Amblyopia: Diagnostic and

Therapeutic Options

CAROLYN WU, MD, AND DAVID G. HUNTER, MD, PHD

● PURPOSE: To provide an overview of the current state In recent years, some long-established assumptions
of knowledge of amblyopia and highlight recent advances about the diagnosis and treatment of amblyopia have been
in diagnosis and treatment. called into question, with implications at the scientific,
● DESIGN: Review of literature and perspective. clinical, economic, and political levels. This perspective
● METHODS: MEDLINE search for amblyopia, with a provides an overview of the current state of knowledge of
review of all recent literature adding authors’ personal amblyopia and highlights recent advances in the diagnosis
perspectives on the findings. and treatment of this silent, blinding, but preventable
● RESULTS: Increased awareness of amblyopia and better condition.
screening techniques are required to identify children
who are at risk for amblyopia at a younger age. Random-
ized, controlled trials have established atropine penaliza-
tion as a viable alternative to occlusion therapy, have TYPES OF AMBLYOPIA
suggested that less treatment may be better tolerated and
AMBLYOPIA MAY RESULT FROM STRABISMUS, REFRACTIVE
as effective as more traditionally used dosages, and have
error, or deprivation. Binocularity and stereopsis are most
found no compelling evidence that treatment is beneficial
likely to be preserved when retinal blur causes amblyopia
clinically for older (over age 10) children with amblyo-
pia. and binocular alignment remains intact.
● CONCLUSION: Early detection and treatment of ambly-
● REFRACTIVE AMBLYOPIA: Isoametropic amblyopia oc-
opia can improve the chances for a successful visual
outcome. Considering that the conditions that place a curs usually in children with hyperopia greater than ⫹4.50
patient at risk for amblyopia can be identified, that diopters.11 In most highly hyperopic patients, accommo-
amblyopia responds to treatment, and that well-tolerated dation causes strabismic amblyopia, but occasionally
treatments for the condition are now recognized, it is not isoametropic amblyopia develops as the result of failure to
unreasonable to imagine that, in the near future, severe accommodate. Amblyopia is rare in patients with symmet-
amblyopia could be eliminated as a public health problem. ric myopia, because these patients simply decrease the
(Am J Ophthalmol 2006;141:175–184. © 2006 by working distance to focus the image. Meridional amblyopia
Elsevier Inc. All rights reserved.) results from uncorrected bilateral astigmatism that causes a
blurred image in a specific meridian.12,13 Astigmatism is
most likely to cause amblyopia when it is oblique.14

A
MBLYOPIA IS THE LEADING CAUSE OF VISUAL IM-
pairment in children, affecting up to 4% of the Anisometropia causes amblyopia when one eye (typi-
general population.1–9 With early detection and cally the more hyperopic eye in hypermetropes) remains
treatment, most cases of amblyopia are reversible, and the chronically blurred because of a greater accommodative
most severe forms of the condition can be prevented.9,10 need for best focus.15 Myopic anisometropia is generally
less amblyogenic than hyperopic anisometropia,16,17 except
Accepted for publication Jul 26, 2005. when unilateral high myopia occurs with myelinated nerve
From the Department of Ophthalmology, Children’s Hospital Boston, fibers.18,19 Myopic anisometropia rarely causes amblyopia
Harvard Medical School, Boston, Massachusetts.
Supported by Research to Prevent Blindness Walt and Lilly Disney until the anisometropia is ⬎2.00 diopters, although hyperopic
Amblyopia Research Award (D.G.H.). anisometropia may occur with as little as a 1.00-diopter
Conflict of Interest: D.G.H. is a co-inventor on a US Patent: “Guyton difference between the eyes.20 Astigmatic anisometropia of
DL, Hunter DG, Patel SN, et al. Eye fixation monitor and tracker. US
Patent No. 6,027,216, 22 Feb, 2000.” This patent is owned by the Johns ⬎1.50 diopters may cause amblyopia.20
Hopkins University and is not licensed by Johns Hopkins to any Ocular conditions (such as hemangiomas, chalazia, der-
commercial entity. moids, ptosis, and anterior polar cataract) may cause
Inquiries to Carolyn Wu, MD, Department of Ophthalmology, Chil-
dren’s Hospital Boston, Harvard Medical School, 300 Longwood Ave, refractive amblyopia when disturbance of corneal curva-
Boston, MA 02115; e-mail: [email protected] ture or lens structure causes astigmatism or anisometropia.

0002-9394/06/$32.00 © 2006 BY ELSEVIER INC. ALL RIGHTS RESERVED. 175

doi:10.1016/j.ajo.2005.07.060
These cases may be missed when the clinician, who is comprehensive eye examinations for school-aged children;
confident that the patient is not at risk for deprivation however, this has resulted in legally mandated examina-
amblyopia that is caused by occlusion, does not recognize tions in some states that are expensive to implement and
the refractive asymmetry. not focused on the detection of amblyopia when it is most
treatable.
● STRABISMIC AMBLYOPIA: Strabismus is the most com- Screening tests are a potentially cost-effective alterna-
mon cause of amblyopia.6,21–23 Cortical suppression from tive to comprehensive eye examinations that can be
the deviating eye is thought to be due to inhibitory performed in preverbal children.32 A variety of screening
interactions from neurons carrying nonfusable images, tests have been developed in an attempt to identify
which cause visual confusion.2,5,24 Preferential suppression patients who are at risk for amblyopia. The major ap-
of one eye may result in amblyopia and loss of binocular proaches currently in use include office-based acuity test-
function and stereopsis despite focused retinal images in ing and screening devices, which include photoscreeners
both eyes.2,5,6 and autorefractors.
Photoscreening devices use retinal reflections to deter-
● DEPRIVATION AMBLYOPIA: Deprivation amblyopia re- mine refractive error and media opacities and to provide a
sults from occlusion of the pupil and lack of pattern rough estimate of binocular alignment. Photograph-based
stimulation. This may be seen in media opacities, ptosis, or screeners include the iScreen (iScreen LLC, Memphis,
excessive patching therapy for amblyopia treatment (oc- Tennessee, USA)33 and the MTI Photoscreener (Medical
clusion amblyopia or reverse amblyopia). Deprivation Technology, Inc, Rivera Beach, Florida, USA).34 The
amblyopia is the least common type of amblyopia, ac- Power Refractor (PlusoptiX, Nürnberg, Germany) is a
counting for ⬍3% of cases,25 but it has the most potential video-based device that also tracks the corneal light
to cause severe amblyopia. reflexes to estimate binocular alignment.35
Hand-held autorefractors such as the Retinomax (Right
Manufacturing Co, LTD, Tokyo, Japan) and SureSight
SCREENING FOR AMBLYOPIA (Welch Allyn, Skaneateles Falls, New York, USA) mea-
sure refractive error monocularly as the primary indicator
AMBLYOPIA IS REMARKABLY RESPONSIVE TO TREATMENT of possible amblyopia risk.36 Although these instruments
if therapy is initiated early in life; however, delayed cannot measure misalignment, they identify patients with
treatment can result in severe visual impairment.26,27 refractive error that may cause accommodative esotropia or
Many of the common conditions that can lead to ambly- sensory strabismus. Although any angle of strabismus may
opia can be difficult to detect in children, with half of all lead to amblyopia, it remains unclear what magnitude of
amblyopia cases undetected until age 5 years.28 The Amer- refractive error is most likely to place a patient at risk for
ican Academy of Pediatrics29 states that vision screening strabismus; this threshold varies among patients.
should begin at birth and continue as part of a child’s The Vision in Preschoolers (VIP) Study32 was a direct
regular medical checkups. All newborn infants should be comparison of 11 preschool vision screening tests. Three
screened in the nursery with the use of a red reflex test to levels of risk were established: Group 1 “very important to
check for media opacities; in addition, newborn infants detect and treat early”, Group 2 “important to detect
with a family history of congenital cataracts, retinoblas- early”, and Group 3 “detection clinically useful”. A subject
toma, and genetic or metabolic diseases should be referred was placed in a particular risk category on the basis of
for a dilated fundus examination. Infants should be eval- agreed-upon thresholds for hyperopia, astigmatism, aniso-
uated for fixation preference, ocular alignment, and eye metropia, strabismus, and visual acuity.
diseases by 6 months of age and at each routine visit. The VIP study found that testing visual acuity was no
Formal visual acuity testing and stereopsis evaluation better than the best automated screening tests at detecting
should be attempted beginning at 3 years of age. However, the targeted conditions.32 Visual acuity tests took longer to
it is not clear that primary care providers are given administer than the automated tests. The Retinomax
sufficient training or resources to perform these tasks autorefractor was one of the most effective devices, with a
effectively. sensitivity of 64% when specificity was set at 90%. With
With 19 million preschool children in the United stratification by risk severity, the sensitivity of the Retino-
States,30 nearly 800,000 are at risk for amblyopia, and max was 88% for Group 1 patients, 55% for Group 2
400,000 may not be identified before school age. These patients, and 37% for Group 3 patients. The SureSight
children will experience preventable vision loss because of showed similar levels of sensitivity and specificity. Addi-
lack of detection.31 Controversy exists regarding the best tional studies that are using less skilled personnel to
method to identify these children. A screening program perform the tests are underway currently.
targeted at children well before school age is necessary to The results of the VIP study suggest that none of the
detect those who are at risk for amblyopia during the time tested devices or protocols are adequate for cost-effective
that treatment will be most effective.9,10 Some advocate screening of entire populations for amblyopia risk. If all 20

176 AMERICAN JOURNAL OF OPHTHALMOLOGY JANUARY 2006

million preschool children in the United States were increased by the unnecessary prescription of glasses to
screened with a test with 90% specificity and sensitivity to patients who lack amblyogenic factors.40
detect 1 million patients with amblyopia (5% prevalence), Mandates to perform screening, rather than comprehen-
2 million unaffected children would be referred for unnec- sive eye examination, will be less costly to implement and
essary eye examinations, and 100,000 patients with ambly- likely to reach more children who are at risk because they
opia would be missed. Assuming a cost/screening of $20 encourage the test to be brought to the patient (at the
and a cost of a comprehensive eye examination of $100, school or primary care setting) rather than requiring the
the program would cost $400 million for screening plus patient to seek the test at a specialist’s office. This
$200 million for unneeded eye examinations to detect requirement for travel adds an important barrier to care
900,000 cases or a total of $667 per detected case. that paradoxically may limit access, even if the actual
(Mandated comprehensive eye examinations for all chil- examination is performed at no charge to the patient.
dren would cost $2 billion to detect all 1 million cases or A less-widely recognized problem with amblyopia
$2000 per detected case.) To reduce the cost of screening, screening is access to care for patients in whom risk
a low-cost screening protocol with extraordinarily high factors have been identified. In one study, only 30% of
specificity that can be used to screen preliterate children parents who were notified of the presence of amblyopia
must be developed. followed up with treatment recommendations.41 Thus,
although it is clear that amblyopia is a major public
● VISION SCREENING WITH VISUAL EVOKED POTEN- health problem that could be solved by timely and
TIALS: Since the publication of the first VIP study, a new effective screening and therapy, there is no approach at
technologic approach to preschool screening has been present that can accomplish this goal. The best strategy,
described that uses a visual evoked potential (VEP) device, given the present limitations of screening, is (1) to
the ENFANT II system (Diopsys Corporation, Metuchen, improve awareness of both primary care providers and
New Jersey, USA).37 This device uses a sweep stimulus and the public that this is a silent, blinding condition that is
treatable if detected (for example, the Illinois Pediatric
analyzes the VEP differences between fellow eyes. In one
Vision and Amblyopia Awareness Campaign, the first
study that involved 122 patients aged 6 months to 5 years,
state-sponsored campaign in the United States to target
the test was completed by 94% of patients and required an
amblyopia specifically42 and the Massachusetts state law
average of 10 minutes to complete. The device yielded a
that mandates screening, rather than eye examinations,
sensitivity of 97.3% and specificity of 80.8%. This level of
for amblyopia detection), (2) to determine whether a
specificity may not be adequate for large-scale screening,
combination of the best available tests might improve
but further investigations must be performed to better
the sensitivity and specificity of screening, (3) to con-
characterize this approach. The 10-minute testing time is
tinue to improve pediatric vision screening technol-
equivalent to the time for standard visual acuity testing but
ogy,43 (4) to compensate providers who perform
longer than the testing time for most automated tests. The pediatric vision screening (perhaps including direct
proposed strategy of billing insurance for a VEP test compensation of orthoptists in the United States), and
rather than for a vision screening test may result in this (5) to improve and promote access to care for children
approach becoming prohibitively expensive for wide- who are discovered to be at risk for amblyopia.
spread application.

● VISION SCREENING WITH MANDATORY COMPREHEN-

SIVE EYE EXAMINATIONS: Mandatory eye examinations
TREATMENT OF AMBLYOPIA
of all children that are performed by optometrists or THE FIRST STEP IN AMBLYOPIA TREATMENT IS TO PROVIDE
ophthalmologists before a child enters school have been a clear retinal image for the amblyopic eye if deprivation
proposed as an alternative to vision screening to detect exists; however, merely removing the initial deprivation
amblyopia.38 Although comprehensive screening at age 4 condition is usually insufficient to reverse the amblyopia.
years, as administered in the Scandinavian model that used The second step consists of occluding or penalizing the
an incremental combination of nonophthalmic personnel, dominant eye.
orthoptists, and ophthalmologists9,10 may be effective, Occlusion therapy with patching of the dominant eye
there is no evidence that screening at age 5 to 6 years is has been the cornerstone of amblyopia treatment, despite
sufficiently timely to be effective, and the use of profes- the lack of data that demonstrate its superiority over other
sionals to perform the testing adds to the expense. This law options.44 Practitioners disagree on how much patching
and efforts to provide free comprehensive eye examina- should be prescribed. The success of patching seems to
tions for infants may have the negative consequence of correlate with the actual number of hours that the eye is
discouraging primary care providers from performing pedi- patched45; however, compliance rates vary widely22,45– 47
atric vision screening.39 There is evidence that the expense because of physical, visual, social, and psychologic issues
to society of mandated eye examinations will be further that are associated with patching.44

VOL. 141, NO. 1 AMBLYOPIA 177

 TABLE. Summary of PEDIG Amblyopia Studies

Treatment Amblyopia Severity Follow-up

Study No. Enrolled Age (y) (Atropine or Patching) (Moderate or Severe) (mo)

Atropine vs patching for moderate amblyopia44,56,57 419 3–6 A&P M 24

2 hours vs 6 hours daily patching for moderate amblyopia58 189 3–6 P M* 4
6 hours vs full-time daily patching for severe amblyopia60 175 3–6 P S 4
Daily vs weekend atropine for moderate amblyopia63 168 3–6 A M 4
Treatment of amblyopia in children 7 to 17 years52,70 507 7–17 A&P M, S 6
Recurrence of amblyopia after cessation of treatment73 156 3–7 A&P M, S 12

A ⫽ Atropine penalization; M ⫽ moderate amblyopia (20/40 –20/80); P ⫽ occlusion (patching); S ⫽ severe amblyopia (20/100 –20/400).
*Moderate amblyopia (20/40 –20/100).

Atropine penalization is an alternative to patching for ● ATROPINE VS PATCHING FOR THE TREATMENT OF
amblyopia therapy.48,49 Atropine prevents the treated eye MODERATE AMBLYOPIA: The first PEDIG amblyopia tri-
from accommodating, thus blurring the vision at near and al44 compared atropine (1 drop daily) with patching (ⱖ6
allowing the amblyopic eye to be used preferentially. In hours daily) for the treatment of moderate amblyopia.
patients who are hyperopic, the blurring effect of atropine Improvement was faster in the patching group. At six
can be augmented by prescribing less than the full hyper- months, visual acuity in the amblyopic eyes had im-
opic correction, which effectively blurs the vision at both proved by approximately three lines, with successful
distance and near; however, this may increase the risk of treatment in 75% of both groups. The treatment effect
secondary amblyopia in the sound eye.50 Atropine gener- did not vary with type of amblyopia, age, or initial visual
ally has been advocated for amblyopia with vision better acuity.56
than 20/100, because dioptric blur of the sound eye may At the 2-year follow-up examination, one in three
not be sufficient to switch fixation in severe amblyopia.48,51 patients was still being treated for amblyopia.57 The visual
In some cases, occlusion and atropine penalization may be acuity in the amblyopic eye improved similarly in both
combined.52 groups, approximately three to four lines, with treatment
In 1997, the Pediatric Eye Disease Investigator Group success in ⬎80% of subjects. Final visual acuity was 20/32
(PEDIG) was formed to conduct research on eye disorders in both groups (approximately two lines worse than the
that affect children.53,54 A major focus of PEDIG has been visual acuity of the sound eye). PEDIG plans to re-
the evaluation of different treatments for amblyopia (the examine the children in this study at ages 10 and 15
Amblyopia Treatment Studies [ATS]).55 The table gives a years to determine the long-term visual acuity and
summary of the PEDIG amblyopia studies that have been stereopsis outcomes.
performed to date.
The multicenter design of the PEDIG studies allowed ● TWO VS SIX HOURS DAILY PATCHING FOR MODERATE
rapid recruitment of hundreds of subjects to achieve AMBLYOPIA: To address the question of how many hours
statistically powerful studies. All studies used similar meth- to patch, PEDIG compared 2 vs 6 hours of daily patching
ods and analysis: Visual acuity was measured in a standard- for the treatment of moderate amblyopia.58 Surprisingly,
ized fashion with the HOTV test (presenting single letters the extra patching did not appear to give added benefit: At
with crowding bars) in young patients, or the Early the 4-month follow-up examination, the visual acuity
Treatment of Diabetic Retinopathy Study (ETDRS) chart in the amblyopic eyes in both groups had improved by 2.4
in older patients. Amblyopia was defined as moderate if lines, with treatment deemed successful in 62%.
acuity was 20/40 to 20/80 (or 20/100) (Table) and severe
if acuity was 20/100 to 20/400. Children 3 to ⬍7 years of ● SIX HOURS VS FULL-TIME DAILY PATCHING FOR
age were included, except in one study of older children. SEVERE AMBLYOPIA: This ATS protocol compared 6
Patients were required to perform near visual activities for hours vs full time (all but 0 to 1 waking hours) patching for
1 hour each day while patching. Treatments were contin- severe amblyopia.59,60 Once again, the surprising finding
ued until the amblyopic eye met the criteria for successful was that the extra prescribed patching appeared to give no
treatment or until a predetermined time period (usually 4 additional benefit. At the 4-month follow-up examination,
or 6 months) elapsed. Treatment of moderate amblyopia visual acuity in the amblyopic eye in both groups had
was successful if acuity improved to ⱖ20/30 and/or ⱖ3 improved by 4.7 to 4.8 lines, with visual acuity improving
lines. 3 lines or more for 82% to 86% of patients.

178 AMERICAN JOURNAL OF OPHTHALMOLOGY JANUARY 2006

● DAILY VS WEEKEND ATROPINE FOR MODERATE AM- ● RISK OF AMBLYOPIA RECURRENCE AFTER CESSATION
BLYOPIA: How frequently must atropine be administered OF TREATMENT: In a nonrandomized study, PEDIG
to effectively treat amblyopia? Arnold and associates61 found that amblyopia recurred (defined as a ⱖ2 logMAR
found that the penalization effect of atropine was present decrease in visual acuity after therapy) in 24% of children
for less than 48 hours; Simons and associates62 reported by 1 year after treatment stopped, with recurrence usually
that intermittent atropine therapy (1 or 2 days a week) was detectable within 13 weeks of discontinuation.73 The most
as effective as daily atropine. PEDIG compared daily vs important finding was in children who were treated with
weekend atropine for the treatment of moderate amblyo- moderately intense patching (6 to 8 hours/d) had a
pia.63 Once again, there was no difference between groups. recurrence rate of only 14% when treatment was first
At the 4-month follow-up examination, visual acuity in reduced to 2 hours/d, compared with a 42% recurrence rate
both groups had improved by 2.3 lines, with equivalent when treatment was discontinued abruptly. The authors
success rates. suggested that amblyopia therapy should be tapered before
it is discontinued but cautioned that a randomized, con-
● TREATMENT OF AMBLYOPIA IN CHILDREN 7 TO 17 trolled trial has not been done.
YEARS OLD: The American Academy of Ophthalmology
● LIMITATIONS OF PEDIG STUDIES: In the PEDIG stud-
Preferred Practice Pattern for amblyopia recommends that
children should be considered for treatment up to age ies, findings were based on prescribed treatment and not
10 years,64 but experts differ on this topic.6,26,65– 67 Numer- actual treatment, with only self-reported compliance mea-
ous anecdotal reports and case series suggest that visual sures. Parents admitted worse compliance with more pre-
acuity may improve in older children (and even adults) scribed hours of patching. Thus, the difference between
with treatment.22,46,65,68 –72 the 2- vs 6-hour group in the treatment of moderate
To address this controversy, PEDIG conducted a study amblyopia and the 6-hour vs full-time group in the
of amblyopia therapy in ⬎500 amblyopic children aged 7 treatment of severe amblyopia was probably less than
to 17 years.52 Patients were provided with optimal optical might be prescribed. Although compliance is essentially
unknown in these studies, in the clinic treatments are
correction and randomized to either the treatment group
prescribed but not monitored. Thus, for a study of clinical
(2 to 6 hours of prescribed daily patching) or the optical
efficacy, it is not unreasonable to measure the outcome in
correction group (spectacle correction only). Patching was
terms of prescribed (not actual) treatment. Clinically we
supplemented with daily atropine in the 7- to 12-year-old
can accept that it does not matter whether we prescribe 2
group only. The criteria for improvement were less strict
vs 6 hours of patching for amblyopia, as long as we
than in the previous PEDIG studies. A responder was
recognize that scientifically the total number of hours of
defined as a patient whose vision in the amblyopic eye
occlusion may not have been sufficiently different to assess
improved ⱖ10 letters (two lines) by 24 weeks.
the true dose-response relationship of patching.
Surprisingly, 24% of patients in the optical correction In the various studies, visual outcome measures were
group (intended as a control group) responded to treat- taken after only 4 to 6 months of treatment. Although this
ment. In the 7- to 12-year-old group, 53% of the treatment was chosen for practical purposes and concerns for patient
group were responders, but in the 13- to 17-year-old group, care, longer follow-up is necessary to determine whether
only 25% of the treatment group were responders. Patients more differences emerge between treatment groups.
in this older age group responded best if they had not been The PEDIG studies prescribed 1 hour of near visual
treated previously for amblyopia, with a 47% response rate activities in conjunction with patching treatment. There is
in the treatment group. considerable debate as to whether this can augment
Thus, in older patients, visual acuity improved only therapy. There was no attempt to determine whether near
slightly with treatment, failing to return to within two activities made a difference in the PEDIG studies. The
lines of normal in most patients. It remains to be seen PEDIG investigators have thus created a new question and
whether the small measured improvement in visual acuity a new study. Clinicians who adjust their practice to
will be lasting and/or of any functional significance for the incorporate the PEDIG study occlusion results must con-
patients. The study raises the question of whether patients sider whether to include near activities to match the
of any age, even middle age, with amblyopia are able to PEDIG protocol.
respond slightly to patching. If a patient can show a
10-letter response to treatment at any age after 13 years ● EMOTIONAL IMPACT OF AMBLYOPIA TREATMENT:
and that 10-letter response is clinically only important in Once the diagnosis of amblyopia is made, the disease is
the setting of a catastrophic loss of vision in the sound eye, likely to cause adverse emotional impact and distress on
there would be no advantage to the initiation of treatment. the child and the family, either because of treatment74 or
It is premature to recommend screening for amblyopia in lack of treatment.75 PEDIG assessed the quality of life and
older children until the benefits of therapy and longevity of psychosocial impact of amblyopia treatment on the family.76
response at this age are better understood. Parents completed an Amblyopia Treatment Index (ATI)

VOL. 141, NO. 1 AMBLYOPIA 179

questionnaire after 5 weeks of treatment. Both treatment Does atropine penalization give better stereopsis out-
regimens were well tolerated by the child and family. comes than patching, considering that it allows for the
However, atropine was accepted significantly better than stimulation of binocular function during treatment?48,62,87
patching in terms of adverse effects, difficulty with com- There is no evidence of a difference in monocular or
pliance, and social stigma. The ATI scores were not binocular visual function outcome between children who
influenced by patient age, cause of amblyopia, or depth of are treated with penalization or occlusion.62 PEDIG re-
amblyopia. cently found no difference in stereopsis or suppression
Other studies have found that amblyopia treatment is between children treated with patching vs atropine for
well tolerated.27,77 Although treatment may cause some moderate amblyopia and followed for 2 years.57 In fact, in
distress, this distress is usually mild and does not cause a the subset of children with anisometropic amblyopia,
permanent negative impact on a child’s global well-being stereopsis and fusion were better at 2 years in the patching
or behavior.27,77 Given the lifelong disabilities that may be group than in the atropine group. This difference was not
associated with amblyopia, including an increased risk of seen in children with strabismic or combination strabismic
serious visual loss in the fellow eye,78 the temporary distress and anisometropic amblyopia. Thus, there is no convinc-
that may be associated with treatment is generally worth ing evidence that the choice of amblyopia therapy will
the effort; however, the potential benefits of treatment influence the binocular outcome.
must be reassessed continually to avoid prolonging such
therapy unnecessarily. ● USE OF REFRACTIVE SURGERY IN ANISOMETROPIC
AMBLYOPIA: Children with anisometropia are treated
● OCCLUSION DOSE MONITORS: The success of amblyo- conventionally with spectacles and/or contact lenses.
pia treatment must depend on compliance with occlusion However, spectacle correction may lead to aniseikonia,
therapy,45,47 yet few studies have ever measured compli- and children may become contact lens intolerant, which
ance objectively. An electronic occlusion dose monitor leads some ophthalmologists to suggest refractive surgery in
(ODM) has been developed to measure compliance with these cases.
patching.45,79 The device works by detecting a temperature Several reports have suggested that refractive surgery
difference between the front and back of a patch when the may be beneficial compared with traditional intervention
patch is worn. The ODM, although still too complex to for amblyopia therapy. By reducing anisometropia, refrac-
implement for routine clinical use, seems to assess compli- tive surgery has been reported to improve spectacle toler-
ance reliably for research purposes.80,81 ance, facilitate amblyopia therapy, and enhance binocular
In the prospective Monitored Occlusion Treatment of vision.93 Treatment with refractive surgery, which includes
Amblyopia Study (MOTAS),82,83 72 children aged 3 to 8 photorefractive keratectomy, laser in situ keratomileusis,
years with strabismic and/or anisometropic amblyopia were and laser-assisted subepithelial keratectomy, has yielded no
prescribed 6 hours of occlusion dose–monitored daily more complications in the pediatric population than would
patching. Mean visual acuity improved from 0.50 ⫾ 0.36 be expected in adults.93–99
to 0.15 ⫾ 0.25 logMAR. Average compliance was 48% of Autrata and Rehurek93 found that visual acuity and
prescribed hours (2.8 hours). Increasing dosage beyond 2 binocular vision outcomes were better in children who
hours a day did not affect the final visual outcome; received permanent surgical correction of their anisome-
however, those patients with a higher dosage achieved a tropia than in children who were treated conventionally
successful outcome more quickly. There was an approxi- with contact lenses while undergoing amblyopia treat-
mate dose-response rate of 0.1 log unit (one line) improve- ment. Refractive surgery also has been used to treat
ment for every 120 hours of occlusion. More than 80% of children who have completed amblyopia therapy but
the visual acuity improvement occurred during the first 6 cannot comply with spectacle or contact lens use, with
weeks of treatment. Treatment outcome was significantly some reports of improved visual acuity or binocular vision
better for younger (⬍4 years of age) than older (⬎6 years in these patients.94,96,99 The reports of improved vision in
of age) children. Thus, the MOTAS and the PEDIG amblyopic eyes may be related in part to optical phenom-
studies are essentially in agreement, suggesting that 2 hours ena; specifically, by moving the refractive correction from
of occlusion may be adequate for treatment of moderate the spectacle plane to the corneal plane, there is less
amblyopia, but the MOTAS was able to determine a minification of the image.
dose-response relationship of occlusion therapy. Because of the level of cooperation required for refrac-
tive surgery, patients who could benefit most from the
● IMPROVEMENT OF STEREOPSIS: Stereopsis is known to therapy (children ⬍4 years old who will not wear glasses or
decrease with reduced visual acuity20,84 – 86 and to improve contact lenses) are least likely to be treatable. Thus,
when refractive error is corrected.87,88 Several studies have although a few studies have suggested that refractive
suggested that when stereopsis is present, the risk of surgery may be beneficial in some cases of anisometropic
moderate-to-severe amblyopia is reduced in patients with amblyopia, studies of more treated patients followed for
esotropia and/or anisometropia.89 –92 longer time periods should be completed before refractive

180 AMERICAN JOURNAL OF OPHTHALMOLOGY JANUARY 2006

surgery is considered for routine treatment of anisome- may be better tolerated and as effective as, but again
tropic amblyopia. possibly less rapid than, more traditional dosages. For older
children (⬎13 to 17 years old) who have never been
● LEVODOPA/CARBIDOPA: Levodopa/carbidopa, which is treated, one study showed a slight gain in visual acuity
used to treat Parkinson’s disease, has been studied as with treatment, but it is not known whether this gain is
supplemental treatment to occlusion therapy for amblyo- lasting, whether it could be attained even later in life, or
pia.100 –107 The overall improvements in visual acuity have whether it provides any benefit such as improved binocular
been small and not clinically better than with occlusion vision.
alone. There are concerns regarding regression and long- In light of recent advances in our understanding of the
term stability of vision after the cessation of treat- response of amblyopia to treatment, the following guide-
ment.100,101,104 –106 At this time, there is no clear benefit to lines for care may be suggested. For new onset moderate
routine clinical use of these agents in amblyopia therapy.
amblyopia, it is reasonable to offer either atropine penal-
ization or occlusion therapy. Penalization may be offered
● UTILITY VALUE OF AMBLYOPIA TREATMENT: Mem-
daily or on weekends, with the understanding that it takes
breno and associates108 have presented a detailed cost-
longer to achieve the same acuity outcome as with patch-
utility analysis of amblyopia therapy. Although the cost
ing. Occlusion for mild amblyopia may be offered for as
analysis of amblyopia treatment is relatively straightfor-
ward, analyses of cost-utility can become encumbered by little as 2 hours each day, but this may also increase the
difficulty determining the impact of amblyopia on the time it takes to achieve best acuity. Because the definitive
quality of life.109 In the study of Membreno and associates, study of 2 hours of patching used 1 hour of near work each
they found a range of dollars expended per quality-adjusted day as part of the protocol, this should be prescribed if 2
life year ($/QALY) from $2053 to $2509. Interventions hours of patching are prescribed until more is known about
with ($/QALY) of ⬍$20,000 are considered especially the role of near tasks in amblyopia therapy. Patients with
cost-effective. Two studies from Europe have suggested severe amblyopia may be treated effectively with 6 hours of
that the ($/QALY) may be higher, both for the treatment occlusion. In some cases, it may be helpful to combine
of amblyopia110 and for vision screening.111 atropine and occlusion or to remove the hyperopic spec-
tacle lens from the sound eye, but this carries with it a
greater risk of iatrogenic amblyopia in the sound eye. For
DISCUSSION patients ⬎12 years old, there is not yet convincing
evidence that treatment is beneficial; however, if a child
AMBLYOPIA IS THE MOST COMMON TREATABLE CAUSE OF has never had treatment, it is reasonable to offer treatment
decreased vision in children and remains as one of the to the patient and family. Refractive surgery for anisome-
most common causes of decreased vision in adults. Aside tropia, occlusion dose monitoring, and levodopa/carbidopa
from the visual deficits, amblyopia may also have a nega- systemic therapy are not ready for routine clinical appli-
tive psychosocial impact. Patients with an amblyopic eye cation and should remain in the purview of amblyopia
have an increased risk for vision loss in the fellow eye and investigators.
considerably greater disability when this does occur. As a Considering that the conditions that place a patient at
result, cost-utility analysis indicates that amblyopia ther- risk for amblyopia can be identified by appropriately
apy is highly cost-effective when compared with other trained personnel, that amblyopia responds to treatment,
health care interventions.108
and that well-tolerated treatments for the condition are
The prognosis for any patient with amblyopia is depen-
now available, it is not unreasonable to imagine that, in
dent on the type and depth of amblyopia, the age at
the near future, severe amblyopia could be eliminated as a
diagnosis, and compliance with treatment. Early detection
public health problem. This goal, although attainable, will
and treatment of amblyopia can improve the chances for a
successful visual outcome. Increased awareness of amblyo- require improvements in public awareness, better screen-
pia and better screening techniques are needed to identify ing protocols at the level of the primary care provider, and
children who are at risk for amblyopia at a younger age. full access to medical care for at-risk patients.
Any screening program must include a robust follow-up
mechanism to assure that patients are evaluated and
treated appropriately once they are identified by a failed
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 Biosketch
Carolyn Wu, MD, received a BA from the University of Pennsylvania and a MD from Albert Einstein College of
Medicine. Her residency was at the New York University School of Medicine and Manhattan Eye, Ear, and Throat
Hospital. She completed a fellowship in pediatric ophthalmology at Children’s Hospital Boston, where she joined the
faculty and is an Instructor in Ophthalmology at Harvard Medical School.

VOL. 141, NO. 1 AMBLYOPIA 184.e1

 Biosketch
David G. Hunter, MD, PhD, is Ophthalmologist-in-Chief, Children’s Hospital Boston/Associate Professor of Ophthal-
mology, Harvard Medical School. He has a BS in electrical engineer from Rice University and a PhD (cell biology) and
MD from Baylor College of Medicine. His residency was at the Massachusetts Eye and Ear Infirmary and he was a fellow
in pediatric ophthalmology at Johns Hopkins’ Wilmer Eye Institute. After 10 years on faculty at Wilmer, he relocated to
Boston in 2002.

184.e2 AMERICAN JOURNAL OF OPHTHALMOLOGY JANUARY 2006