Causes of horizontal strabismus in children

INTRODUCTION — Strabismus is the term used to describe an anomaly of ocular alignment (see "Evaluation and management of strabismus in children", section on 'Terminology'). The eye misalignment can involve either eye and can occur in any direction; it can be congenital or acquired, latent or manifest, constant or intermittent, and fixed or variable, depending upon the position of gaze and other factors.

Strabismus can be classified according to the direction of deviation: in (esodeviations), out (exodeviations), and up or down (vertical deviations). The causes of horizontal strabismus are reviewed here. The evaluation of strabismus and the causes of vertical strabismus are discussed separately. (See "Evaluation and management of strabismus in children" and "Causes of vertical strabismus in children".)

NEUROANATOMY — Three pairs of extraocular muscles move each eye in three directions: vertically (superior and inferior), horizontally (medially [adduction] and laterally [abduction]), and torsionally (intorsion when the eye rotates nasally and extorsion when the eye rotates temporally along the visual axis). The superior oblique muscle is innervated by cranial nerve IV, the lateral rectus muscle by cranial nerve VI, and all others by cranial nerve III (table 1).

The understanding of strabismus requires knowledge of the two major principles that govern ocular motility [1]:

●Agonist muscles in both eyes receive equal innervation to ensure coordinated binocular eye movements. Thus, when the right lateral rectus muscle is activated to abduct the right eye, the left medial rectus muscle is activated equally to adduct the left eye.

●Agonist/antagonist muscle pairs within each eye receive reciprocal innervation [2]. Thus, when the right medial rectus muscle contracts to adduct the right eye, its antagonist, the right lateral rectus muscle, relaxes.

ESODEVIATIONS — Deviations of the eye toward the nose, which are the most common type of strabismus in children, are called esodeviations. In one population-based cohort, the cumulative prevalence of esotropia among children younger than six years of age was 2 percent [3].

In children with an esodeviation, the corneal light reflection is displaced temporally in proportion to the degree of ocular deviation (figure 1) [4]. (See "Evaluation and management of strabismus in children", section on 'Corneal light reflex'.)

The most common causes of esodeviation include [5]:

●Accommodative esotropia

●Idiopathic infantile esotropia

●Duane syndrome

●Abducens palsy

●Sensory esotropia

Infants ≤4 months old who have constant esotropia and infants >4 months old who have persistent esodeviation (even if intermittent) should be referred to an ophthalmologist with expertise in children's eye care for evaluation because the esodeviation is unlikely to resolve spontaneously [6-8].

Accommodative esotropia — Accommodative esotropia is the most common cause of esotropia in children [5,9]. To focus properly on a near object, the ciliary muscle must alter the shape of the lens (accommodation) and both eyes must move inward (convergence). In children who have normal ocular alignment, accommodation is associated with a predictable and physiologic amount of convergence. In children who have accommodative esotropia, the physiologic convergence cannot be overcome by fusional divergence (ie, movement of the eyes away from each other to restore binocular vision) and, as a result, esotropia occurs (picture 1). Accommodative esotropia occurs more commonly in children who have hyperopia (farsightedness).

Clinical features — Accommodative esotropia most commonly presents in the second year of life but may rarely be present in children as young as three months of age [10] and can be diagnosed later in life. Early-onset accommodative esotropia appears to occur more commonly in premature infants [10]. At the time of onset, the crossing usually is intermittent and often more pronounced with near fixation than with distant fixation. Over time, the deviation can become more pronounced and constant. Amblyopia occurs in approximately 20 percent of patients with accommodative esotropia [10].

Treatment — Most patients with accommodative esotropia can achieve long-term stabilization of ocular alignment with cycloplegic refraction and prescription of hyperopic spectacles (picture 1) [9-13]. Bifocals are sometimes used to control the ocular alignment for near vision. However, fusion for distance fixation is often sufficient to maintain binocular function and some pediatric ophthalmologists do not use bifocals to control a residual near-deviation. Surgical correction of residual esodeviation may be necessary in some patients, more likely in those with delayed diagnosis and treatment [11,13]. Topical miotic agents (eg, phospholine iodide, diisopropyl fluorophosphate, carbachol) have been used by some practitioners to manipulate accommodation, but lack of availability, limited experience, and side effects limit use of these drugs.

Idiopathic infantile esotropia — Idiopathic infantile esotropia, or "congenital" esotropia, is another common type of childhood strabismus (picture 2). This esodeviation has onset before six months of age and occurs in children who are neurologically normal [9,14]. It is not caused by hyperopic refractive error. The theory is that there is a central anomaly of fusion, which is present at birth, although the esotropia may develop anytime in the first six months of life. The cause of this theoretic fusion anomaly remains unknown [15].

Clinical features — The esotropia of idiopathic infantile esotropia typically is a large-angle esotropia, usually greater than 25 to 30 prism diopters. Children who have idiopathic infantile esotropia sometimes turn their faces toward the fixing eye, which is preferably positioned in adduction (cross-fixation). Thus, the right eye views objects in the left visual field and vice versa [14]. Cross-fixation is most commonly seen in children with very large deviations. Idiopathic infantile esotropia is associated with a variety of other ocular motility abnormalities that may be present at diagnosis or may develop later in childhood. Other ocular motility abnormalities can develop despite surgical therapy of the esotropia and initial good ocular alignment [16,17]. The most common of these abnormalities include [18-20]:

●Overelevation in adduction, which is characterized by anomalies of eye movement in side gaze and other complex abnormalities of eye movement

●Dissociated strabismus complex, which refers to a latent tendency of one eye to deviate upward and outward during daydreaming or when fixation is disrupted (eg, by occluding one eye)

●Latent nystagmus, which refers to nystagmus that occurs (or worsens) when one eye is occluded

●Amblyopia, which may develop in as many as 17 to 50 percent of affected children [20,21]

Ophthalmologic history and examination usually can help the clinician distinguish idiopathic infantile esotropia from the other causes of esodeviation. Duane syndrome and Moebius syndrome are present at birth, whereas idiopathic infantile esotropia typically has onset during the first six months of life but is rarely present at birth. In addition, children with Duane syndrome usually have a smaller-angle esotropia (usually less than 20 to 30 prism diopters) [22] and those with Moebius syndrome usually have involvement of the facial and other cranial nerves. Children who have infantile esotropia usually have a low refractive error, whereas those with accommodative esotropia usually have moderate to high hyperopia, and those with sensory esotropia have poor vision in the affected eye, usually because of an anatomic abnormality.

Idiopathic infantile esotropia may be particularly difficult to differentiate from congenital or early-onset abducens palsy because infants who have idiopathic infantile esotropia and large deviations may have difficulty abducting one or both eyes because of secondary contracture of the medial rectus muscle(s) (see "Sixth cranial nerve (abducens nerve) palsy", section on 'Evaluation'). Oculocephalic testing, with or without monocular occlusion, may be helpful in making this distinction. Furthermore, abduction velocity (saccades) can usually be documented to be brisk in patients with idiopathic infantile esotropia but not in those with abducens palsy. Distinguishing between the two disorders is important because the evaluation and treatment may differ.

Treatment — The first step in the treatment of children with idiopathic infantile esotropia is to maximize visual acuity by treatment of amblyopia if it is present. Surgery designed to strengthen or weaken the extraocular muscles is the mainstay of therapy. The procedure most commonly performed is designed to weaken the medial rectus muscle(s). It is most commonly performed in both eyes. Successful ocular alignment initially is achieved in the majority of children [6]. However, many children later develop recurrent esotropia, consecutive or secondary exotropia, or other eye movement abnormalities associated with the esotropia syndrome [23]. Earlier realignment appears to be associated with better sensory outcome [24].

Injection of botulinum neurotoxin (BoNT) into the medial rectus muscle of one or both eyes also has been used to treat idiopathic infantile esotropia. BoNT creates temporary paresis of the medial rectus muscle. More than one injection is needed in most children. Long-term improvement may result from changes in the rectus muscle's length/tension relationships or in the child's fusional capacity during the temporary paralysis [25]. In a randomized trial comparing reoperation and botulinum toxin injection in 55 children who failed initial surgical treatment, the long-term outcomes were similar [26,27].

Duane syndrome — Duane syndrome, also called Duane retraction syndrome or the Stilling-Türk-Duane syndrome, is a congenital strabismus that is caused by failure of normal development of the abducens nerve (the sixth cranial nerve) followed by anomalous innervation of the lateral rectus muscle by the oculomotor nerve [22,28-34]. Patients with Duane syndrome may have esotropia or exotropia, and the following classification system is commonly utilized [22,35]:

●Type I (esotropic Duane syndrome) – Patients have difficulty with abduction of the affected eye (picture 3) (70 to 80 percent of cases).

●Type II (exotropic Duane syndrome) – Patients have difficulty with adduction of the affected eye (picture 4) (7 percent of cases).

●Type III – Patients have difficulty with both abduction and adduction (picture 5) (15 percent of cases). These patients can have esotropia or exotropia in the primary position.

Most cases of Duane syndrome are sporadic, but an autosomal dominant inheritance pattern has been described. Genetic loci have been mapped to chromosomes 8q13 and 2q31 [30,36-38]. Duane syndrome may be seen in association with other conditions, including Klippel-Feil anomaly, hemifacial microsomia, and Wildervanck syndrome [39].

Clinical features — Duane syndrome affects the left eye in 59 percent of cases, the right in 23 percent, and both in 18 percent [28,39]. Familial cases usually are bilateral [40]. The angle of deviation typically is small (<20 to 30 prism diopters) [22]. One of the characteristic features of Duane syndrome is the retraction of the globe (producing positional enophthalmos) and narrowing of the palpebral fissure during attempted adduction (picture 3). This feature is caused by the simultaneous contraction of the medial and lateral rectus muscles that occurs during attempted adduction. Some patients with Duane syndrome may have normal ocular alignment in the straight-ahead (or primary) position and manifest deviation of the eyes only in the lateral-gaze positions.

Other clinical features may include abnormal turn of the head to permit fusion and may include upshoot and/or downshoot of the affected eye in adduction. These movements are thought to be caused by a "leash" phenomenon of the lateral rectus muscle or aberrant innervation of the vertical rectus muscles. Patients with Duane syndrome also may have amblyopia and unequal refractive errors (anisometropia). Extraocular features associated with Duane syndrome include thenar hypoplasia and radial ray abnormalities, deafness, and fusion of the second and third cervical vertebrae [28,41].

Treatment — The treatment of Duane syndrome is similar to that of other forms of strabismus. Indications for strabismus surgery include:

●Strabismus in the primary position of gaze (straight ahead)

●Abnormal head posture

●Significant upshoot or downshoot of the eye in adduction

●Significant enophthalmos in adduction

Abducens nerve palsy — Paralysis of the sixth cranial nerve (abducens nerve) is an uncommon cause of esotropia in children. Deviation in children with abducens nerve palsy increases with gaze toward the affected side and decreases with gaze toward the unaffected side [4]. Abducens nerve palsy in children is discussed separately. (See "Sixth cranial nerve (abducens nerve) palsy".)

Sensory esotropia — Sensory esotropia may occur in children of any age. Sensory esotropia results when vision in the affected eye is sufficiently poor that fixation and eye alignment cannot be maintained. Sensory eye deviation can be caused by congenital or early-onset cataract, optic nerve anomalies, retinal detachment, retinoblastoma, and any other disease or injury that results in poor vision in an eye. Esotropia is the second most common presenting sign in patients with retinoblastoma (after leukocoria) [42]. (See "Vision screening and assessment in infants and children" and "Cataract in children" and "Congenital and acquired abnormalities of the optic nerve" and "Retinoblastoma: Clinical presentation, evaluation, and diagnosis", section on 'Clinical presentation'.)

Moebius syndrome — Moebius syndrome is a rare cause of esotropia. Patients with Moebius syndrome have unilateral or bilateral anomalies of multiple cranial nerves, including the facial nerve and the abducens nerve [43,44]. Two genetic loci have been mapped: one at 13q12.2-q13 [45,46] and the other at 3q21-q22 [47]. Moebius syndrome may occur in association with the Poland anomaly, which consists of absence of the pectoralis major muscle and limb abnormalities [48], or as a result of in utero exposure to misoprostol [49].

Clinical features — Patients with Moebius syndrome typically present with facial diplegia and thus absence of facial expression. Feeding difficulties may be present if the ninth cranial nerve (the glossopharyngeal nerve) is involved. Other variably present manifestations include peripheral neuropathy, intellectual disability, arthrogryposis, limb deficiencies, flexion finger contractures, and hypogonadotropic hypogonadism [43,44,50].

Treatment — The treatment for the strabismus associated with Moebius syndrome is the same as for other forms of strabismus. Indications for strabismus surgery include:

●Strabismus in the primary position of gaze (straight ahead)

●Abnormal head posture

In addition, those patients with involvement of the facial nerve require observation for corneal exposure and treatment if present.

EXODEVIATIONS — Horizontal ocular deviations in which the visual axis deviates outward are called exodeviations. Children with exodeviations typically present during the first decade of life. The prevalence is approximately 1 percent in children younger than 11 years [51]. In children who have moderate to large exodeviation, the corneal light reflex appears in the center of the fixating eye and is displaced nasally in the deviated eye (figure 1). The most common cause of exodeviation in children is intermittent exotropia [51,52]. Other causes include type II Duane syndrome, oculomotor nerve paresis, congenital fibrosis of the extraocular muscles (CFEOM), sensory exotropia (related to decreased visual acuity in one eye), and consecutive exotropia (exotropia after surgery to correct esotropia). (See 'Duane syndrome' above.)

Intermittent exotropia — Intermittent exotropia is the most common exodeviation of childhood, affecting almost 1 percent of the general population [53]. The typical onset occurs when the child is two to three years of age [4].

Clinical features — Children with intermittent exotropia usually present with a complaint that one eye "floats" or "drifts" when the child is tired or inattentive. In the early stages of this condition, affected children may be able to control the deviation and realign their eyes when their attention is brought to the problem. They may need to blink to help reestablish fusion, and excessive blinking may be the presenting complaint [54].

The child with intermittent exotropia may have normal ocular alignment and no obvious problems at the initial clinical examination. With progression, the ocular deviation is more difficult for the child to control and tends to become manifest more frequently. Children with intermittent exotropia usually do not experience diplopia, because the developing visual system of the child suppresses the unwanted image from the deviating eye, when the eye is deviating. The risk of developing amblyopia is lower than in children with esotropia. In one population-based study, more than 90 percent of children with intermittent exotropia developed myopia by the age of 20 years whether or not they were treated surgically [55].

Most patients with intermittent exotropia can be categorized according to the degree of exodeviation with distance fixation versus near fixation [56]:

●Basic exotropia is the term used to describe an exodeviation that is approximately the same size at distance compared with near fixation

●Divergence excess-type exotropia is present when the exodeviation is greater at distance compared with near fixation

●Convergence insufficiency-type exotropia is present when the exodeviation is greater at near compared with distance fixation (picture 6)

Convergence insufficiency may be associated with asthenopia (ie, eye strain) or diplopia with reading or schoolwork. It also is a common finding in presbyopic adults who require bifocals to read.

Treatment — A variety of treatments have been proposed for intermittent exotropia. However, no single treatment has proven superior for all cases and long-term follow-up demonstrates a high recurrence rate regardless of initial therapy [9,57,58].

Observation — Observation is an acceptable approach to managing patients who are otherwise asymptomatic and who are able to control their exodeviation most of the time. This approach should include monitoring for any of the following associated problems or symptoms:

●Amblyopia

●Headache

●Eye strain

●Double vision

●Closing of one eye in sunlight (eg, monocular manifest deviation)

●Increasing frequency of deviation

As a general rule, the prognosis for normal binocular vision and stereopsis is good if the exotropia is manifest infrequently. Intervention for children with intermittent exotropia should be determined on a case-by-case basis at the discretion of the clinician and the parents.

Vision therapy — Intervention can be passive or active:

●Passive vision therapy (patching) – Passive vision therapy is typically used in younger children who are not developmentally mature enough to participate in active vision therapy. It consists of alternate part-time occlusion (patching) of one eye with the aim of preventing or reducing suppression. In a randomized trial comparing part-time patching to observation in 201 young children with intermittent exotropia, deterioration over six months was uncommon in both groups (2.2 versus 4.6 percent, respectively; nonsignificant) [59]. Control of exotropia as assessed by a six-point score was slightly better with patching (mean score 2.3 versus 2.8), though this finding is not likely to represent a clinically meaningful difference. A similar trial in older children (ages 3 to <11 years) found that part-time patching reduced the rate of deterioration over six months; however, deterioration was uncommon in both groups (0.6 percent in the patching group versus 6.1 percent in the observation group) [60]. As with all treatments for intermittent exotropia, failure and recurrence after discontinuation of therapy are common [58].

Another method of passive vision therapy that has been used for intermittent exotropia is prescription of myopic spectacles (over-minus lenses). It was thought that over-minus lenses might improve control of intermittent exotropia by stimulating accommodation and accommodative convergence. However, a 12-month randomized trial in children ages 3 to 10 years demonstrated that while over-minus spectacles improved control of distance exotropia during the trial (ie, while wearing the over-minus spectacles), the benefit was not maintained after treatment was tapered off and it was associated with increased myopic shift [61]. Thus, we suggest not prescribing over-minus lenses for this purpose.

●Active vision therapy (orthoptics) – Active vision therapy (also referred to as orthoptics) involves a combination of eye exercises and vision-training maneuvers aimed at improving convergence and/or divergence amplitudes, improving fusion strength, and maintaining single binocular vision [62]. This treatment is often provided in the office of an optometrist with experience in vision therapy; reinforcing exercises are then done at home in between office-based sessions. Alternatively, it be done entirely at home using computer-generated orthoptic exercises.

In a randomized controlled trial of 221 children (aged 9 to 17 years), an intensive program of office-based vision therapy with home reinforcement was more effective in reducing signs and symptoms than several home-based therapies [63]. "Active" vision therapy consisted of a rigorous protocol, including a variety of exercises designed to improve vergence and accommodation. The control intervention consisted of home-based procedures that simulated orthoptic exercises but that did not actually include vergence or accommodation training.

Although this study suggests that intensive office-based vision therapy is superior to home therapy without binocular vision training activities, additional studies are needed to determine whether office-based therapy is superior to equally intensive home-based therapy [64].

Strabismus surgery — Strabismus surgery is the treatment used most often by ophthalmologists for advanced intermittent exotropia [65]. Surgical guidelines typically recommend intervention when the exodeviation is manifest frequently and/or if the patient is symptomatic. The surgery involves weakening the lateral rectus muscles of both eyes, weakening (recession) the lateral rectus muscle and tightening (resection) the medial rectus muscle in a single eye, or strengthening the medial rectus muscles in both eyes. All procedures are similarly effective depending on the type and magnitude of exodeviation. Recurrence occurs commonly after surgery for intermittent exotropia. (See "Evaluation and management of strabismus in children", section on 'Overview of management'.)

Oculomotor nerve palsy — The oculomotor nerve provides efferent innervation to four extraocular muscles (the medial rectus, superior rectus, inferior rectus, and inferior oblique), and the levator palpebral superioris muscle of the eyelid. It also innervates the pupillary constrictor muscle, via its parasympathetic component (table 1).

Complete oculomotor palsy presents with the classic triad (figure 2):

●Exotropia and hypotropia of the involved eye

●Mydriasis

●Complete ptosis

The presentation of incomplete oculomotor paresis varies depending upon which muscle(s) are affected. Clinical findings may include deficits in elevation or depression, ptosis, and anisocoria, with a larger pupil on the involved side. In contrast with other forms of exodeviation, the exodeviation of oculomotor nerve palsy or paresis is associated with reduced ability (or inability) to adduct the affected eye. These patients may use an anomalous head position to maintain fusion. (See "Third cranial nerve (oculomotor nerve) palsy in children", section on 'Clinical manifestations'.)

Patients who are suspected of having oculomotor nerve palsy should be referred to a pediatric ophthalmologist who is skilled in the evaluation and management of ocular motility abnormalities. Neuroimaging may be necessary to determine the underlying etiology (table 2). (See "Third cranial nerve (oculomotor nerve) palsy in children", section on 'Evaluation'.)

Congenital fibrosis of the extraocular muscles — CFEOM can mimic third-nerve palsy. CFEOM has several phenotypes: FEOM1 and FEOM3 cause hypodeviations, whereas FEOM2 causes exotropia. FEOM2 is characterized by bilateral ptosis with the eyes fixed in an exotropic position [66]. This autosomal recessive disorder is caused by mutations in the ARIZ gene on chromosome 11q13, which codes a transcription factor protein that is required for development of the third and fourth cranial nerves in the mouse and zebrafish [67,68]. Neuropathologic changes suggest that FEOM2 is caused by a primary defect in the superior and inferior divisions of the oculomotor nerve [66].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

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 info" and the keyword[s] of interest.)

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

SUMMARY AND RECOMMENDATIONS

●Esodeviations – Esodeviations (deviations of the eye toward the nose) are the most common type of strabismus in children. In moderate to large esodeviations, the corneal light reflex appears approximately in the center of the fixating eye's pupil and is displaced temporally in the deviated eye (figure 1). (See 'Esodeviations' above.)

•Referral – Infants ≤4 months old who have constant esotropia and infants >4 months old who have persistent esodeviation (even if intermittent) should be referred to an ophthalmologist with expertise in children's eye care for evaluation because the esodeviation is unlikely to resolve spontaneously.

•Causes – The most common causes of esodeviation include:

-Accommodative esotropia (see 'Accommodative esotropia' above)

-Idiopathic infantile esotropia (see 'Idiopathic infantile esotropia' above)

-Duane syndrome (see 'Duane syndrome' above)

-Abducens palsy (see 'Abducens nerve palsy' above)

-Sensory esotropia (see 'Sensory esotropia' above)

●Exodeviations – Exodeviations (outward deviations of the eye) typically present during the first decade of life. In moderate to large exodeviation, the corneal light reflex appears approximately in the center of the fixating eye and is displaced nasally in the deviated eye (figure 1). (See 'Exodeviations' above.)

•Intermittent exotropia – Intermittent exotropia is the most common exodeviation in childhood, affecting almost 1 percent of the general population. The typical onset is at two to three years of age. Affected children usually present with a complaint that one eye "floats" or "drifts" when the child is tired or inattentive. Management options include observation, vision therapy (eg, patching or orthoptics), or in advanced cases, strabismus surgery. (See 'Intermittent exotropia' above.)

•Other causes – Other causes of exodeviations in children include:

-Type II Duane syndrome (see 'Duane syndrome' above)

-Oculomotor nerve paresis (see 'Oculomotor nerve palsy' above)

-Congenital fibrosis of the extraocular muscles (CFEOM) (see 'Congenital fibrosis of the extraocular muscles' above)

-Sensory exotropia (similar to sensory esotropia but with outward rather than inward deviation) (see 'Sensory esotropia' above)

-Consecutive exotropia (exotropia after surgery to correct esotropia)