Pediatr Clin N Am 50 (2003) 189 196

Amblyopia
David Mittelman, MDa,b,c,*
a

Department of Ophthalmology, University of Illinois at Chicago, UIC Eye Center,

1855 W. Taylor, Chicago, IL, USA
b
Department of Pediatric Ophthalmology, Lutheran General Childrens Hospital,
1775 W. Dempster, Park Ridge, IL, USA
c
Pediatric Ophthalmology, Adult Strabismus Center, Ltd., 1875 West Dempster Street, Suite 610,
Park Ridge, IL 60068, USA

The term amblyopia refers to an abnormality of visual development characterized by decreased visual acuity, not correctable by glasses or other optical
means, which is generally unilateral but may occasionally be bilateral, for which
no obvious pathologic basis can be detected by the physical examination of the
eye or visual pathway. Amblyopia is associated with form deprivation and/or
abnormal visual interaction and is usually reversible if treatment is instituted in a
timely manner [1].
The word amblyopia comes from the Greek and literally means dull sight.
The diagnosis of amblyopia is made when a complete ophthalmologic examination reveals reduced visual acuity that is not explained by any obvious organic
lesion of the eye or optic nerve. Amblyopia should be considered if strabismus is
present, if there is a large refractive error, especially in one eye, or if organic
pathology is present in an infant or young child. Over a century ago, von Graefe
formulated the classic description of amblyopia: it is the condition in which the
observer sees nothing and the patient sees very little [2].
Amblyopia is common; it affects approximately 2% to 2.5% of the general
population or nearly 6 million Americans. This disorder is responsible for loss of
vision in more people under 45 years of age than all other forms of eye disease or
trauma combined. Indeed, one large study by the National Eye Institute showed
that amblyopia remains the number one cause of monocular vision loss in people
ages 70 years or younger [1,3].

* Pediatric Ophthalmology, Adult Strabismus Center, Ltd., 1875 West Dempster Street, Suite 610,
Park Ridge, IL 60068.
E-mail address: mittelmd@yahoo.com
0031-3955/03/$ see front matter D 2003, Elsevier Science (USA). All rights reserved.
PII: S 0 0 3 1 - 3 9 5 5 ( 0 2 ) 0 0 1 0 7 - 4

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Clinical findings
The most important clinical feature of amblyopia is reduced vision. The extent
of this visual loss varies greatly. The loss may be as little as one or two lines
difference in Snellen acuity, or vision may be reduced to the level of legal
blindness or worse. This decrease in visual acuity is of greater magnitude when
the patient is asked to read a complete line on the eye chart rather than individual
letters or symbols. This finding has been termed the crowding phenomenon.
Testing done with single optotypes may fail to disclose the full extent of vision
loss in amblyopic individuals and may indeed mask the presence of significant
amblyopia. Therefore, when the clinician measures visual acuity, it is important
always to present children with full lines of letters or symbols to avoid
overlooking some cases of amblyopia.
In addition, vision loss from amblyopia can be differentiated from vision
loss secondary to organic reasons by the patients response to neutral density
(ie, dark) filters. The amblyopic eye is much more resistant to further
degradation of vision when dense filters are placed before the eye, so that
vision does not decrease in very dim light, as it does in nonamblyopic eyes.
The amblyopic eye seems to behave in a manner similar to the dark-adapted
normal eye [1].
The diagnosis of amblyopia in preverbal infants and children requires special
examination techniques, because they are unable to respond to standardized eye
charts. Although complex techniques to measure visual acuity in infants such as
forced preferential looking or visual evoked responses are of value in the
research setting, they are not readily available to most clinicians. Therefore, in
the clinical setting, fixation pattern is the most commonly used parameter to
diagnose amblyopia in nonverbal children. A penlight or other interesting
object is presented before the child. If strabismus is present, the examiner then
occludes the fixating eye and observes the childs ability to fixate and follow
with the deviating eye. When no amblyopia exists, the childs deviating eye
quickly moves centrally to take up fixation and maintains that position for quite
a while, even after the occluder is removed from the fellow eye. If the patient is
unable to fixate centrally or maintains that fixation only briefly when the
dominant eye is re-exposed, amblyopia can be presumed to exist. Fixation
pattern is more difficult to evaluate when little or no strabismic deviation is
present. In that case, a prism is placed before one eye, simulating a strabismus,
allowing the experienced clinician to estimate fixation ability.
Forced preferential looking tests [4] utilize infants innate tendency to gaze at
sharply contrasting objects rather than at blank surfaces. A hidden observer
watches as two paddles designed with either black and white stripes or a blank
gray field are presented before the infant. The observer records which of the two
paddles the baby prefers to look at. As the stripes become finer, the difference in
the appearance of the paddles diminishes, until eventually the subject can no
longer differentiate between the two. Visual acuity can be extrapolated from the
size of the stripes producing a fixation preference.

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Visual evoked potentials may also be used to determine infant visual acuity. A
series of checkerboard or striped patterns is presented before the child while scalp
electrodes record the pattern of cortical responses elicited from the brain. Again,
the minimum magnitude of the target producing a distinct electrical response in
the brain indicates threshold visual acuity.

Classification
There are three major types of amblyopia: strabismic amblyopia, anisometropic amblyopia, and deprivation amblyopia [1]. Patients with strabismus who
strongly favor fixation with one eye, rather than alternating fixation between both
eyes, are at risk for developing amblyopia. Strabismic amblyopia results from
abnormal binocular interaction that develops from misalignment of the optical
axes. When the eyes are not parallel, images fall on disparate parts of the retina,
resulting in double vision or optical confusion. To avoid this uncomfortable
situation, the patient unconsciously suppresses the image from the nonpreferred
eye. In a young child, this chronic suppression of the visual stimulus from one
eye leads to loss of vision (amblyopia). Amblyopia is much more likely to occur
in esotropia than from any other form of strabismus.
Anisometropia refers to a difference in refractive error between the two eyes.
If this refractive error is not properly corrected, one of the retinal images will be
out of focus compared with the other. The clearer image will then be favored,
resulting in vision loss from amblyopia in the fellow eye. This form of
amblyopia is particularly difficult to diagnose in the preverbal child, because
there may be no associated strabismus or other external manifestation to alert the
pediatrician. Anisometropic amblyopia is usually diagnosed following a routine
screening examination either in the primary care physicians office or in the
school setting.
Finally, deprivation amblyopia results when the eyes fail to receive clearly
formed images on the retina. Opacities of the optical system such as cataract or
corneal opacity are often precipitating factors. Deprivation amblyopia can be
quite profound in the newborn period. For example, if visually significant
congenital cataracts or other media opacities are not removed in the first few
months of life, visual loss from amblyopia is usually irreversible [5].
A special form of deprivation amblyopia is termed occlusion amblyopia. This
type of amblyopia results most commonly from the iatrogenic occlusion of one
eye to treat amblyopia in the fellow eye. As a result of treatment, the eye being
patched, that is, the sound eye, becomes amblyopic as the previously amblyopic
eye improves in vision. This problem can often be avoided by frequent
monitoring of the vision in each eye during amblyopia therapy. Very young
infants may have to be seen as often as weekly to guard against the development
of this condition. Occlusion amblyopia can also occur any time the pupillary axis
is obstructed, such as after a black eye, acquired ptosis, and so forth. Likewise,
the primary care doctor should be aware that the seemingly harmless practice of

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patching an infant or toddler for a corneal abrasion or other eye injury can result
in amblyopia and therefore should be undertaken with care.
A fourth, somewhat lesser form of amblyopia also exists. This condition is
termed ametropic or refractive amblyopia. In this situation, a large, uncorrected,
fairly symmetrical refractive error is present in both eyes, leading to poorly
formed images bilaterally. The childs visual acuity does not improve with the
placement of glasses initially, but generally does get better over time, eventually
reaching relatively normal levels.

Pathophysiology
Much of what is known at this time about the physical basis of amblyopia
comes from the pioneering work of Hubel and Wiesel, who studied the effects of
normal and abnormal visual experience in kittens. Flynn nicely summarized their
Nobel Prize winning work in his 1991 Costenbader lecture [3]. In their initial
experiment, the investigators sutured one eyelid shut shortly after birth, simulating form deprivation, and assessed the effect this had on vision when they
surgically opened the eye 10 weeks later. They discovered that there was little or
no electrical response in the cerebral cortex when images were viewed with the
previously sutured eye, whereas the electrical response from those cortical cells
driven by the normal eye were as expected. Histologically, marked shrinkage was
noted in the lateral geniculate nucleus of those cells associated with the deprived
eye. Similar results were obtained when the experiment was repeated in monkeys.
These findings did not occur when single eyelids of adult cats were sutured shut
or when both eyelids of the kittens were sewn shut. This finding led them to
postulate that, in the developing brain, there is a competition between both eyes
for cells in the visual cortex. Unequal visual input results in abnormal development of the brain, with cells anatomically destined to serve the closed eye
responding only to input from the open eye. This results in a reduction in the
number of cells receiving input from the deprived eye, as well as a reduction in
the number of binocularly driven visual cortical cells. No anatomic changes were
found in the retina or optic nerve.
Timing and duration of closing were critical; the earlier the manipulation
occurred and the longer it lasted, the more severe the cortical damage. In addition,
if the lids were simply opened afterwards in the affected kittens, and nothing else
was done, no recovery resulted. If, however, the eyelids of the fellow eye were
then sutured closed, recovery of vision could be seen in the previously closed
eye. This finding led to the development of the concept of the critical period of
visual development.
The critical period of visual development also applies to the human experience
[6]. Form deprivation, strabismus, and anisometropia can all cause amblyopia in
the infant and young child, but if the onset of these abnormalities occurs after age
7 to 8 years old, vision loss from amblyopia is no longer seen. The period during
which recovery from amblyopia can be obtained is somewhat longer in humans,

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and may, in some individuals, last into the teen-age years or even later [7 9].
The earlier amblyopia is recognized and treated, however, the more certain
the result.

Treatment
The treatment of amblyopia involves forcing the patient to fixate with the
amblyopic eye rather than the sound eye. This treatment is accomplished by
providing optimal conditions for use of the amblyopic eye: correcting any
underlying organic pathology, such as a cataract or corneal scar, and furnishing
the appropriate glasses or contact lenses, if a refractive error is present. Following
this correction, some form of artificial deprivation is employed to blur the image
in the good eye, forcing the patient to use the amblyopic one. In strabismic
amblyopia, however, aligning the eyes is not necessary before initiating amblyopia therapy. In fact, most clinicians feel that just the opposite is true; that is, the
elimination of amblyopia is the first step to treating strabismus successfully.
The mainstay of amblyopia therapy is occlusion of the sound eye with either
an opaque patch or contact lens or with a translucent filter over the fixing eye.
Reports of patching to treat strabismic amblyopia date back to at least 900 AD. In
a well-known treatise on the subject, Count de Buffon, a French naturalist and
botanist, recommended patching the fixating eye in strabismic amblyopia in
1743. This treatment was later abandoned, however, because amblyopia was
considered to be a fixed, congenital anomaly. It was not until the 1930s, when the
concept of amblyopia as a sensory adaptation to strabismus was developed, that
patching was once again reinstituted as a therapeutic modality [1,2].
Occlusion can be prescribed either full time or for part of the day, depending
on such factors as the age of the patient, visual needs such as school or sports,
and degree of amblyopia. In general, the older the patient and the more severe
the depth of vision loss, the longer the duration and intensity of patching that is
required. As previously discussed, the patient must also be carefully monitored
during this therapy because of the possibility that the patching itself might
induce occlusion amblyopia in the good eye. Thus frequent visits to the
ophthalmologist are required, especially in infants, to monitor the vision in
both eyes.
Another potential complication of patching occurs in the treatment of
anisometropic amblyopia when there is little or no strabismus present. Occasionally, the long-term application of a patch might adversely affect binocular
fusion in these patients, producing strabismus as an unintended consequence.
Most clinicians feel strongly that the benefit of restoration of vision warrants the
risk involved.
Penalization is another method of treating amblyopia. Penalization involves
the instillation of a cycloplegic agent that paralyzes accommodation, such as
atropine 1% or cyclopentolate ophthalmic solution, into the good eye to blur
vision and induce the child to fixate with the amblyopic eye. This technique is not

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as effective as full-time patching but can be successful if the fixating eye is

hypermetropic, and there is a mild to moderate vision deficit to overcome.
Penalization may also be of benefit in those children who are reluctant to comply
with occlusion therapy [10].

Prevention and screening

Successful treatment of amblyopia depends on timely recognition of amblyopia and those factors that may produce amblyopia. For this reason, the American
Academy of Ophthalmology, the American Association for Pediatric Ophthalmology and Strabismus, the American Academy of Pediatrics, the American
Academy of Family Physicians, and others recommend early vision screening to
detect treatable eye disease, notably amblyopia, in infancy and childhood [11]. A
summary of the recommendations of the American Academy of Pediatrics [12]
regarding vision screening and detection of amblyopia and other eye disease is
provided in another article.
Despite these recommendations, the American Academy of Pediatrics believes
that only 21% of preschool and younger children in this country are adequately
screened for amblyopia [13]. Many difficulties are encountered when performing
vision screening in the pediatric population. Infants and preverbal children are
unable to provide subjective responses to visual acuity testing and do not easily
cooperate with testing of ocular alignment or stereoacuity. The same is often true
of older children who are nonverbal or have developmental delay. Some
populations, particularly in underserved areas, might be difficult to reach for
vision screening. Therefore developing better techniques to screen large populations of children remains a public health challenge.
The ideal screening approach must be accurate, with both high sensitivity and
specificity. It should be easy to administer to large groups of children and should
also be reasonably inexpensive. One possible technologic answer to this problem
is photoscreening [13]. In this technique, a camera or video system is used to
capture the image of the pupil and red reflex. The child need only fixate on a
target for a few seconds to obtain an adequate photograph. The quality of the
image is then analyzed, either on site by the tester or at some remote location by
trained technicians or computerized analysis. Abnormal reflexes might indicate
the presence of amblyogenic factors, such as strabismus, media opacities, and
significant refractive errors.
The technology is still in the developmental phase, however, and most
techniques still exhibit relatively low sensitivity with high false-positive rates.
In addition, the equipment is still too expensive at this time to be cost effective in
the ophthalmologists or pediatricians office [14]. It is hoped that advances in
technology will lead to more accurate, cost-effective techniques to screen
preverbal children for those factors that could predispose them to the development of amblyopia. Once a child is old enough to cooperate with visual acuity
and stereopsis testing, however, carefully administered subjective tests are far

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superior in detecting vision defects than mass screening techniques and remain
the standard of care for the diagnosis of amblyopia.

Future developments
There is much room for improvement in the diagnosis and management of
patients with amblyopia. Better screening methods are being formulated for the
timely recognition of patients who are at risk for or who have already developed
amblyopia. Public health initiatives will be required to make this screening
available to all segments of society. In addition, large-scale clinical trials are
currently underway to determine the best method for treating established
amblyopia. For example, a recent study compared atropine to patching for the
treatment of moderate amblyopia and found no significant differences in efficacy
[10]. Improved techniques to ensure patient compliance will increase success
rates [9]. Finally, basic science research is looking at the molecular basis for the
neurophysiologic changes seen in amblyopia. The goal will be to modulate the
neuronal responses to abnormal visual input, either to prevent amblyopia when
known predisposing conditions are present or to treat long-established amblyopia
[15]. Pharmacologic agents such as levodopa and cytidine-50-diphosphocholine
have been shown to produce temporary improvement in vision in patients with
amblyopia [16 18]. Psychophysical perceptual learning techniques are also
currently being investigated as a means to correct amblyopia in adults [19]. It
is hoped that earlier and better treatment options will markedly reduce the
incidence of this serious ocular disorder.

Summary
Amblyopia is a serious medical condition affecting tens of millions of individuals around the world. For the most part it is correctable, assuming that it is
promptly recognized and vigorously treated. Amblyopia may result from form
deprivation, anisometropia, or strabismus in infants and young children. Basic
research in animal models has shown that the major pathologic changes in
amblyopia occur in the visual cortex of the brain. The mainstay of treatment
remains patching, although penalization has a role to play in the management of
moderate degrees of amblyopia. Better methods for early identification of patients
with amblyopia are being developed, along with newer novel methods of treatment.

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