Strabismus is misalignment of the eyes. Although it justifies attention at any age, the breadth and depth of an infant's visual development during the first year of life makes the management of strabismus more critical then compared with later in childhood.1
Strabismus is classified by both the direction of the deviation and the frequency of the deviation; the direction determines the prefix, the frequency sets the suffix. An esodeviation occurs when the eyes are turned toward each other (ie, the visual axes intersect in front of the child), an exodeviatíon is present when the eyes turn away from each other. When one eye is higher than the other, a fryperdeviation is present.
A constant strabismus is termed a "tropia" (esotropia, exotropia). If the deviation is latent except when binocularity is preempted or compromised, then a "phoria" (esophoria, hyperphoria) is present. A hypertropia is usually named for the higher eye (eg, if the right eye is higher, it is a right hypertropia).
RELATIONSHIP TO BINOCULARITY
The use of visual input from each eye simultaneously is loosely termed binocularity.2 This is dependent on a learned set of sensory reflexes that can be developed only if there is no gross misalignment of the visual axes. Binocularity has three interrelated components: simultaneous perception, fusion, and stereopsis. Fusion can be developed only if there is simultaneous perception, and this is the constituent part that permits "fine-tuning" of ocular alignment with a motor component. Stereopsis is the ability to directly perceive distance via simultaneous binocular input. It occurs only when fusion is also present. Stereopsis is often used interchangeably with the less specific "depth perception." The latter is the set of perceptive monocular cues with which we judge the distances of objects. Throughout this article, all three components (binocularity, stereopsis, and depth perception) are discussed in the aggregate as binocularity or binocular vision.
When the eyes are aligned, binocularity develops rapidly during the first few months of life and continues to do so at a gradually decreasing rate through much of the first decade. For binocularity to develop, each eye must be developing monocular vision on a normal or near-normal level, and the visual axes must be approximately aligned. If these conditions are satisfied, then as binocularity develops its motor component (fusion) can further "fine-tune" the alignment. This will further enhance binocular development, which further develops binocularity.
If strabismus appears after binocular development has begun, double vision will result from the ocular misalignment. In young children, however, sensory adaptations (suppression and anomalous retinal correspondence) develop to alleviate this disturbing symptom. These adaptations remain in force until the strabismus is eliminated, keeping the child free of diplopia (but binocularly deficient), because both fusion and stereopsis are not possible in this altered state. Of the various reasons to treat strabismus, it is the recovery of these higher degrees of binocularity that provides the major justification.
Closely related to strabismus is amblyopia, which refers to poor visual development in the presence of normal retinal and neurologic anatomy - it is a disorder of function, not structure.3 Amblyopia usually has one of three general causes (in decreasing order of severity): visual deprivation (eg, cataract or corneal opacity), strabismus, or anisometropia (asymmetric refractive error between the eyes). Because monocular visual development is also occurring at a rapid rate during infancy, amblyopia must be ruled out in any infant (or young child) with strabismus. If amblyopia is found, the mainstay of treatment is occlusion of the non-amblyopic eye with a patch applied to the periorbital skin for several hours per day. The duration depends on the severity or depth of the amblyopia. This treatment continues for weeks to months, until the amblyopia resolves.
THE FIRST 3 MONTHS
During the first 3 months of life, eye position can be variable.4 If examined closely, many newborns will exhibit a small exotropia (outward deviation). However, any low-magnitude static deviation is possible.5 Transient eye movement abnormalities of almost any kind can also be seen during this period, including nystagmus and opsoclonus. Both small-angle static deviations and these transient movement abnormalities are insufficient reasons for further neurologic or ophthalmologic evaluation when they occur in this early period of development. Their appearance later in infancy, however, should prompt referral for further evaluation. Referral to a pediatric ophthalmologist is also indicated during infancy (or later) if any strabismus is constant (or nearly so) or of a large magnitude. The variability of eye position mentioned earlier will generally produce only small-angle strabismus; deviations of larger magnitude may be indicative of paralytic strabismus of neurologic origin, or could imply a unilateral visual loss.
Figure 1. Pseudoesotropia.
Many infants, especially those of Asian heritage, will have a "false appearance" of esotropia resulting from an optical illusion (Fig. 1). Infants have a flat nasal bridge early in life. The skin that will eventually cover the lateral aspect of the nasal bridge in later years overlays the adjacent area and obscures the nasal sclera. Under conditions of casual observation, a normal amount of lateral (temporal) sclera can be seen and a corresponding amount of symmetrical nasal sclera is anticipated. The absence of visible nasal sclera will cause most observers to mentally "explain" that appearance by believing that the eyes must be turned toward each other.
The diagnosis of this pseudoesotropia can be made by comparing the relative positions of a light reflex from a standard penlight in each eye. When a child with straight eyes looks at a penlight held by the examiner at a comfortable distance (approximately Vi m), the corneal reflection should be in approximately the same central position in each eye when viewed from directly behind the light source. In true strabismus, the relative positions of the light reflexes will differ. For example, if a true esotropia is present, one light reflex will be approximately centered in the cornea and the other will be temporally decentered (because the eye is deviated in the opposite direction). This effect can often be seen in family photographs, especially when they are brought to the examination to support the parents' claim that their infant's eyes are "crossed." If this penlight test cannot consistently demonstrate the absence of a true strabismus in a child older than 3 months (ie, if the pediatrician is not sure), then referral for a complete evaluation would be indicated.
Figure 2. A large right esotropia.
NONPARBTIC or NONRESTRICTIVE strabismus
Strabismus can result from a partial or complete paralysis of one of the three cranial nerves that innervate extraocular muscles (the third, the fourth, and the sixth). The magnitude of the resulting strabismus will generally vary with gaze, with the largest deviation occurring in the field of action of the affected nerve or musde(s). This pattern of variability is termed "incomitance," to distinguish it from the much more frequent variety of strabismus (unrelated to a nerve weakness) where the angle of deviation remains the same across all gaze positions. Incomitant, or "paralytic," strabismus often has a neurologic cause, and is discussed separately later in this article. Comitant (or nonparalytic) strabismus is usually unrelated to any neurologic disease and therefore does not generally require a systemic neurologic evaluation.
The type of strabismus that occurs when the eyes deviate toward each other (esotropia) is the most common strabismus in infancy. There are two basic types of esotropia, nonaccommodative (which is unresponsive to eyeglasses for hyperopia) and accommodative (which can be successfully treated with eyeglasses to correct hyperopia).
A constant, large-angle esotropia is the hallmark of the classic syndrome mislabeled as "congenital esotropia" (Fig. 2).6 It is almost never truly congenital, but instead develops by 3 to 4 months and always before 6 months of age. Because it prevents stimulation of any binocularly innervated cortical cells (a critical early step in the development of binocularity), the presence of "congenital" esotropia precludes any binocular development. Binocularity will develop only if the visual axes are surgically aligned before approximately 24 months of age. Beyond this point, significant binocular development will not commence, even if the eyes are successfully aligned. For this reason, infants with a constant esotropia need prompt evaluation by a pediatric ophthalmologist (or an ophthalmologist with experience in treating infants). Delayed treatment will lead to less optimal sensory results.
Some children with congenital esotropia will cross-fixate (ie, they use the right eye to look to the left, and the left eye to look to the right). When this occurs, amblyopia develops infrequently, because each eye is relied on approximately half of the time. Children with congenital esotropia who do not cross-fixate will often have an amblyopia. This is manifested as a fixation preference. The parents will report that one eye is crossed more than the other. As outlined previously, the concurrent amblyopia must be treated as well, in this case before the esotropia is treated.
When a constant, large-angle esotropia is seen, referral to a pediatric ophthalmologist is indicated. During the initial evaluation, any accommodative component to the esotropia will be sought and treated with eyeglasses if found. Any amblyopia, as manifested by a fixation preference, will be treated with occlusion of the undeviated eye.
The classic treatment for congenital esotropia is surgical realignment of the eyes. This is done either by weakening each medial rectus muscle (recession) or weakening one medial rectus muscle and strengthening (by shortening or resection) its antagonist lateral rectus muscle.
Accommodative esotropia accounts for most esotropia that begins after infancy. However, this form may still begin during the first year of life.7 This esotropia results when the normal synkinetic response to visual stimulation at near is also used for looking at a distant object.8
Under normal circumstances, the eyes are "at rest" for distance viewing, meaning that the focusing mechanism (accommodation) is completely relaxed. When an object is being viewed at close range, accommodation must be stimulated to increase the focusing power of the eyes' natural ("crystalline") lenses. The eyes must also move toward each other so that the visual axes can converge on this close object. This esotropia is normal and, in fact, necessary to avoid double vision at this close distance. As if for convenience, the convergence automatically accompanies this focusing, or accommodation; their relationship is governed by the accommodative convergence to accommodation (AC/ A) ratio that generally produces six times as much convergence for each unit of accommodation. In circumstances where accommodation is needed without convergence, another mechanism exists to counteract the convergence and avoid double vision. This convergence antidote is called fusional divergence, and it allows the neutralization of convergence to maintain single vision, or fusion.
Accommodative esotropia results from the use of this near synkinetic response in an "off-label" fashion. Most children, including infants, are hyperopic or farsighted and soon learn that the blur from their hyperopia can be cleared by accommodation, even for distance fixation where convergence is not required. Most of these children with hyperopia use their fusional divergence to counteract the unwanted convergence (that accompanies accommodation) to maintain alignment when they accommodate, or focus. Hyperopic children with deficient (or absent) fusional divergence will be unable to neutralize accommodative convergence. Hence, they will be esotropie whenever they clear their vision by focusing (accommodating). Because more focusing is required for looking at near objects, the esotropia in such affected children is usually more apparent when they look at very near objects. This will be reflected in the parents' reporting that the deviation occurs while feeding, for example.
Successful treatment of this condition requires suppression of accommodation. This is best achieved by optical means. The use of eyeglasses (or, less conveniently, contact lenses) focuses a distant image on the retina and removes the blurred image as a stimulus for accommodation. With little or no need for accommodation, no accommodative convergence is produced and the resulting esotropia is eliminated. The appropriate optical prescription is determined during a complete ophthalmologic evaluation using a procedure called a "refraction." After drops that produce cycloplegia (ie, paralysis of accommodation) have been instilled, the total hyperopia of the child is measured with a retinoscope. Lenses of the appropriate strength can then be prescribed. The child does not need to verbally identify images with this technique.
Exotropia is deviation of the eyes away from each other (Fig. 3). Apart from the low-magnitude, transient exotropia seen in neonates (discussed previously), it is uncommon during infancy.910 Exotropia can result from a partial or complete third nerve palsy, and is seen slightly more often in infants with developmental delay of various causes. In those cases, improvement of the exotropia can parallel development.
The most common type of exotropia seen in children is a progressive intermittent exotropia.11 This usually appears during the third or fourth year of life, but is occasionally observed in infancy. The parents will usually report that it occurs with long-distance fixation (which may explain its absence during the first year because infants rarely look at distant objects), or else when their child is tired, ill, or daydreaming. A manifest exotropia for looking at objects at close range, such as when feeding or looking at books, indicates significant progression of the disorder.
Figure 3. Exotropia.
When an exotropia is manifest in a brightly lit environment (eg, outdoors on a sunny day), the usual adaptive mechanisms that eliminate diplopia in young children with strabismus can be "overloaded" and double vision results. This can prompt the child to close one eye in this situation. When reported by the parents, such unilateral "squinting" is significant and suggests definitive treatment is needed.
When the deviation is infrequent (noted by the parents only weekly), intermittent exotropia can be treated expectantly. In some cases, it will improve spontaneously. If this deviation progresses in a child who is otherwise developmental^ normal, surgical correction is often indicated. This is because many nonsurgical treatments that can be performed on older children are difficult to perform on infants. Eyeglasses (with or without prisms) and orthoptic exercises are sometimes useful for the older child with exotropia, but infants lack the cooperation, concentration, or both needed for these therapies to work. The only nonsurgical treatment that can be used in infants is intermittent occlusion. This works by interfering with the development of the compensatory mechanism (suppression) that alleviates the resulting diplopia. With no suppression, the exotropia produces diplopia. This diplopia is a strong stimulus, causing the child's motor component of fusion to counteract the exotropia.
The possibility of amblyopia is a factor in the decision regarding surgery for intermittent exotropia. Unlike in esotropia (where amblyopia is common), amblyopia is infrequent in intermittent exotropia. The indication for surgical treatment of exotropia exists because of the significant risk to binocular development. However, a possible complication in any operation for strabismus is overcorrection (a strabismus in the opposite direction). Should that occur, men a condition that only rarely causes an amblyopia (exotropia) has been replaced by one where amblyopia occurs regularly (esotropia). Overcorrections and undercorrections of strabismus may be more likely during the first year of life because accurate preoperative measurements of the deviation are more difficult to obtain then. This possibility of a complicating amblyopia should at least be considered in the decision whether to operate, but this probably would be overshadowed if the risk to binocular development of the untreated exotropia were significant.
The surgical treatment options in exotropia are similar to those in esotropia. One muscle in each eye can be weakened or recessed (in this case, the lateral rectus muscle). Or, the lateral rectus muscle can be recessed and its antagonist, the medial rectus muscle, can be strengthened by shortening or resection.
PARALYTIC AND RESTRICTIVE STRABISMUS
Disorders of alignment or motility may also result from a palsy or paresis of one or more of the cranial nerves that innervate the extraocular muscles, or from a mechanical restriction of one of those muscles. A nerve weakness will usually cause an obvious misalignment in straight-ahead gaze (the primary position) that varies with gaze position (ie, incomitance). Nerve palsies seen in the first year of life are often "congenital" and unrelated to a neurologic cause. However, some are postviral, and a few result from trauma, tumor, aneurysm, or other neurologic conditions that can produce these abnormalities in older children and adults.
Mechanical muscular restrictions often leave alignment intact for the primary position, but cause incomitant motility problems that vary with gaze position. These can also be secondary to trauma or inflammatory conditions during infancy, but only rarely.
A paralytic strabismus can occur as a result of weakness or paralysis of either the third, the fourth, or the sixth cranial nerve.12 The third nerve innervates the superior, medial, and inferior rectus muscles and the inferior oblique muscle. The fourth cranial nerve innervates the superior oblique muscle, and the sixth nerve controls the lateral rectus muscle. A congenital palsy can occur in any of these alone or in combination. Congenital fourth nerve palsy occurs most often.
A fourth nerve palsy compromises the superior oblique muscle. The loss of its depressing action results in vertical deviation. In addition, this usually causes a head tilt to the opposite shoulder. This can become evident when the child starts to sit unsupported. For this reason, an ophthalmologic evaluation should be part of the evaluation of any infant with torticollis.13 Congenital fourth nerve palsies generally do not resolve spontaneously. They require treatment when the resulting torticollis becomes consistent to prevent spinal complications from the head tilt.
Sixth nerve palsies also occur during infancy, but are generally benign and usually unrelated to any sinister diagnosis. They often resolve spontaneously in weeks to months. The resulting lateral rectus palsy may easily be confused with the much more common congenital esotropia (discussed previously). This distinction is important, because no definitive treatment will be required for a sixth nerve palsy that will resolve, but surgery is always needed for a true congenital esotropia. During the resolution phase, supportive treatment with intermittent occlusion to the unaffected eye may be required to deal with any developing amblyopia.
Third nerve palsy is the least frequent in this group. This is fortunate because it has the most profound effect on alignment and motility and the lowest incidence of spontaneous resolution.14 Because the third nerve innervates muscles that move the eye in both horizontal and vertical directions (and move the upper eyelid), a third nerve palsy creates the largest misalignment(s) and the largest corruption of motility. A complete third nerve palsy will produce exotropia (from paralysis of the medial rectus muscle), hypotropia (from unopposed vertical action of the nonparetic superior oblique muscle against the paralyzed superior and inferior rectus and the inferior oblique muscles), and ptosis of the upper lid. Amblyopia can occur from the resulting strabismus or from ptosis of the upper lid, when present.
The need for neurologic evaluation is minimal when a third nerve palsy is present immediately after birth, especially if the palsy is isolated (ie, without other neurologic abnormalities). An onset any time after that should prompt a thorough neurologic evaluation, even if unaccompanied by other neurologic findings.
Surgery is almost always indicated.15 It often involves muscle transposition procedures to effectively compensate, at least in part, for the multiple effects on motility and alignment. The only feasible goal is normal primary position alignment, because normal motility cannot be fully restored.
Because restrictive syndromes may not affect alignment in primary position, their presence may not be noticed during the first year of life. Only the two more common entities, Duane's syndrome and Brown's syndrome, are discussed here.
Duane's syndrome was named for Alexander Duane, a prominent New York ophthalmologist in the early 20th century. However, this syndrome was actually described 20 years earlier by Stilling and Turk.16 The most common variant, type I, causes little, if any primary position misalignment but is noted when the child attempts to look toward the affected side. Because of miswiring between the third and the sixth cranial nerves, as reported in the few autopsy specimens studied, the affected eye will not move laterally (abduct). When compared with the normal medial movement (adduction) of the unaffected eye, an esotropia is apparent. When the condition is severe, a small esotropia in primary position can result, forcing the child to turn his or her face to the opposite side so that straight-ahead gaze can be maintained. Bilateral cases are unusual but more obvious.
When Duane's syndrome is detected in infancy, a thorough hearing evaluation is necessary because nerve deafness is a systemic association of developmental significance. Other systemic associations include a preauricular skin tag with or without complete Goldenhar's syndrome, Klippel-Feil syndrome, cervical vertebral anomalies, and auricular malformations. Surgery for Duane's syndrome is indicated only if primary position alignment is altered because this causes a compensatory head position, as noted previously.
Brown's syndrome17 was described in the middle of the past century by Harold Whaley Brown. Because of restriction of the superior oblique muscle tendon, the affected eye cannot elevate in the adducted position (when the superior oblique muscle should relax). This motility abnormality is seen only when the child looks up and to the contralateral side. Because most infants and young children will move their heads to look in that direction, a diagnosis of Brown's syndrome is infrequently made in infancy.
When the restriction is severe, primary position alignment can be affected when the eye is forced slightly downward due to the tight or short superior oblique tendon. This causes the affected child to tilt his or her head upward to maintain gaze straight ahead. Should this occur, surgical relaxation of the tendon is indicated.
Infantile strabismus demands vigilant attention because its effect on the rapidly developing visual system can be profound and lifelong. Binocularity will not develop properly, or at all, unless the eyes are aligned during this early, critical period of development. Strabismus is also a common cause of amblyopia, which in severe cases can lead to legal blindness in one eye. These effects from ocular misalignment are much more easily and successfully treated in young children.
The most common strabismus in infancy is the transient misalignment seen in infants up to 3 months of age. This does not require treatment or evaluation. A Pseudostrabismus from a wide nasal bridge, broad epicanthal folds, or both is also common and requires nothing other than reassurance. The most common type of true strabismus is esotropia. This usually requires surgical correction. Infrequently, infantile esotropia will be accommodative in nature and respond to eyeglasses. Congenital palsies of the third, fourth, and sixth nerves can occur and result in strabismus. When isolated, these palsies generally do not require further evaluation; if accompanied by any other findings, then a neurologic evaluation is required.
1. Nelson LB, Rubin SE, Wagner RS, Breton ME. Developmental aspects in the assessment of visual function in young children. Pediatrics. 1984,73375-381.
2. Parks MM. Binocular vision. In: Tasman W, Jaeger EA, eds. Clinical Ophthalmology, vol. 1. Philadelphia: Lippincott Williams & Wilkins; 1998:1-7.
3. Von Noorden GK. Binocular Vision and Ocular Motility, 5th ed. St. Louis, MQ Mosby; 1996:216-254.
4. Cassidy L, Taylor D, Harris C Abnormal supranudear eye movements in the child: a practical guide to examination and interpretation. Suro Ophthalmol. 2000;44:479-506.
5. Nixon RB, Helveston EM, Miller K, Archer SM Ellis FD. Incidence of strabismus in neonates. Am } Ophthalmol. 1985;100:798-801.
6. Nelson LB, Wagner RS, Simon JW, Harley RD. Congenital esotropia. Suro Ophthalmol. 1987;31:363-383.
7. Coats DK, Avilla SW, Paysse EA, Sprunger DT, Steinkuller PG, Somaiya M. Early-onset refractive accommodative esotropia. Journal of the American Association of Pediatric Ophthalmology and Strabismus. 1998;2:275-278.
8. Von Noorden GK. Binocular Vision and Ocular Motility, 5th ed. St. Louis, Ma Mosby; 1996:303-308.
9. Rubin SE, Nelson LB, Wagner RS, Simon JW, Catalano RA. Infantile exotropia in healthy children. Ophthalmic Surg. 1988;19:792-794.
10. Biglan AW, Davis JS, Cheng KP, Pettapeice MC. Infantile exotropia. / Pediatr Ophthalmol Strabismus. 1996;33:79-84.
11 . Hidaji F, Nelson LB, Olitsky SE. Exodeviations in childhood. Ophthalmology Clinics of North America. 1996;9:185-197.
12. Rubin SE. Paralytic strabismus. In: Yanoff M, Duker JS, eds. Ophthalmology. London: Mosby International; 1999:1-10.
13. Rubin SE, Wagner RS. Ocular torticollis. Surv Ophthalmol. 1986;30:366-376.
14. Ing EB, Sullivan TJ, Clarke MP, Bunde JR. Oculomotor nerve palsies in children. J Pediatr Ophthalmol Strabismus. 1992;29:331-336.
15. Gottlob I, Catalano RA, Reinecke RD. Surgical management of oculomotor nerve palsy. Am J Ophthalmol. 1991;111 :71-76.
16. DeRespinis PA, Caputo AR, Wagner RS, Guo S. Duane's retraction syndrome. Surv Ophthalmol. 199338:257-288.
17. Wilson ME, Eustis HS Jr, Parks MM. Brown's syndrome. Surv Ophthalmol. 198934:153-172.