Robert W. Enzenauer, Mary Ellen Hoehn, and Monte A. Del Monte
Strabismus is the term used to describe any ocular misalignment. The term originates from the Greek strabismus, meaning to “look askance” or the “evil eye.” Ocular misalignment that is constantly present and not controlled by fusional mechanisms is termed a tropia. A phoria is defined as a latent deviation that is controlled by fusional mechanisms and only present when one eye is blocked or covered. An intermittent tropia is a deviation that may sometimes be latent and controlled by fusional mechanisms (ie, a phoria) but may at other times be spontaneously manifest, often with illness or fatigue. Most children with strabismus develop a deviation that manifests mostly in one eye (the nondominant eye). Some strabismic children are able to switch fixation, using one eye at times and the other eye at other times, so that the strabismus will appear to shift from one eye to the other. This is termed alternating strabismus. In some children, strabismus develops as a result of poor vision in one eye and is termed sensory strabismus. Strabismus may also be the presenting sign of a life-threatening disease (eg, brain tumors with cranial nerve palsy) or vision-threatening conditions such as retinoblastoma or cataract.
Strabismus affects between 1% and 4% of children. The two most common types of strabismus are esotropia (cross-eyes, convergent squint, inwardly turned eyes) and exotropia (walleyes, divergent squint, outwardly turned eyes). Strabismus has been shown to occur in families and is noted more frequently among those children who have other neurological or medical conditions, including those affected by prematurity, low birth weight, cerebral palsy, intrauterine infection or drug exposure, craniofacial abnormalities, Down syndrome, and other genetic disorders.
Amblyopia develops in as many as 50% of children with strabismus.1 Early diagnosis and treatment of strabismus is therefore crucial to developing optimal, binocular visual function. Brief periods of intermittent esotropia or exotropia may be commonly observed during the first 2 to 3 months of life. This does not require referral to an ophthalmologist. However, any ocular misalignment after 3 months of age should be referred to an ophthalmologist for further evaluation. Likewise, any large or constant deviation should never be considered normal.
In addition to defining strabismus by the direction of the misalignment, it can also be categorized by the consistency of the amount of misalignment in different positions of gaze. A comitant strabismus is one in which the ocular misalignment is the same magnitude (measured by the ophthalmologist in units called prism diopters) in primary (straight-ahead gaze), left, right, up, and down gaze. All of the esotropias and exotropias discussed below are comitant. When one or more muscle(s) is paretic or restricted, the amount of strabismus will differ depending on the position of gaze. This is called an incomitant strabismus. Although nearly every paretic vertical strabismus (most commonly a superior oblique [cranial nerve IV] palsy) starts out incomitant (different in different gazes), it often becomes comitant over time. When strabismus is incomitant, the patient may adopt an anomalous head position to put the eyes in a position of gaze where they are most aligned while looking straight ahead. If patching of one eye eliminates the anomalous head position, an ocular cause is likely responsible and referral to an ophthalmologist is indicated.
There are many potential benefits to correcting strabismus.2 Strabismus surgery is reconstructive rather than cosmetic. Restoration or development of binocular vision can improve fusion, stereoacuity, and binocular visual field and can restore normal visual function in both eyes. This can lead to long-term stability of ocular alignment and help to reduce the number of eye surgeries required throughout a patient’s lifetime. A normal ocular alignment also enhances social interaction and eye contact, while uncorrected strabismus can adversely affect employability.3
DETECTION OF STRABISMUS
The pediatrician’s main tool in recognizing the presence of strabismus is the corneal light reflex (Hirschberg test). In normal individuals, a light shone directly or indirectly into the eyes will appear as a white reflex located centrally (or just nasal to center) in each pupil. If the eyes are misaligned, then the reflex appears at a different position relative to the pupil in the deviated eye. In esotropia (Fig. 586-1), the reflex appears more laterally in the pupil compared to the straight eye, which is fixating on the light or examiner. In exotropia (see below), the light reflex appears more nasal relative to the pupil in the deviated eye. In hyper/hypotropia, the light reflex is displaced vertically (see below).
Figure 586-1. Infantile esotropia. Note position of Hirschberg light reflex, which is more lateral relative to the pupil in both eyes. More commonly, one eye would be straight and the other largely esotropic.
PRIMARY INFANTILE ESOTROPIA
Primary infantile esotropia develops in the first few weeks to months of life, most often prior to 6 months of age. Previously, this condition had been incorrectly termed congenital esotropia. There is often a family history of strabismus, with esotropia observed in as many as 10% to 20% of first-degree relatives.4 Classic infantile esotropia is constant and involves a large amount of misalignment, often 25 to 35 degrees (40 to 60 prism diopters) at both distance and near viewing (Fig. 586-1). Infantile esotropia rarely can resolve spontaneously over time, with the magnitude of deviation being inversely proportional to the probability of resolution. Multiple studies have confirmed that a constant large esotropia that is still present at age 2 to 4 months is unlikely to resolve without treatment, and the angle of strabismus may increase with continued observation.5
Normal amounts of farsightedness are present in most of these patients. Glasses are therefore not generally required or helpful, as the esotropia is unrelated to the refractive error. Significant nearsighted or astigmatic refractive error, if present, may require correction, not to improve the alignment but to maximize vision. Managing primary infantile esotropia generally involves eye muscle surgery, which is successful approximately 80% of the time after a single operation. Surgical treatment of infantile esotropia generally involves recession (weakening) of the medial rectus muscles on both eyes. Most clinical experience suggests that very useful, sometimes near-normal sensory and oculomotor functions can be developed or restored if successful ocular alignment is achieved within the first 2 years of life.6,7 The optimum timing for eye muscle surgery for primary infantile esotropia is the subject of much research, with some suggesting intervention as young as 6 months of age in an effort to maximize binocular visual potential. Even surgery as early as 13 weeks has been advocated by some ophthalmologists.8 Botulinum toxin injection into the medial rectus has been investigated as an alternative to traditional surgery. While some authors have noted success with smaller deviations, the efficacy when compared to incisional surgery has not always been convincing.9
Careful longitudinal follow-up of these patients is necessary, since an accommodative esotropia (see below) requiring glasses can develop at a later date. Even with successful surgical ocular realignment, patients with infantile esotropia are more likely to exhibit latent nystagmus, vertical misalignment, and monocular smooth pursuit abnormalities. These features may persist throughout the patient’s life.
When we focus on objects near us, the ciliary muscle of the eye contracts, resulting in relaxation of the lens (a process called accommodation), and the eyes converge. Children have particularly large abilities to accommodate. We lose this ability in later adulthood and thus the reason for needing reading glasses or bifocals. If a child is farsighted, they need to accommodate even more than usual to focus, and they are able to do so without any sense of stress or discomfort. In fact, most children are farsighted in the first decade of life, and very few need glasses. But in some children, this excess accommodative need results in overconvergence of the eyes, called accommodative esotropia.
Children with accommodative esotropia generally present between the ages of 18 and 48 months of age, with an average age of onset of 2.5 years. The esotropia is often intermittent in the beginning and becomes constant without intervention. The amount of esotropia is generally less than is present in patients with primary infantile esotropia and may be more prominent at near fixation. These children have larger than average amounts of hyperopia, averaging about +4 diopters, with some patients exhibiting as much as +8 to 10 diopters. Over 30% of children with +4 diopters or more of hyperopia will develop esotropia by 3 years of age. Amblyopia may also develop, even bilaterally, in children whose hyperopia is excessively high. Some experts contend that children with accommodative esotropia more frequently have amblyopia at presentation than children with infantile esotropia.
Figure 586-2. Accommodative esotropia. Child has left esotropia (note abnormal Hirschberg light reflex) with glasses off (A) but straight eyes with glasses on (B).
Managing accommodative esotropia usually involves spectacle correction for the farsightedness to eliminate the need to accommodate and overconverge. Bifocals may be required if there is excessive accommodative convergence at near fixation. With the glasses on, the patient has straight eyes. When the glasses are removed, the patient again starts to accommodate in order to see clearly and the eyes are esotropic (Fig. 586-2). The child may actually see as clearly without the glasses as with them, but the glasses are there to keep the eyes straight.
A second form of accommodative esotropia does not involve farsightedness. Children with this subtype of esotropia often have straight eyes, or nearly so, when looking at an object in the distance, but their eyes cross excessively only when fixating on near objects. This is due to an abnormal relationship between accommodation and convergence. These children are most often treated with reading glasses (if correction is needed only for near work) or bifocals (if they also need correction to see clearly at a distance, such as with astigmatism).
A miotic agent such as phospholine iodide, a cholinesterase inhibitor, is sometimes effective in realigning the eyes of patients with accommodative esotropia where compliance with wearing glasses is poor but potential ocular and systemic side effects limit their long-term usage.
It is normal for children to demonstrate increasing amounts of hyperopia until 6 to 8 years of age, when the amount of hyperopia naturally begins to decrease in most children. In patients with accommodative esotropia, a gradual reduction (“weaning”) of the spectacle strength may be possible over time, while maintaining good vision and alignment. If glasses are worn faithfully and good fusional patterns are established, many patients with refractive esotropia can be weaned from their glasses by the time they are teenagers. The same is true for bifocals. When beneficial, bifocal correction can often be weakened after 4 to 7 years of age and even eventually eliminated in over half of cases, usually by the midteens. A few eye surgeons recommend eye muscle surgery for children who cannot be weaned out of bifocals by 15 to 16 years of age. This allows the patient to discontinue bifocal wear and simply wear single-vision glasses or contact lenses.
Figure 586-3. Pseudoesotropia. Note that the Hirschberg light reflex is symmetric in the pupil of both eyes. Even though the eyes look grossly esotropic, they are actually aligned.
Some patients will always need glasses (or contact lenses) to keep their eyes straight. Significant delay, as little as 3 to 4 months, in initiating spectacle treatment following the onset of accommodative esotropia increases the possibility that a portion of the esotropia will not resolve with spectacle correction alone. This mixed form of strabismus (partially accommodative esotropia) often requires surgery for the nonaccommodative component.
BASIC ACQUIRED ESOTROPIA
Esotropia that develops after infancy and is not accommodative is termed basic acquired esotropia. Organic pathologies, often in the retina or vitreous of the eye (eg, traumatic injury, cataract, Toxoplasmainfection), have been diagnosed in a significant percentage of these patients, emphasizing the importance of an ophthalmologist performing a complete eye examination (with pupil dilation) in any patient presenting with strabismus. Underlying central nervous system lesions in otherwise healthy children must also be considered and ruled out by neuroimaging or pediatric neurological consultation if no ocular pathology is found. Underlying refractive error or amblyopia should also be treated in an appropriate manner.
After ruling out other specific ocular or neurological pathology, management of acquired esotropia generally requires strabismus surgery. This usually involves bilateral medical rectus recession (weakening) or unilateral surgery with medial rectus recession and lateral rectus resection (strengthening).
The infant often has a wide, flat nasal bridge with prominent epicanthal folds. The child may appear esotropic even when the eyes are straight, because there is less white sclera visible medially compared to laterally, especially if the child is looking slightly to one side or looking up close. This optical illusion causes the child to appear cross-eyed (Fig. 586-3). The Hirschberg light reflex test is normal. While no treatment is necessary for pseudoesotropia, as this appearance will disappear spontaneously as the infant grows older, these children should be reevaluated every 6 to 12 months, since some of these patients may develop accommodative or acquired esotropia at a later age.
Intermittent exotropia is the most common exodeviation. The onset of intermittent exotropia usually occurs before 5 years of age, but it may go undiagnosed until much later, even into adulthood. Fusional mechanisms (the natural neural drive to use both eyes together and simultaneously) are present to intermittently control the exodeviation. Initially the eyes deviate only in times of fatigue, visual inattention, or illness, when these mechanisms are reduced. Most patients with intermittent exotropia have normal visual acuity or, rarely, mild amblyopia. Intermittent diplopia may rarely be a complaint. Children with intermittent exotropia will often squint or close one eye in bright sunlight for reasons that are not well understood. The deviation is generally larger for distance viewing and initially is often not present or greatly reduced with near fixation. The natural history of untreated intermittent exotropia is unclear. Some reports suggest that the exotropia will remain stable or will improve, while most experienced clinicians have found that the majority of patients will deteriorate with long-term follow-up. If the exotropia becomes constant, binocular vision and stereopsis will deteriorate or be lost.
Figure 586-4. Right eye exotropia. Note position of Hirschberg light reflex, which is more nasal relative to the pupil in the exotropic eye.
The management of intermittent exotropia can involve both nonsurgical and surgical modalities. Corrective spectacles for any clinically significant refractive error, especially myopia or myopic astigmatism, can improve the fusional control of intermittent exotropia, presumably on the basis of improved vision allowing both eyes to be used together more efficiently. Adjusting the glasses prescription to stimulate accommodative convergence can improve control of the strabismus in patients with intermittent exotropia. Part-time patching of the dominant (nondeviating) eye 4 to 6 hours per day, or alternate patching when no obvious dominant eye is detected, can also be very effective. Patching is rarely curative, and fusional control often deteriorates when patching is discontinued. Intermittent exotropia is one of the few strabismus conditions that may actually benefit from active “vision therapy” or orthoptic treatment, particularly when the exotropia is more prominent at near viewing (convergence insufficiency, see below).
Extraocular muscle surgery is generally considered when an exodeviation occurs frequently or when the amount of deviation is large enough to result in reduced binocularity or poor appearance and has not responded to more conservative management with part-time patching, spectacles, or eye exercises. Timing of strabismus surgery in patients with intermittent exotropia is also controversial. Surgical realignment before 7 years of age, before the duration of exodeviation has reached 5 years, or while the deviation is still intermittent appears to increase the probability of success.10
Onset of constant exotropia during early infancy is very unusual and should raise the question of other ocular or central nervous system abnormalities that may require further investigation. There is an increased incidence of constant exotropia in children with perinatal or neurological risk factors, such as prematurity, genetic disorders, and intrauterine drug exposure.11 More commonly, constant exotropia is diagnosed in older patients (Fig. 586-4) who have a history consistent with a decompensated intermittent exotropia or with a sensory exotropia caused by any ocular condition that reduces the visual acuity in one eye. While infants and young children who lose vision in one eye are equally likely to drift in or out, older children and adults are more likely to develop exotropia.
Managing constant exotropia with the non-surgical modalities described in the “Intermittent Exotropia” section is generally unsuccessful and therefore not initiated. Surgical treatment is generally required and usually involves bilateral lateral rectus muscle recessions or a lateral rectus recession and medial rectus resection on the nondominant eye. Patients and their families must be warned that postoperative diplopia immediately after surgery is common in these patients but generally resolves spontaneously or with orthoptic exercises.
Patients with convergence insufficiency generally complain of “eye strain,” blurred near vision, or reading problems (asthenopia). These patients often have an exophoria at near and develop intermittent exotropia with prolonged or strong near effort. Patients with convergence insufficiency are good candidates for orthoptic therapy. “Pencil push-ups” (holding a pencil out at arm’s length, the patient focuses on the writing on the pencil and then slowly brings the pencil to near viewing while keeping the pencil in focus) and other near-point exercises are generally employed. Glasses with prisms in the lenses can also be beneficial to stimulate fusional convergence. In addition, computer-based orthoptic exercises are available commercially at a nominal cost. Eye muscle surgery may be required if nonsurgical treatment is ineffective or if compliance is poor.
In patients with pseudoexotropia, the eyes appear to be turned outward when they are actually straight. It occurs in association with widely spaced eyes or retinal variations, especially following retinopathy of prematurity. The Hirschberg light reflex test will be normal. Children with pseudoexotropia should still be examined periodically during childhood, since true exotropia may develop.
DISSOCIATED VERTICAL DEVIATION
Dissociated vertical deviation (DVD) is a common disorder seen frequently in isolation or in patients with infantile esotropia or exotropia. The etiology is unknown. With inattention or occlusion, each eye may slowly drift upward and outward (Fig. 586-5). Initially the hyperdeviation is latent but may become constant and continuously visible over time, resulting in the need for surgical treatment.
Figure 586-5. Dissociated vertical deviation. The patient’s right eye looks straight until it is covered (A), after which it drifts upward and stays in that position when the cover is removed (B). Note position of Hirschberg light reflex, which is lower relative to the pupil in the upgoing (hypertropic) eye.
NONCOMITANT VERTICAL DEVIATIONS
Overaction of the oblique muscles, both inferior oblique or superior oblique muscles, generally results in vertical strabismus that is variable and generally greatest in adduction, where the oblique muscles have the greatest action. The affected eye will either be hypertropic (inferior oblique overaction) or hypotropic (superior oblique overaction) in adduction (contralateral gaze). Oblique overactions can also result in horizontal incomitance in up or down gazes, called A-Pattern (eyes farther apart in down gaze and closer in up gaze) or V-Pattern (eyes farther apart in up gaze and closer in down gaze). Patients may keep their chin up so that their eyes are most aligned when looking straight ahead. Management of oblique muscle overaction, if significant or symptomatic, requires eye muscle surgery.
CRANIAL NERVE PALSIES
CRANIAL NERVE IV (CN IV) PALSY
The trochlear nerve (cranial nerve IV) innervates the superior oblique muscle. This palsy may be congenital or may result from head trauma or intracranial tumors. The long intracranial course of the nerve makes it uniquely susceptible to injury. The palsy may be unilateral or bilateral. Most commonly, affected patients will have a hypertropia of the involved eye and a head tilt to the opposite side. When the defect is congenital, the spontaneous head tilt can be mistaken for a sternocleidomastoid muscle problem, and the patient may be referred to an orthopedist or physical therapy. If the head tilt improves when one eye is covered, the nature of the problem is ocular, most likely a superior oblique palsy. Children with congenital superior oblique palsy also often develop a characteristic facial asymmetry, with mild hemifacial microsomia on the dependent (lower) side of the face and a curving of the nose toward the affected side, which can be diagnostic.12
Patients with small vertical deviations can sometimes be managed with prisms in the lenses of their spectacles. This method is most applicable when patients already require spectacles to see clearly. Most cases of acquired CN IV palsy should be observed for spontaneous improvement for at least 6 months.13 At that time, if the patient is symptomatic and the deviation is not controlled with a head tilt or prisms, eye muscle surgery is indicated.
CRANIAL NERVE VI PALSY
Cranial nerve VI (abducens nerve) innervates the lateral rectus muscle, which abducts the eye. Transient, benign, unilateral abducens palsy is rarely seen in the newborn period and resolves over 2 to 3 months. Spontaneous abducens palsy (often called benign postviral VI palsy) may also occur in childhood, often after viral illness. Acquired abducens palsy is most commonly seen after closed head injury or in association with increased intracranial pressure. A significant number of cases are associated with intracranial lesions and may have associated neurological manifestations. Abducens palsy is characterized by esotropia in primary gaze that increases in ipsilateral side gaze. Limited abduction, diplopia, and a head turn toward the side of the paresis are also often seen.
When there is not a clear history of trauma, a careful history should be taken to define antecedent infections or immunizations. Neuroim-aging should be considered whenever other neurological signs or symptoms are present. Depending on the child’s age, patching may be required in younger children to prevent the development of amblyopia. Fresnel press-on prisms can be applied to spectacles to eliminate diplopia in primary position, improve anomalous head postures, and prevent amblyopia. Spontaneous resolution can be expected in the majority of acquired idiopathic, postviral, and posttraumatic VI palsies. Therefore, observation for at least 6 months prior to surgical intervention is generally recommended. Some surgeons may inject botulinum toxin into the ipsilateral medial rectus muscle to reduce symptomatic diplopia and prevent contracture of the medical rectus while awaiting spontaneous recovery of abduction. Surgery is indicated when spontaneous resolution does not take place and after exclusion or treatment of intracranial pathology.14
Duane retraction syndrome (DRS) can mimic a cranial VI palsy but has a much more benign implication. It has been described with a spectrum of motility abnormalities, including limited abduction, adduction, and both abduction and adduction, resulting in esotropia, orthotropia, or exotropia in primary gaze. The common denominator is globe retraction in attempted adduction. DRS type 1, with deficient abduction, is the most common form and most confused with cranial VI palsy (Fig. 586-6). Careful observation for globe retraction on adduction, best viewed from the side of the patient, and narrowing of the palpebral fissure (Fig. 586-6) can save the patient a neurological workup for cranial VI palsy. The motility problem is congenital (but often not noticed for years due to compensation by the child by turning the head to look to the affected side), usually unilateral (but may be bilateral in up to 10% of cases), more frequently seen in girls, most often present on the left side, and usually sporadic.
Most DRS patients have some position of gaze in which the eyes are aligned so that the majority develop very good binocular vision and avoid amblyopia. While most DRS patients have the ocular motility disturbance as an isolated finding, DRS has been associated with systemic syndromes such as Goldenhar syndrome. The etiology of the motility disorder in most patients appears to be a congenital absence of the cranial VI nucleus in the brain stem. There is also anomalous innervation of the affected lateral rectus muscle by a branch of cranial nerve III that results in cocontraction of the medial and lateral rectus muscles on adduction, producing the globe retraction. Surgery is indicated in DRS patients who have significant strabismus in primary position and for those who assume a significant abnormal head position, most commonly a face turn.
CRANIAL NERVE III PALSY
Paresis of the cranial nerve III (oculomotor nerve) is fortunately infrequent in childhood, but when present, it can be devastating to the visual system and visual development. This is because four of the six extraocular muscles, the levator palpebrae, and muscles of accommodation are all innervated by this nerve. Nearly half of pediatric cranial nerve III palsies are congenital. Acquired oculomotor palsies can result from trauma; serious infection; and, less commonly, tumor. Characteristics of this palsy include unilateral ptosis, anisocoria (unequal pupils), and strabismus. The child’s affected eye is “down and out,” exotropic and hypotropic, from unopposed action of the superior oblique muscle and lateral rectus muscle.
Figure 586-6. Duane retraction syndrome type 1. Note the deficiency of abduction of the left eye, which would mimic a cranial VI palsy. In adduction, the left eye has narrowing of the palpebral fissure. This narrowing in adduction of an eye that cannot abduct differentiates Duane syndrome from cranial VI palsy.
Management of children with oculomotor nerve palsy is very difficult. Amblyopia is usually present and difficult to treat. Patients who do not recover from the palsy after 6 to 12 months may be considered for eye muscle surgery.15 In most cases of severe cranial III palsy, the best achievable outcome is alignment of the eyes and possibly single binocular vision in primary position. Ptosis surgery is also often required.
BROWN (SUPERIOR OBLIQUE TENDON SHEATH) SYNDROME
Brown syndrome is the limited elevation of the affected eye in adduction.16 This syndrome most commonly presents in a congenital form but can occur secondary to trauma or inflammatory conditions in the area of the trochlea.17Restriction of free passage of the superior oblique tendon through the trochlea is common to all forms of Brown syndrome. Observation alone without intervention remains the most common management for all presentations of Brown syndrome since the strabismus (hypotropia) is usually present only in up gaze in the adducted position. Intervention is indicated when there is a significant hypotropia in primary position or when the child has to assume an abnormal chin-up or face-turn head position to maintain binocular vision. For post-traumatic and inflammatory-associated Brown syndrome, oral anti-inflammatory agents or local steroid injection can help selected patients improve.
DOUBLE ELEVATOR PALSY (MONOCULAR ELEVATION DEFICIENCY SYNDROME)
Double elevator palsy is a congenital condition associated with hypotropia and sometimes ipsi-lateral ptosis associated with an inability to look upward with the affected eye. The etiology of this condition is unclear but must be differentiated from a central nervous system cause involving the superior colliculus such as increased intracranial pressure or tumor. Surgical intervention is indicated if a significant hypotropia exists in primary position or if the child assumes a large chin-up posture in order to fuse.
CONGENITAL CRANIAL DYSINNERVATION DISORDERS (CCDD)
This family of disorders result in strabismus, almost always incomitant, due to congenital abnormalities of muscle innervation. Duane syndrome and Brown syndrome (see above) may be included. The prototype disorder is congenital fibrosis of the extraocular muscles (CFEOM), a rare genetic entity characterized by secondary fibrosis of individual extraocular muscles, usually bilaterally, with various amounts of restriction of eye movement into the opposite field of gaze. The spectrum ranges from isolated fibrosis of a single muscle to bilateral involvement of all the extraocular muscles. Patients have reduced eye movements and anomalous head positions. Surgical management is very difficult and requires the operative release of the restricted muscles. Restoration of ocular motility is not possible. An optimal result can merely mean straight eyes with little movement in primary position.18
Other disorders classified as CCDD include horizontal gaze palsy with progressive scoliosis (HGPPS) and Moebius syndrome.