Nonparalytic horizontal strabismus

Omar Solyman MD

Neuro-Ophthalmology & Neuro-Otology

Updated 02.15.2024
Released 12.12.2002
Expires For CME 02.15.2027

Nonparalytic horizontal strabismus

Author: Omar Solyman MD

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Editor: Heather E Moss MD PhD

Nonparalytic horizontal strabismus

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Introduction

Overview

The author reviews the different forms of nonparalytic horizontal strabismus (eye misalignment), including eyes in-turning (esotropia) and out-turning (exotropia) strabismus. This is the most common kind of strabismus with comitant (similar magnitude of ocular misalignment in all directions of gaze) heterotropia, representing 67% to 74% or significant/decompensated heterophorias 8% to 17%, according to two epidemiologic studies (50). These are distinguished from paralytic strabismus, which may result from extraocular muscle paresis or under action from neurologic deficit at any point along the extraocular motor pathway from the cerebral cortex, through brain stem, along the oculomotor nerves (III, IV, and VI), and the neuromuscular junction to the extraocular muscles. Paralytic strabismus is usually incomitant, with a higher magnitude of deviation (more pronounced misalignment) in the field of action of the paretic muscle, and represents 7% to 10% of all strabismus cases (50).

Treatment of nonparalytic strabismus conditions includes nonsurgical measures like patching one eye or glasses. In some cases, strabismus surgery is helpful to restore binocular vision, to correct abnormal head posture, and for psychosocial reasons. Nonparalytic strabismus conditions may have different pathophysiologic mechanisms, some of which are yet to be discovered.

Although nonparalytic eye deviations are usually isolated ocular conditions, they rarely may have an underlying neurologic disease or are part of a systemic syndrome and may require neurologic work-up. Also, mild paralytic strabismus may be subtle and masquerade as nonparalytic comitant strabismus on cursory examination. The aim of this update is to review different types of nonparalytic strabismus and how to differentiate them from subtle paralytic mimickers.

Key points

	• Horizontal strabismus (eyes misalignment) can be classified by exotropia (turned out) and esotropia (turned in).
	• Nonparalytic strabismus refers to ocular misalignment and is not due to cranial nerve or neuromuscular junction causes.
	• Treatment of nonparalytic strabismus conditions includes nonsurgical measures like patching one eye or glasses as well as surgery to establish or restore binocular vision, to correct abnormal head posture, and for psychosocial reasons.
	• Nonparalytic strabismus may rarely be secondary to an underlying neurologic cause and may require neurologic work-up.
	• Mild paralytic strabismus may masquerade as a comitant nonparalytic strabismus on cursory examination.
	• Nonparalytic strabismus can present as an association of a general condition of neurologic importance, such as cerebral palsy, craniosynostosis, and traumatic brain injury, with particular considerations in diagnosis and management.

Historical note and terminology

In primitive folklore and mythology, strabismus, which is misalignment of eyes relative to each other, was considered an affliction sent by a malignant spirit or evil god. The bad luck brought from the look of cross-eyed person forms the basis for the legends based on “the evil eye." Maya, the Egyptian goddess, squinted; and the statue of King Djoser (2600 BC), for whom the first pyramid was erected, depicts him as having a large internal ocular deviation. Hippocrates first differentiated between paralytic and nonparalytic type of squint and correctly stressed the hereditary aspect of the latter.

Ocular deviations are described as a phoria or a tropia (used as a suffix). A phoria is a misalignment of the visual axis kept in check by fusion, meaning that when both eyes are being used the eyes are aligned, but the misalignment occurs when vision in one is interrupted. Fusion is an innate drive to keep each fovea directed to the object of regard, thus, allowing single binocular vision and stereopsis (depth perception). A tropia is a manifest misalignment of the visual axis not controlled by fusion, meaning that when both eyes are being used the misalignment is evident.

Terminology of ocular misalignment:

	• Eso: a prefix that means inward “toward the nose” deviation
	• Exo: a prefix that means outward “away from the nose or toward the ear” deviation
	• Hyper: a prefix that means upward deviation
	• Hypo: a prefix that means downward deviation
	• Hetero: a prefix that means deviation
	• Ortho: a prefix that means straight
	• Apparent or pseudo-strabismus (apparent esotropia or exotropia): straight eyes that give false impression of apparent inward or outward strabismus or pseudo-esotropia or pseudo-exotropia, respectively.
	• Prism diopter: Prism diopter is the measurement unit of ocular misalignment with larger numbers meaning larger deviation. One prism diopter deviates the light reflex 1 cm at 1 meter.

Measurement methods of strabismus convenient for bedside examination by neurologists include the following:

	• Hirschberg test or corneal light reflex test: The Hirschberg test gives an approximate estimate of the angle of ocular misalignment by observing the displacement of the corneal light reflex from the center of the cornea. Each 1 mm of displacement requires approximately 15 PD to correct. So, a displacement of 3 mm (midway between the center of the pupil and the limbus) indicates approximately 45 PD, and a displacement of 4 mm indicates approximately 60 PD.
	• Krimsky light reflex: The Krimsky light reflex is useful in uncooperative patients (eg, in children) and in patients with a single seeing eye. It measures the misalignment by centering the corneal light reflex of both eyes using an appropriate prism in front of the one seeing eye, without the need for alteration of fixation between both eyes.
	• Cover test: This test involves covering one eye at a time while the patient fixates and watching the other eye for refixation movement, which would indicate tropia. The alternate cover test is the most commonly used and most accurate method of measurement, where a patient fixes on a target, and the eyes are alternately covered. Any saccade of an eye after being uncovered suggests that the eye has deviated in the opposite direction when covered. The alternate cover test should ideally be done in the nine cardinal directions of gaze, with the patient fixing on a distant target at 20 feet. It should also be performed at near, with the patient fixing on a target at 33 cm. The deviation can be quantified in prism diopters.
	• Maddox rod: Maddox rod is a technique for separating and quantifying horizontal and vertical strabismus when associated with double vision and requires specialized equipment and the patient’s cooperation.

Clinical manifestations

Presentation and course

Esodeviations

Nonparalytic inward (toward the nose) eye deviations are classified into congenital and acquired esotropia. Congenital (also known as infantile or early onset) is the most common ocular misalignment in children under 6 months of age. Esotropia developing after 6 months of age is considered acquired and may be subclassified into accommodative, partially accommodative, and nonaccommodative. Nonaccommodative acquired esotropia includes acute onset esotropia, sensory esotropia (resulting from poor vision in one eye), and consecutive esotropia after a previous surgery to correct exotropia. Other causes of esotropia include convergence excess, convergence spasm, divergence insufficiency, sagging eye syndrome, heavy eye syndrome, and acquired distance esotropia in myopic patients.

Congenital or infantile esotropia. The terms "congenital” and “infantile” esotropia are used interchangeably to describe an esotropia of large angle, developing prior to 6 months of age. Infantile esotropia may be the more accurate term.

Infantile esotropia does occur in families (10). Children born with a neurologic deficit such as cerebral palsy, hydrocephalus, and neonatal or postnatal seizures, as well as prematurity, have a higher frequency of infantile esotropia. Infantile esotropia may be associated with other ocular motor abnormalities that include inferior oblique overaction, dissociated vertical deviation, and latent nystagmus.

Inferior oblique overaction. Inferior oblique muscle overaction manifests as excessive elevation of the eye in adduction and is reported in up to 70% of patients with esotropia, usually appearing after the age of 2 to 3 years. Unlike an inferior oblique muscle overaction noted in cases of true superior oblique (fourth nerve) palsy, there is no vertical deviation in primary position (ie, when looking straight ahead) in patients with primary inferior oblique overaction (40).

Dissociated vertical deviation. Dissociated vertical deviation is an ocular motor abnormality that may occur in isolation or more commonly as part of the infantile esotropia syndrome. Dissociated vertical deviation most often occurs in the context of preexistent infantile strabismus, typically infantile esotropia (may affect up to 90% of cases of infantile esotropia), but it may also occur in the context of other conditions with intense disturbance of binocular vision, such as other childhood misalignments, eg, presumed infantile microstrabismus and exotropia and in association with acquired loss of vision in childhood. The common feature of all these scenarios associated with dissociated vertical deviation is “intense disturbance of binocular vision” early in childhood. This spontaneous deviation occurs when the patient is tired, distracted, or when fusion is interrupted by covering one eye. It consists of a triad of elevation, abduction, and excyclotorsion of the eye (rotation of the globe about an anteroposterior axis with the 12 o’clock point moving outward or toward the ear). It may be unilateral or bilateral. These deviations are notoriously difficult to measure by cover testing as the deviation continues to increase as more and more vertical prisms are added; therefore, the deviation builds on cover testing. The confirming clinical sign of a dissociated vertical deviation is that as the uncovered, deviated eye shifts downwards to take up the fixation, the eye fixing earlier does not show a corresponding downward shift, thus, violating the Herring law, as there is no accompanying hypotropia (downward deviation) of the opposite eye. Large, frequently apparent dissociated vertical deviations require surgical correction (18).

Latent nystagmus. Latent nystagmus frequently is not present under binocular viewing conditions and manifests only with occlusion of one eye, as a jerk nystagmus that develops in both eyes with the fast phase towards the viewing eye (41).

Cross fixation is often noted in infantile esotropia with large angle of deviation and manifests as using the left eye to look to the right side and the right eye to look at the left side, without moving the eyes out. This often results in an apparent under action of the lateral rectus, giving the appearance of bilateral sixth nerve palsy. Evaluation of abductions after occluding one eye or alternatively by dolls-head maneuver (“spinning the child while in an upright position”) can differentiate both conditions. If these techniques fail, patching one eye for several hours may help show the full range of abduction (28).

Infantile esotropia requires surgical correction of the misalignment before the age of 2 years. Younger age at first surgery (before 10 months) may be associated with a higher rate of binocularity and stereopsis; however, rarely do these children obtain excellent stereo acuity. Several preoperative factors, such as larger preoperative angle of deviation, lateral rectus under action, and presence of amblyopia, have been reported to be associated with higher rates of horizontal reoperation. Early surgery, which is preferred for better binocular function, has been associated with a higher risk of reoperation as well. Botulinum toxin chemodenervation of the medial rectus muscle has been described as a substitute for or an adjunct to surgery (26). A good result is considered when a condition called monofixation syndrome is established, which consists of a small angle esotropia less than 8 prisms, with mild amblyopia, peripheral fusion, and some stereopsis (22; 54).

Accommodative esotropia. Accommodative esotropia frequently presents at about the age of 2.5 years with a range of 6 months to 6 years. Classically, the parents describe an intermittent esotropia of variable amount most notable when the child is tired, upset, or fixing on a near target. A family history of a similar type of turn may be found in first degree relatives in about 25% of patients (58; 04). The diagnosis and correct treatment of an accommodative esotropia is an urgent pediatric ophthalmology problem as these children, if left untreated for several weeks to months, will develop an amblyopia and a possible permanent loss of stereopsis and sensory fusion. Cycloplegic refraction reveals a moderate (+2.50) or greater amount of hyperopia that when corrected, results in good alignment at near and far distances with the use of glasses. If corrected early these children are not only spared amblyopia but maintain excellent stereopsis (14; 30).

Parents are frequently disappointed to learn that glasses rather than surgery are the mode of treatment for this entity. The disappointment arises from two concerns: (1) esthetic, that is, their child has to wear glasses, and (2) the fact that when the glasses are removed the deviation persists. It’s important to empathize full-time glasses wear and regular follow up to prevent amblyopia. It may be reassuring to mention to caregivers that although the course of their child cannot be predicted, some children can be weaned of their glasses over several years and maintain straight eyes. For those who require glasses through their adulthood, refractive surgery can be a viable option when their refraction stabilizes to achieve straight eyes without glasses.

A subcategory of accommodative esotropia is those children where the glasses correct the deviation at distance but there remains a large deviation when the patient fixes at a near target. These patients have an abnormal convergence response to an accommodative stimulus, a high accommodative convergence to accommodation ratio. This group requires the use of bifocal glasses to maintain alignment on a near target. A portion of these children will eventually be able to discontinue the use of bifocals as they reach 6 to 8 years of age but may continue to require hyperopic spectacles to maintain proper ocular alignment throughout life.

Some children with accommodative esotropia, with or without a high accommodative convergence to accommodation ratio, will deteriorate and come to a point where glasses alone will no longer suffice to maintain good ocular alignment. These patients, termed "partially accommodative esotropes" will require both surgery and glasses to keep their eyes straight. Often, they will have responded well to glasses alone maintaining excellent alignment with their glasses, but after a few years they develop an intermittent deviation, which is no longer corrected with glasses. They require surgical correction of the residual deviation, and parents must be warned that glasses will still be required postoperatively.

Acute-onset esotropia. The most vexing type of childhood strabismus is the acquired nonaccommodative esotropia, which appears at about the age of 3 or 4 years. This may occur suddenly (usually with diplopia) and may at first be intermittent or constant. Careful history taking with an emphasis on review of symptoms questioning about complaints of headaches, loss of balance, and minor trauma is of great importance as posterior fossa tumors have rarely been reported in association with acute comitant esotropias in children (16). However, the large majority of these children are otherwise well, though those of recent onset with diplopia will complain of their double image or blurred vision. Careful assessment of ocular motility to rule out subtle lateral rectus palsy is of utmost importance. Cycloplegic refraction to rule out an accommodative component is compulsory. Close observation and subsequent strabismus surgery are required. If undertaken early, these patients have a good prognosis for restoration of binocular vision (29).

Convergence spasm. Also known as spasm of the near reflex, convergence spasm is a common cause of acquired esotropia, which is usually a functional disorder triggered by prolonged near work and stress and presents with blurry vision, periocular pain, and headache. Convergence spasm may be misdiagnosed as sixth nerve palsy; however, the first is always accompanied by near triad features of miosis and acquired nearsightedness (pseudo-myopia) that, in addition to full monocular abductions, normal vestibulo-ocular reflex and optokinetic response help to differentiate it from the latter. Although convergence spasm most commonly has a functional etiology, it is rarely caused by lesions in midbrain or thalamus and has been reported with multiple sclerosis, NMO-spectrum disorder, peripheral vestibulopathy, thalamic hemorrhage, posterior fossa tumor, and Arnold-Chiari malformation (23).

Treatment options for isolated idiopathic or functional convergence spasm include long-acting cycloplegic drops, occlusion of the medial portion of spectacles, psychiatric consultation, and rarely, the use of prism glasses (06).

Divergence insufficiency. Divergence insufficiency presents as a comitant esotropia and diplopia, which is greater at distance than at near and is most commonly an isolated condition caused by involutional orbital changes mainly in the lateral rectus-superior rectus band degeneration in elderly people. Divergence insufficiency may be mimicked by subtle bilateral sixth nerve palsies; however, convergence insufficiency usually has gradual onset and slow progression, in contrary to sixth nerve palsy that usually has a sudden onset. Slowed abducting saccades and possibly papilledema from elevated intracranial pressure in cases of bilateral sixth nerve palsy help in the distinction.

Esotropia greater at distance may also be a feature of other neurologic disorders like cerebellar diseases, including spinocerebellar degeneration and Chiari malformation. Careful attention to symptoms and signs of cerebellopathy is paramount in suspicious cases. Divergence insufficiency secondary to neurologic disease is much higher in children. Treatment of isolated divergence insufficiency include prisms or eye muscle surgery (06).

Sensory esotropia. Sensory esotropia results from poor central vision in one eye in very young children. Older children and adults with unilateral poor vision tend to develop sensory exotropia, instead. Sensory esotropia may result from severe optic nerve or retinal disease or from ocular media opacity (eg, congenital cataract) and should be urgently worked up for possible treatable disorders. Sensory esotropia may be the first presenting feature of retinoblastoma, a life-threatening malignancy of the retina in infants. Full eye assessment, including a dilated fundus examination, is required for children presenting with esotropia.

Cyclic esotropia. This is a very rare type of esotropia that appears and disappears in a periodic cyclic pattern, usually in a 48- to 72-hour cycle. On squinting days, the esotropia is large and associated with suppression and no diplopia. On nonsquinting days, no deviation or only a small phoria is identified, and fusion is present. Abnormal electroencephalogram, behavioral changes, and excessive sleepiness have been reported in some patients on squinting days (49).

Heavy eye syndrome. Heavy eye syndrome, also known as myopic strabismus fixus or convergent strabismus fixus, was first coined by Bagshaw in 1966 in a report of two cases that were attributed to a presumed heavy ocular globe secondary to high myopia (03). Heavy eye syndrome is an acquired, progressive strabismus typically seen in eyes with increased axial lengths and high myopia, typically more than 25 diopters, and presents with a progressive, usually large angle esotropia and hypotropia with limited abduction and supraduction. There are some case reports of convergent strabismus fixus in the absence of high myopia and strabismus fixus in the setting of exotropia; however, these cases are rare and more controversial.

Several theories have tried to explain the pathophysiology of heavy eye syndrome. The most plausible theory postulates that the superotemporal quadrant of the posterior globe prolapses out of the muscle cone secondary to myopic globe elongation. This causes the elongated globe to herniate between the superior rectus and lateral rectus muscles, thereby displacing the superior rectus medially and the lateral rectus inferiorly, which increases the force of adduction and leads to limited supraduction and abduction, respectively. Patients with heavy eye syndrome typically present with diplopia secondary to progressive esotropia and hypotropia, with limitation of abduction and supraduction. Patients can also have pseudoptosis in the setting of hypotropia and pseudoproptosis in the setting of high myopia, with an elongated globe and a head tilt to the side of the hypotropic eye to achieve single vision or a chin-up posture to compensate for the hypotropia. Heavy eye syndrome should be differentiated from sagging eye syndrome and from abducens palsy. Differentiating heavy eye syndrome from abducens palsy relies on investigating timing and acuteness of onset, any underlying patient risk factors (ie, hypertension, hyperlipidemia, cardiovascular disease), refraction, and if the deviation is concomitant or inconcomitant as an inconcomitant deviation makes a cranial nerve VI palsy more likely. A high-resolution orbital MRI shows severe superotemporal globe prolapse that displaces the lateral rectus pulley inferiorly and the superior rectus muscle medially (33; 20).

Sagging eye syndrome. Sagging eye syndrome was coined by Rutar and Demer in 2009 to describe strabismus with possible secondary to age-related degeneration of the collagenous extraocular muscle pulley system, resulting in downward “sagging” of lateral rectus pulley. Associated with downward sagging of the lateral rectus pulley, the superior rectus–lateral rectus fibrous band enlarges, ruptures, and eventually disappears on further progression. If the lateral rectus pulley and the superior rectus–lateral rectus fibrous band change symmetrically, distance esotropia occurs. If change is asymmetric, hypertropia develops. Characteristic facial features in patients with sagging eye syndrome resulting from ocular adnexal changes include baggy eyelids, deep superior lid sulcus deformity, and aponeurotic ptosis. Such features may not be noticeable if the patient has undergone rejuvenation procedures and need to be asked about specifically. Orbital MRI is helpful in the diagnosis of sagging eye syndrome, but unlike conventional orbital MRI, which includes fat suppression, fat suppression should be avoided here to allow for better evaluation of the muscle bellies. Treatment options include prism glasses or surgery.

Acquired distance esotropia in myopic patients. Acquired distance esotropia in myopic patients is an unusual, acquired, and slowly progressive esotropia that is greater at distance than at near. It occurs in young adults with myopia, and its pathogenesis is still unknown, but it may be related to long periods of near work (57).

Nystagmus blockage syndrome. Nystagmus blockage syndrome is a form of infantile esotropia associated with nystagmus on abduction of either eye, apparently limited abduction, abnormal head posture (face turn towards the side of the dominant eye), and frequent amblyopia. The differential diagnosis includes abducens palsy and crossed fixation. The treatment options include patching and surgery, but the results of surgery are less predictable than with ordinary types of esotropia (52).

Exodeviations

These may be classified according to fusion status as an exophoria, an intermittent exotropia, or a constant exotropia. Exotropia may be further divided according to distant near relationship. A deviation is considered basic if the out-turning measures the same at distance and when fixing at a near target. Divergence excess deviation refers to a larger deviation at distance than at near. A convergence insufficiency deviation measures greater on a near target than at distance.

Infantile exotropia. This is an out-turned eye developing during the first 6 months of life. The deviation is usually of large amplitude but may be intermittent. Infantile exotropia is a rarer entity than infantile esotropia. In contrast to infantile exotropia, infantile exotropia is usually associated with congenital neurologic abnormality (31; 53). There is no consensus on timing of surgery of infantile exotropia. Management of the accompanying amblyopia followed by early surgery and alignment within 24 months of onset of the misalignment may offer the best hope of obtaining a good long-term surgical outcome (56).

Intermittent exotropia. This is the most common type of out-turned eye. Age of onset is quite variable starting anywhere from age one to early teens. The deviation at first is present when the child is fatigued, ill or lacking concentration and may be only fleeting.

Parents may report that the child frequently closes one eye when in sunlight. Unlike other types of heterotropia, patients with intermittent exotropia tend to retain good vision in both eyes and stereopsis (43). In very young patients, surgical intervention should be met with some trepidation because a small esotropic overcorrection can result in a permanent loss of stereoacuity, and studies have shown that the natural history of intermittent exotropia is such that a loss of stereoacuity is quite rare (21). The optimal time to operate on these cases is debated, but surgery is generally indicated if there is a reduction in or loss of stereoacuity (at near or distance), deteriorating fusional control, a large angle of deviation, or a combination; however, potential thresholds remain poorly defined (27).

Nonsurgical treatment options are of limited long-term efficacy and include part-time alternate eye patching and prism glasses and orthoptic exercises by a certified orthoptist (08). Overminus glasses can help to control intermittent exotropia by inducing convergence along with accommodation. The first large-scale, randomized clinical trial assessing overminus spectacle therapy for the treatment of intermittent exotropia was conducted by the Pediatric Eye Disease Investigator Group. Although better control of distance exotropia was noted for the overminus group, this effect was short-lived after discontinuation of the overminus glasses. More importantly, treatment with overminus glasses was associated with an increased myopic shift that led to early discontinuation of the overminus lens therapy arm of the study (02; 07; 12).

Constant exotropia. In older patients, constant exotropia is often the consequence of a neglected intermittent exotropia, sensory exotropia (a poor seeing eye), or secondary exotropia in patients with prior strabismus surgery, usually for an esotropia. Poor vision in the deviated eye is frequently seen in constant exotropia.

Consecutive exotropia. This is a deviation that spontaneously replaces an esotropia. Often the esotropia is accommodative, and significant hyperopia as well as amblyopia is found. Treatment is surgical.

Sensory exotropia. Sensory exotropia results from poor central vision in one eye, usually in older children and adults (eg, in patients with acquired optic neuropathy).

Convergence insufficiency. Convergence insufficiency is a common condition that affects mainly adolescent and elderly age groups and presents with binocular horizontal diplopia or binocular blur at near (mainly with reading) and is usually associated with by eyestrain. Examination shows exotropia at near greater than 10 prism diopters or about 5 prism diopters greater exophoria at near compared to distance, decreased convergence fusional amplitude (to less than 15 prism diopters), and an increased near point of convergence (the closest distance of binocular fixation without binocular double vision or outward drift of one eye). Convergence insufficiency is usually an isolated process; however, it has been shown to be more prevalent in patients with parkinsonian disorders and patients with traumatic brain injury (25; 51). Treatment of convergence insufficiency include home exercises (most commonly “pencil pushups”), home computer-based therapy, and office-based therapy. Base in prisms for near work or surgical correction can be used for symptomatic unresponsive cases if all other measures fail (06).

Prognosis and complications

Amblyopia and loss of binocularity are the most common complications of strabismus, particularly with onset in childhood. Neck pain from head postures adopted to improve vision and psychosocial concerns related to appearance are other considerations in treatment planning.

Clinical vignette

An otherwise healthy 7-month-old infant is referred by his pediatrician for evaluation of suspected bilateral sixth nerve palsy. Examination shows large angle esotropia with limited abduction of both eyes. His neuro-ophthalmic exam is otherwise normal. Patching one eye at a time showed better abduction in both eyes. Rotating the child showed normal vestibulo-ocular reflex with full abduction in both eyes. Cross fixation in the setting of large angle infantile esotropia is the diagnosis, and sixth nerve palsy is ruled out.

Biological basis

Etiology and pathogenesis

Compared to paralytic strabismus, less is known about the pathogenesis of comitant nonparalytic strabismus. The etiology of nonparalytic horizontal strabismus is multifactorial. Genetic and environmental factors are believed to be contributing. Identified risk factors for the development of childhood strabismus include family history, refractive errors, low birth weight, retinopathy of prematurity, maternal smoking in pregnancy, neurodevelopmental disorders such as Trisomy 21, cerebral palsy, and hydrocephalus (32).

Family history is a well-recognized risk factor. Family studies showed approximately 30% of probands with strabismus having a family member or close relative with strabismus. Twin studies showed significantly higher concordance of strabismus in monozygotic twins compared to dizygotic twins (36). Dominant, recessive, and sex-linked inheritance patterns have been proposed for nonparalytic comitant strabismus. In assessing 173 pedigrees involving 1589 people with a family history of congenital esotropia, Maumenee and colleagues (35) found that inheritance was compatible with a Mendelian codominant mode, but the estimated transmission probability was not consistent with Mendelian expectations.

Biological basis. Parikh and colleagues and Rice and colleagues identified comitant strabismus locus in a linkage analysis of two different large families, which showed significant logarithm of the odds (LOD) score on chromosome 7p22.1 (STBMS1) (42; 45). Shaaban and colleagues identified significant evidence of linkage between 4q28.3 and 7q31.2 loci and nonparalytic strabismus. (47). After stratifying cases into esotropia and exotropia subgroups, they identified additional loci at 8q24.21 and 14q21.3, respectively.

Differential diagnosis

Confusing conditions

Apparent (pseudo) strabismus. Prominent epicanthal folds may give a false impression of inward eye deviation, whereas a wide nasal bridge and hypertelorism may give a false impression of exotropia in orthotropic subjects. The light reflex test (Hirschberg test) may be deceiving in patients with abnormal angle kappa with apparent strabismus. Angle kappa is the angle between the visual axis (a line connecting the fovea to the object of fixation) and the central pupillary axis (a line through the center of the pupil perpendicular to the cornea). If the visual axis and the central pupillary axis coincide when the eye fixes on a light, the angle kappa is zero. This is a rare finding as the light reflex is usually 3 to 5 degrees nasal to the center of the cornea and is referred to as a positive angle kappa. This angle is sometimes larger than average, as in a very farsighted or hyperopic patient, and, thus, produces apparent exotropia. Less frequently, the reflex may be deviated temporally, a negative angle kappa that may give the appearance of an in-turned eye. A cover test in which no movement of either eye is noted when a cover is placed before either eye will confirm the diagnosis.

Bilateral sixth nerve paresis. Mild bilateral sixth nerve paresis may result from elevated intracranial pressure. It presents with diplopia and esotropia that may look comitant, and the range of abduction can be indistinguishable from normal. Higher deviation in distance compared to near and slowing of abducting saccades, in addition to other features, may be associated (eg, papilledema and high, increased intracranial pressure symptoms) and help in the diagnosis.

Bilateral internuclear ophthalmoplegia. Mild bilateral internuclear ophthalmoplegia can appear similar to nonparalytic exotropia with full ductions. Subducting nystagmus, slowing of adducting saccades, and abduction overshoot can be helpful for diagnosis.

Associated or underlying disorders

Strabismus in cerebral palsy. Children with cerebral palsy have a high prevalence of strabismus (50% to 90%) compared to neurologically normal children (3% to 4%). Exotropia is the most commonly associated ocular misalignment in children with cerebral palsy, followed by esotropia. Less common forms of strabismus that may exist or coexist in patients with cerebral palsy include hypertropia, hypotropia, dissociated vertical deviation, and dyskinetic strabismus. Dyskinetic strabismus is a peculiar form of strabismus that occurs in children with severe cerebral palsy and is characterized by a reversal of strabismus pattern (eg, from esotropia to exotropia) during the same examination (15).

Previously, strabismus in cerebral palsy was believed to have a poor surgical outcome and a tendency to require repeat surgeries; hence, surgical correction was discouraged. However, subsequent studies have encouraged surgical correction of strabismus in patients with cerebral palsy to decrease potential social ridicule as a result of the strabismus in addition to the motor disability. In fact, studies have shown that patients with cerebral palsy have a similar surgical motor outcome after strabismus surgery, without the need for more frequent reoperations. However, it appears that patients with severe cerebral palsy and developmental delay are less likely to develop binocular fusion and stereopsis and are more likely to have an exaggerated response to surgical dosing, resulting in overcorrection (09).

Strabismus in craniosynostosis. Strabismus is one of the most common ophthalmic associations affecting vision in patients with craniosynostosis. The pathogenesis of strabismus in these patients is related to abnormal orbital shape and derangements in the function or number of extraocular muscles that are common in craniosynostosis. A retrospective study of 726 children with craniosynostosis showed an overall prevalence of strabismus of 36%, 18% (261 children) of whom had exotropia, 12% esotropia, 11% vertical, and 20% inferior oblique overaction. Strabismus risk appeared to increase with the number of fused major sutures (30% for one suture [except for coronal, which was 47%] and up to 70% for all four sutures) (46). Children with strabismus secondary to craniosynostosis are at risk of improper visual development (amblyopia) in addition to other sight-threatening associations, including amblyopia from refractive errors, exposure keratopathy from lagophthalmos (inability to close eyelids secondary to shallow orbits), and optic neuropathy secondary to high intracranial pressure. Amblyopia should be suspected and treated in children with craniosynostosis associated with strabismus to maximize visual gain. There is a debate regarding the optimal timing of surgical correction of strabismus in children with craniosynostosis. Classically, surgery is delayed beyond the first 2 years of age because cranial vault reconstruction may alter the ocular deviation. On the other hand, some pediatric ophthalmologists prefer early surgery as the benefit of achieving binocularity in the first 2 years of life may outweigh the risk of future shifts in ocular alignment (11; 39).

Strabismus in traumatic brain injury. Paralytic strabismus is a common cause of ocular misalignment after traumatic brain injury; however, ocular misalignment can occur following traumatic brain injury from nonparalytic causes, including decompensation of previously controlled phoria, convergence insufficiency, or accommodation spasm. Horror fusionis is an unusual cause of diplopia following head trauma that results from central disruption of binocular fusion. Eyes may be evidently misaligned; however, horror fusionis diplopia can occur in patients with nearly aligned or even perfectly aligned eyes. Diplopia from horror fusionis is hard to treat and may not be curable by either prisms or surgery (01).

Management

Management depends on the diagnosis of the particular ocular misalignment, along with other factors that include the etiology, age of the patient, visual acuity, and family perspectives. Treatment options may include surgical correction, glasses prescription, botulinum toxin, use of eye drops, or a combination of them. Surgical correction of strabismus may be indicated to avoid diplopia, establish binocularity, and for aesthetic reasons. Different surgical techniques are described, which generally depend on weakening one or more muscles, strengthening one or more muscles, or a combination of both.

Infantile esotropia requires surgical correction of the misalignment. The goal of surgery is to align the eyes within 8 to 10 prisms of orthophoria during the first 2 years. The optimal timing for surgical correction of infantile esotropia is still a subject of great debate (19; 24; 48; 05).

Accommodative esotropia requires the full correction of the hyperopic refractive error to correct the deviation. In accommodative esotropia, the true problem lies in an abnormal amount of convergence of the eyes when the child accommodates to overcome his hyperopia and bring the image into sharp focus. Glasses simply act to focus the image on the retina, thus, removing the need to accommodate and allowing good alignment to be maintained. Surgical correction is not an option in fully accommodative esotropia and does not completely replace the role of glasses in partially accommodative esotropia. Families may be disappointed with the persistence of misalignment when the glasses are taken off. The positive side to this form of strabismus is that good vision and sensory fusion is most often possible.

Adjustable suture strabismus surgery techniques allow postoperative fine-tuning of binocular alignment in order to correct for over or undercorrection and can usually be performed same day or first postoperative day. Adjustable suture surgery has been used for many years and is particularly well suited for difficult strabismus cases with unpredictable outcomes, mainly paralytic strabismus. It has also been used for nonparalytic comitant strabismus in adults and in children with varying results compared to regular surgery according to different studies (38; 13). Children may need to be under light anesthesia to perform the adjustment, whereas adjustment of suture is usually done in adults under topical anesthesia (44).

Outcomes

The main outcome measures are the achievement of ocular alignment and binocular fusion and stereopsis. The outcome depends on the type of strabismus, age of the patient, and timing of intervention.

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Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Omar Solyman MD

Dr. Solyman of the Johns Hopkins School of Medicine has no relevant financial relationships to disclose.
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Editor

Heather E Moss MD PhD

Dr. Moss of Stanford University has no relevant financial relationships to disclose.
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Former Authors

Leon-Paul Noel MD and Stacy Pineles MD

Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: male=female
Heredity: Heredity may be a factor
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none

ICD & OMIM codes

ICD-9: Esotropia: 378.00-08

Exotropia: 378.10-18

Intermittent heterotropia: 378.20-24

Hypertropia: 378.31

Monofixation syndrome: 378.34

Accommodative esotropia: 378.35

Convergence insufficiency: 378.83
ICD-10: Esotropia: H50.0

Exotropia: H50.1

Intermittent heterotropia: H50.3

Hypertropia: H50.2

Monofixation syndrome: H50.4

Convergence insufficiency and excess: H51.1

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Nonparalytic horizontal strabismus

Associated Disorders

strabismus in cerebral palsy
strabismus in craniosynostosis
strabismus in traumatic brain injury

Differential Diagnosis

apparent (pseudo) strabismus
bilateral sixth nerve paresis
bilateral internuclear ophthalmoplegia

Also Relevant

Amblyopia
Botulinum toxin treatment of neurologic disorders

Clinical Categories

Patient Handouts

Craniosynostosis

Nonparalytic horizontal strabismus

Introduction

Overview

Key points

Historical note and terminology

Terminology of ocular misalignment:

Measurement methods of strabismus convenient for bedside examination by neurologists include the following:

Clinical manifestations

Presentation and course

Esodeviations

Exodeviations

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Outcomes

Special considerations

Anesthesia

References

Contributors

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Editor

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Patient Profile

ICD & OMIM codes

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