3 to 11 years with anisometro­
optical treatment prior to participating. Participants were ran­ pic, strabismic, or combined mechanism amblyopia.32 Subjects
domized to receive either 8 weeks of treatment with binocular were instructed to view movies for 1 hour per day while wear­
Dig Rush play for 1 hour per day for 5 days per week with ing 3D shutter glasses to control the image presented to each
spectacle wear or spectacle wear alone. Again, there was no eye for 8 to 24 weeks. The movie was interrupted every minute
difference in mean improvement in visual acuity between the by an interactive game used to measure suppression.
groups (2.3 letters for the binocular group vs 2.4 letters for the Participants exhibited significant improvement in visual acuity
spectacle group). Adherence, as measured by the device, was in the amblyopic eye (mean gain of 2.7 ± 2.2 lines). In contrast
better than in ATS18 but still low, with only 56% of those in the to other studies with binocular therapy, there was no change in
video game group completing >75% of the treatment at the suppression after treatment.32
8-week visit.29 There has been one study to evaluate the efficacy of the
Recently, data from the younger cohort from the ATS20 BinoVision home system, which utilizes binocular dichoptic
protocol were presented at the American Academy of video content by incorporating elements of different contrast
Ophthalmology annual meeting.30 Children ages 4 to 6 years and luminance levels, amblyopic eye tracking training, and
with anisometropic, strabismic, or combined amblyopia were amblyopic eye flicker stimuli in a head-mounted device.33 All
included. After 169 children underwent 4 weeks of therapy, children had either failed or did not comply with traditional
mean visual acuity improvement was greater in the binocular amblyopia treatment. Of the 27 children (ages 4–8 years)
treatment group compared to the spectacle group (1.1 vs 0.6 included in the study, 19 received dichoptic treatment and 8
lines). However, for the 164 children who completed 8 weeks of received sham treatment with an altered BinoVision device for
therapy, this difference did not remain statistically the first 4 weeks. After 4 weeks, mean visual acuity improved
significant.30 Thus, none of the 4 PEDIG studies have shown significantly in the treatment group (2.0 lines) compared to no
an advantage of binocular video game therapy over conven­ change in the sham group. After 8 weeks, mean improvement
tional therapy.25,26,29,30 Though the high rate of non- in visual acuity was 2.6 lines in the treatment group compared
adherence may have affected the results of these studies, it is to baseline. Adherence was high at 88% on average, which the
important to note that ATS18 (younger and older cohort) and authors attributed to the home video system and customizable
the ATS20 older cohort showed no dose–response relationship. video content.33
The dose–response data for the ATS20 younger cohort are not Xiao et al. conducted a pilot study of 10 children ages 4 to
yet available. 7 years using the Luminopia One therapeutic that utilizes
 SEMINARS IN OPHTHALMOLOGY 5

dichoptic video viewing via a head-mounted device.34 had resolved.37 Rajavi et al. conducted a randomized clinical
Treatment consisted of viewing video content 1 hour per day. trial to compare I-BiT games to patching with placebo games in
Nine of the 10 children had previously been treated for 38 children with unilateral amblyopia ages 3 to 10 years.38
amblyopia with either patching or atropine. The authors Visual acuity improved significantly in both groups after
claim that allowing children to choose from a wide selection 1 month of treatment (mean improvement 0.8 ± 0.9 lines in
of licensed view content that directly streamed to the head- the I-BiT group and 0.9 ± 0.9 lines in the patching with placebo
mounted device facilitated high adherence rates (mean 78%) game group), but there was no difference in the amount of
and improvement in amblyopic eye visual acuity of 2.9 lines improvement between the two groups.38
over 12 weeks of therapy.34 In a larger study, 75 amblyopic children ages 4 to 8 years
Dichoptic video therapy has also been studied as a treatment were randomized to 3 treatment groups: I-BiT game, I-BiT
for children beyond the period of critical visual development DVD, and non-I-BiT game (control where both eyes received
and adults with amblyopia. Sauvan et al. conducted a study identical stimulation).39 All three groups showed a modest yet
with 17 patients with stable, residual anisometropic or strabis­ statistically significant improvement in visual acuity at 6 weeks
mic amblyopia ages 9 to 67 years (mean 34 years).31 Ten (mean improvement 0.6 ± 0.2 lines for I-BIT game, 1.0 ± 0.2 for
participants underwent 6 sessions of 1.5 hours of dichoptic I-BIT DVD, and 0.3 ± 0.2 for control game). There was no
movie viewing and 7 underwent the same regimen but had significant difference in visual acuity improvement between
2 hours of patching over the amblyopic eye prior to each those receiving I-BiT games and those receiving non-I-BIT
session. The protocol was structured in this manner due to control games at 6 weeks, and the authors did not statistically
a shift in dominance that is known to occur after about 1 hour compare the two treated groups with the control group.
of occlusion in adults. Both groups showed improvement in Stereopsis did not improve in any of the groups. Most patients
amblyopic eye visual acuity after completing treatment (0.8 had prior treatment (67/75) and/or manifest strabismus (70/
lines in the non-patched group and 1.9 lines for the patched 75), and treatment in the study was limited to 30 minutes per
group) with no significant difference between the two groups week, which may have limited potential gains.39
immediately after treatment. However, at 1 month post treat­ A pilot study evaluated dichoptic visual training using the
ment, the patched group retained a statistically significant beta version of the computer game, “Diplopia Game” (Vivid
improvement in visual acuity compared to baseline whereas Vision, San Francisco, USA), provided via a VR head-mounted
the non-patched group did not. This study suggests that display (Oculus Rift OC DK2, Irvine, CA, USA).40 Two games
dichoptic movie viewing aided by short-term monocular were available, and both used dichoptic therapy where the
occlusion of the amblyopic eye may be helpful as a treatment central part of the picture varied in color between the two
for amblyopia in older children and adults; however, further eyes. Seventeen adults with anisometropic amblyopia (average
study is needed given the small sample size, wide age range of age 31.2 years, range 17–69 years) participated. After eight 40-
participants, and short follow-up period.31 minute sessions, there were significant improvements in mean
amblyopic eye visual acuity (mean improvement 1.5 lines) and
stereopsis (mean 263.3 ± 135.1 arcseconds baseline to 176.7 ±
VIRTUAL REALITY
152.4 after training).40
Virtual reality (VR) has become a new tool for neurorehabil­ While some of these studies offer promising preliminary
itation of many different pathologies.4142 Unlike 2-dimensional results, there is no consistent evidence yet that amblyopia
binocular therapy, VR presents content in a 3D environment in treatment with dichoptic VR is superior to conventional thera­
which the user is immersed. This therapeutic approach allows pies or non-VR-based dichoptic therapy. There are many vari­
researchers to leverage the sensory-motor adaptive capabilities ables that differ between these small pilot studies that may have
of the nervous system to manipulate sensory feedback thereby affected the results including 1) age, 2) type and amount of
providing patient-specific graduated rehabilitation.41 The time spent participating in the VR amblyopia therapy, and 3)
interactive binocular treatment (I-BiT) group was one of the number of patients who failed previous treatment. Larger ran­
first to apply this method in amblyopia treatment through their domized controlled trials are needed to ascertain the role of VR
development of a VR-based binocular system with interactive systems in managing amblyopia.
games and 3D videos with red-green filter or shutter
glasses.35,41
CONCLUSION
In a case series of 6 children with anisometropic or strabis­
mic amblyopia ages 3 to 7 years who had previously failed Much of the current research in amblyopia therapy is focused
traditional amblyopia treatment (3 treatment failures and 3 on the utility of binocular treatment in both children and
non-compliant), Waddingham et al. showed that 5 children adults. The results of the studies summarized herein are
improved visual acuity in their amblyopic eye with an average highly variable due to the diversity of interventions and
increase of 10 letters (2 lines) after a mean of 4.4 hours with the study designs. The American Academy of Ophthalmology
I-BiT system.36 Another pilot study using the I-BiT system Ophthalmic Technology Assessment Committee concluded
included 12 children with strabismic or mixed anisometropic- that, based on the more rigorously designed studies, there is
strabismic amblyopia who had not complied with or failed currently no consistent evidence to support the use of bino­
occlusion therapy. There was sustained improvement in high- cular therapy over standard treatments.42 This is largely sup­
contrast visual acuity in 58% of children, and in low-contrast ported by 4 large PEDIG randomized controlled trials
visual acuity in 67% including 2 patients in which amblyopia (protocols ATS18 and ATS20), which showed no superiority
6 M. M. FALCONE ET AL.

of binocular therapy over conventional therapy.25,26,29,30 strabismic-anisometropic amblyopia. Ophthalmology. 2012

Alternative approaches, including PL and VR treatments, Jan;119(1):150–158. doi:10.1016/j.ophtha.2011.06.043.
show promise in pilot trials, though this was also the case 12. Wallace DK. Pediatric Eye Disease Investigator Group,
Edwards AR, Cotter SA, Beck RW, Arnold RW, Astle WF,
for the treatments that eventually were shown by PEDIG to Barnhardt CN, Birch EE, Donahue SP, Everett DF, Felius J,
be ineffective. Adherence continues to be a challenge in Holmes JM, Kraker RT, Melia M, Repka MX, Sala NA, Silbert DI,
amblyopia therapy, even with these emerging therapies that Weise KK. A randomized trial to evaluate 2 hours of daily patching
would intuitively seem to circumvent the challenges of patch­ for strabismic and anisometropic amblyopia in children.
ing. Small pilot trials suggest that provision of choice and Ophthalmology. 2006 Jun;113(6):904–912. doi:10.1016/j.
ophtha.2006.01.069.
allowance for passive viewing of content may enhance 13. Repka MX, Beck RW, Holmes JM, et al. Pediatric eye disease
engagement and promote adherence. Continued research investigator group. A randomized trial of patching regimens for
with large randomized, controlled trials of these new technol­ treatment of moderate amblyopia in children. Arch Ophthalmol.
ogies are needed to further assess their efficacy and potential 2003 May;121(5):603–611. doi:10.1001/archopht.121.5.603.
superiority over traditional approaches. 14. Holmes JM, Kraker RT, Beck RW, et al. Pediatric eye disease
investigator group. A randomized trial of prescribed patching regi­
mens for treatment of severe amblyopia in children.
Ophthalmology. 2003 Nov;110(11):2075–2087. doi:10.1016/j.
Funding ophtha.2003.08.001.
15. Repka MX, Sala NA, Silbert DI, Suh DW, Tamkins SM. Pediatric
This work was supported by the NIH [K08 EY030164] and the Children's eye disease investigator group. Randomized trial of treatment of
Hospital Ophthalmology Foundation, Boston, MA. amblyopia in children aged 7 to 17 years. Arch Ophthalmol. 2005
Apr;123(4):437–447. doi:10.1001/archopht.123.4.437.
16. Pediatric Eye Disease Investigator Group. A randomized trial of
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