Amblyopia in children: Classification, screening, and evaluation

INTRODUCTION — Amblyopia is a functional reduction in visual acuity caused by abnormal visual development early in life. It is the most common cause of pediatric visual impairment, occurring in 1 to 4 percent of children. Early detection of amblyopia and/or amblyopia risk factors facilitates earlier treatment, which improves visual outcomes [1-4]. This is the basis for screening preschool-age children for vision problems and amblyopia. (See 'Screening' below and "Vision screening and assessment in infants and children", section on 'Vision screening'.)

The definition, classification, and evaluation for amblyopia is reviewed here. The management and outcome of amblyopia are reviewed separately. (See "Amblyopia in children: Management and outcome".)

Vision assessment, strabismus, and refractive errors in children are also discussed separately:

●(See "Vision screening and assessment in infants and children".)

●(See "Evaluation and management of strabismus in children".)

●(See "Refractive errors in children".)

DEFINITION — Amblyopia is a functional reduction in visual acuity caused by abnormal visual development early in life. It is a secondary consequence of early vision disturbance by strabismus or other amblyopia-inducing conditions during the critical period for visual development. The disorder is predominantly unilateral, though occasionally both eyes may be affected. It is often associated with impaired or absent stereoacuity (fine depth perception) [5].

●Unilateral amblyopia is defined as a difference in visual acuity between eyes that is ≥2 lines on a standard vision chart (eg, 20/20 in the left eye and 20/30 in the right eye).

●Bilateral amblyopia (also known as ametropic or isoametropic amblyopia) is defined as visual acuity worse than 20/40 in both eyes (in children ≥4 years) or visual acuity worse than 20/50 in both eyes (in children ≤3 years) in the setting of severe uncorrected refractive error in both eyes [6].

These definitions, however, have certain limitations. Most notably, it is important to recognize that measuring visual acuity in very young children by traditional methods is usually not possible. Estimation of visual acuity in preliterate young children and diagnosis of amblyopia require eye examination by a skilled eye care specialist.

ETIOLOGY AND CLASSIFICATION — Amblyopia results from disturbances in visual development early in life. The period of visual cortex neuroplasticity is the critical period during which the visual system is affected by outside influences. Appropriately focused visual stimuli are crucial to the development of normal vision. Visual acuity typically reaches the adult level by three to five years of age. The period during which visual deprivation may cause amblyopia extends for a longer period of time, from a few months of age to approximately seven to eight years of age [7]. (See "Vision screening and assessment in infants and children", section on 'Visual development'.)

Amblyopia is classified by the underlying cause of the visual disturbance [8].

Strabismic amblyopia — Strabismus is the misalignment of the eyes. Strabismic amblyopia results from the abnormal binocular interaction that is present in patients with strabismus. This abnormal interaction occurs because the foveas of the two eyes are presented with two different images. The visual cortex suppresses the image from one eye in order to avoid having diplopia and visual confusion; long-term suppression of one eye can result in strabismic amblyopia.

Amblyopia does not develop in all children with strabismus. In children with intermittent strabismus (eg, intermittent exotropia), the images presented to the foveas can be fused a large proportion of the time, which prevents the development of amblyopia in most children. In children with constant strabismus, alternate fixation (ie, sometimes with the right eye and sometimes with the left) may also prevent the development of amblyopia. (See "Evaluation and management of strabismus in children".)

Refractive amblyopia — Refractive amblyopia most commonly occurs as a result of asymmetric refractive error (anisometropia) between the child's two eyes. In anisometropic amblyopia, the foveas of the two eyes are presented with different image clarity due to unequal uncorrected refractive errors. In general, one image is well focused while the other is not. Amblyopia may develop in the eye with the unfocused image. Bilateral refractive amblyopia (called ametropic or isoametropic amblyopia) is less common and develops when there is severe uncorrected refractive error in both eyes.

Refractive amblyopia occurs most commonly in hyperopic patients, but it may occur in patients with severe myopia or astigmatism. (See "Refractive errors in children".)

Refractive amblyopia is often detected at an older age than strabismic amblyopia, because children with refractive amblyopia lack obvious external abnormalities of the eyes. Their visual functioning appears normal because they typically see well with the one eye. Affected children are often diagnosed during vision screening when they are old enough to identify letters or figures (typically four to five years). Photoscreening and autorefraction, which are reliable methods to perform vision screening in younger nonverbal or preliterate children, may lead to earlier detection. (See "Vision screening and assessment in infants and children", section on 'Instrument-based screening'.)

Deprivation amblyopia — Deprivation amblyopia is the least common and most severe type of amblyopia. It results from vision deprivation, typically a result of interruption of the visual axis or severe distortion of the foveal image. Cataracts, ptosis, corneal opacities, and vitreous hemorrhage may cause deprivation amblyopia [9,10]. Bilateral high refractive errors can also result in bilateral deprivation amblyopia. Deprivation amblyopia in infancy results in permanent visual impairment if it is not treated urgently. (See "Cataract in children", section on 'Complications'.)

EPIDEMIOLOGY — The prevalence of amblyopia is estimated to be between 1 and 4 percent [5,11-18]. Estimates of prevalence vary by the threshold used to define reduced visual acuity, the population being studied, and the process of early screening and treatment [17,19-21].

Reported relative frequencies of each type of amblyopia are as follows [22]:

●Strabismic – Approximately 50 percent of cases

●Refractive – Approximately 15 to 20 percent of cases

●Combined mechanism (strabismus and refractive) – Approximately 30 percent of cases

●Deprivation – Less than 5 percent of cases

Amblyopia occurs with equal frequency in boys and girls [23]. In some series, the left eye was more commonly affected than was the right, particularly in cases of anisometropic amblyopia [23].

The mean age at presentation of amblyopia varies by the type [23,24]. In a series of 961 children, the mean ages of presentation for strabismic, refractive, and combined amblyopia were 3.3, 5.6, and 4.4 years, respectively [23]. The reported upper age limit at which amblyopia may develop after exposure to an amblyopia-inducing condition (eg, traumatic cataract) is approximately six to eight years [7,25].

The following factors have been reported to be associated with an increased risk of amblyopia [26]:

●Prematurity

●Small size for gestational age

●First-degree relative with amblyopia

●Neurodevelopmental delay

SCREENING — We recommend screening to detect amblyopia in all children younger than five years of age in accord with the American Academy of Pediatrics, American Academy of Family Physicians, and United States Preventive Services Task Force [27-29].

Screening includes vision risk assessment at all health maintenance visits and vision screening at three, four, and five years of age (table 1A-B). Vision screening in children is discussed in detail separately. (See "Vision screening and assessment in infants and children", section on 'Vision screening'.)

Early detection and treatment of amblyopia improves the prognosis for vision development [1-4]. Observational studies have shown that screening and early treatment of amblyopia and amblyopia-inducing risk factors in young children is associated with reductions in the prevalence and severity of amblyopia [19,30].

EVALUATION — Amblyopia should be suspected if the vision in the two eyes is unequal [6]. The testing used to diagnose amblyopia depends upon the age of the child (table 1B).

Preverbal children — Equality of vision between the eyes in preverbal children is assessed with several simple tests, which can be performed in the primary care office setting:

●Fixation reflex – Testing of the fixation reflex involves moving a visual target to and fro in the child's visual space. Each eye is tested separately by occluding the fellow eye. Accuracy is improved if the fixation test is repeated several times. (See "Vision screening and assessment in infants and children", section on 'Fixation reflex'.)

Children who have strabismus and equal vision can maintain steady fixation with either eye and typically do not have a strong fixation preference for one eye. Conversely, children with strabismus and amblyopia will rarely maintain fixation with the amblyopic eye when both eyes are uncovered. Detection of unequal vision is more difficult in nonverbal children who do not have strabismus, but the following tests are helpful.

●Objection to occlusion – The occlusion objection test involves monitoring the child's response to alternate occlusion of the eyes. Children with equal vision should respond equally, or not at all, to occlusion of either eye. Children with moderate-to-severe visual impairment in one eye typically become irritable when the eye with better vision is occluded (picture 1).

The test should be repeated several times because some children become agitated and resist attempts to cover either eye. A strong preference for one eye, indicated by objecting to its occlusion, is highly suggestive of amblyopia in the opposite eye.

●Vertical prism test – The vertical prism test uses a 10- to 14-prism-diopter vertical prism to induce a vertical tropia that facilitates the detection of unequal vision in preliterate children without strabismus [31]. The test is performed by first holding the prism (with the base down) in front of the child's right eye, which causes the image viewed by this eye to be higher than that of the left eye and resulting in a functional vertical tropia. Amblyopia should be suspected if the eyes move upward consistently to view the displaced image. This signifies that the patient prefers (ie, has better vision) in the right eye. The test then is repeated with the prism in front of the left eye to confirm this result. If, when the base down prism is placed before the left eye, there is no upward movement of the eyes, then this signifies that the patient prefers using the right eye.

Vision is thought to be equal if the child is able to maintain fixation with either eye and shows no preference for one displaced image over the other. Although the test is simple to perform in any setting, pediatric health care providers rarely perform the vertical prism test because they lack the necessary equipment. In addition, studies have shown that the results of fixation preference testing do not always correlate with formal visual acuity testing results [32,33].

Children >3 years — Accurate assessment of visual acuity can be made in cooperative verbal children. Visual acuity testing with optotypes should be attempted in all children older than three years. In the absence of an anatomic abnormality of the eyes, a best corrected visual acuity difference of ≥2 lines between the eyes (eg, 20/20 in the left eye and 20/30 in the right eye) indicates the presence of amblyopia in the poorer performing eye. (See "Vision screening and assessment in infants and children", section on 'Optotype tests'.)

Allen figure cards and other picture optotype tests typically are used to test the vision of younger children or children who are unable to cooperate with testing using the Snellen chart or the tumbling E figures. Allen figures frequently overestimate visual acuity in children with amblyopia. For this reason, Allen cards should be used only when other testing measures are not possible and should be used in conjunction with the vertical prism test. Amblyopia should be suspected when an acuity difference of one line between the eyes is found when Allen cards are used (eg, 20/30 in the left eye and 20/40 in the right).

Using a row of targets rather than a single optotype provides a more accurate assessment of visual acuity and improves detection of amblyopia. The "crowding phenomenon" refers to achievement of better visual acuity when optotypes are presented in isolation than when they are presented in a row or with surrounding crowding bars (figure 1). Crowding has minimal effect on visual acuity in a normally sighted eye; however, it may create substantial disturbance for the amblyopic eye resulting in lower visual acuity [34]. (See "Vision screening and assessment in infants and children", section on 'Crowding phenomenon'.)

REFERRAL INDICATIONS — Children with suspected amblyopia should be referred to an ophthalmologist or optometrist who is appropriately trained and experienced in evaluating children. Indications for referral include (table 1A):

●Visual acuity worse than 20/40 in a child 3 to 5 years of age or worse than 20/30 in a child ≥6 years

●Visual acuity difference of ≥2 lines between eyes on a standard vision chart (eg, 20/30 in the left eye and 20/40 in the right)

●Abnormal ocular alignment (ie, strabismus) (see "Evaluation and management of strabismus in children")

●Abnormal red reflex (see "Approach to the child with leukocoria")

●Asymmetry of vision (eye preference)

●Unilateral ptosis or other lesions that threaten the visual axis (eg, eyelid hemangioma)

Additional referral indications are discussed separately. (See "Vision screening and assessment in infants and children", section on 'Referral indications'.)

DIFFERENTIAL DIAGNOSIS — Amblyopia is a functional reduction in visual acuity that is a secondary consequence of strabismus, uncorrected refractive error, or structural obstruction to the visual pathway during early life. In the absence of one of these amblyopia-inducing conditions, alternative causes of reduced visual acuity must be considered (table 2). Alternative causes of vision loss should also be considered if a child with amblyopia fails to demonstrate improvement in visual acuity despite adherence to the treatment regimen.

Primary disorders of the visual pathway (including retina, optic nerve, and brain lesions) can generally be distinguished from amblyopia based upon the presence of any of the following findings:

●Leukocoria on physical examination (see "Approach to the child with leukocoria")

●Afferent pupillary defect (Marcus-Gunn pupil), which suggests an abnormality of the optic nerve (see "Congenital and acquired abnormalities of the optic nerve")

●Abnormal color vision in the affected eye, which may suggest an optic nerve lesion or retinal abnormality (see "Vision screening and assessment in infants and children", section on 'Color vision testing')

●Abnormalities of the retinal or optic nerve on dilated funduscopic examination

In addition, functional vision loss may be seen in children with anxiety or emotional disturbances. It is often associated with other somatic complaints, including headache, photophobia, or diplopia, which are not typical in patients with amblyopia. (See "Diagnostic approach to acute vision loss in children", section on 'Functional visual loss'.)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Crossed eyes and lazy eye (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Amblyopia is the functional reduction in visual acuity caused by abnormal visual development early in life. It is a secondary consequence of early vision disturbance during the critical period for visual development. (See 'Definition' above.)

●Etiology and classification – Amblyopia is classified into three main types based upon the underlying amblyopia-inducing condition (see 'Etiology and classification' above):

•Strabismic – Caused by abnormal alignment of the eyes (see 'Strabismic amblyopia' above)

•Refractive – Caused by unequal focus between eyes or severe uncorrected refractive error in both eyes (see 'Refractive amblyopia' above)

•Deprivation – Caused be structural abnormalities of the eye that obscure incoming images (see 'Deprivation amblyopia' above)

●Vision screening – All children <5 years old should undergo routine vision screening to detect amblyopia. Early detection and treatment of amblyopia improves the prognosis for normal vision development. Screening includes vision risk assessment at all health maintenance visits and vision screening at three, four, and five years of age. Recommendations for vision screening in children are summarized in the tables (table 1A-B) and discussed in detail separately. (See "Vision screening and assessment in infants and children", section on 'Vision screening'.)

●Evaluation – Amblyopia should be suspected if the vision in the two eyes is unequal or if the child has an amblyopia-inducing condition (eg, strabismus, asymmetric refractive error, cataract, ptosis). The testing used to diagnose amblyopia depends upon the age of the child (table 1B). In preverbal children, asymmetry of vision may be indicated by an abnormal fixation reflex or occlusion objection test (picture 1). In older children, asymmetric vision is detected through formal visual acuity testing. (See 'Evaluation' above.)

●Referral – Children with suspected amblyopia should be referred to an ophthalmologist or optometrist who is appropriately trained and experienced in treating children. Criteria for referral include (table 1A) (see 'Referral indications' above):

•Visual acuity worse than 20/40 in a child 3 to 5 years of age or worse than 20/30 in a child ≥6 years

•Visual acuity difference of ≥2 lines between eyes on a standard vision chart (eg, 20/30 in the left eye and 20/40 in the right)

•Abnormal ocular alignment (ie, strabismus) (see "Evaluation and management of strabismus in children")

•Abnormal red reflex (see "Approach to the child with leukocoria")

•Asymmetry of vision (eye preference)

•Unilateral ptosis or other lesions that threaten the visual axis (eg, eyelid hemangioma)

●Differential diagnosis – Alternative causes of reduced visual acuity (table 2) should be considered in children with apparent amblyopia who do not have an associated amblyopia-inducing condition (ie, strabismus, refractive error, or structural obstruction of the visual pathway). Alternative causes of vision loss should also be considered if a child with amblyopia fails to demonstrate improvement in visual acuity despite adherence to the treatment regimen. (See 'Differential diagnosis' above.)