Infantile Esotropia 

Updated: May 20, 2021
Author: Vicente Victor Dizon Ocampo, Jr, MD; Chief Editor: Donny W Suh, MD, MBA, FAAP, FACS 

Overview

Background

Strabismus is one of the most relevant health problems of the world, and infantile esotropia is perhaps the most visually significant yet the least understood. Infantile esotropia is the inward deviation of the eyes noted before the patient reaches age 6 months. It is associated with maldevelopment of stereopsis, motion processing, and eye movements. Amblyopia is a frequent consequence of infantile esotropia. Its exact cause has yet to be identified, and an effective treatment strategy is yet to be formulated.

Pathophysiology

The exact cause of infantile esotropia remains unknown. While some opine that esotropia is due to excessive tonic convergence, few agree on what accounts for such conditions. Worth strongly believed that esotropia is an inborn and irreversible defect of fusion. As such, it is a primary dysfunction in the normal development of binocular sensitivity. This was countered by Chavasse who asserted that the neural components necessary for normal binocular vision are present in strabismic individuals at birth, but the development of fusion is eventually impeded by abnormalities of optical input (eg, monocular cataracts) or muscular output (eg, cranial nerve palsies).

The origins of infantile esotropia are just as undefined. A few authors have implicated practically everything from and between the extraocular muscles to the visual cortex in the causation of infantile esotropia.

Although understanding the mechanisms behind infantile esotropia has come a long way, there is still a lot of ground to cover to unearth and clearly understand such an elusive condition.

Epidemiology

Frequency

United States

Strabismus is one of the most prevalent ocular problems among children, affecting 5 in every 100 US citizens, or some 12 million people in a population of 245 million. Infantile esotropia accounts for 28-54% of all esotropias. A population-based study from 1965 to 1994 reports the birth prevalence of infantile esotropia to be 25 per 10,000 or 1 in 403 live births.[1] It is thought to affect about 1% of full-term, healthy newborns and a much higher percentage of newborns with perinatal complications due to prematurity or hypoxic/ischemic encephalopathy.

To determine whether esotropia is present at birth or develops later in infancy, Nixon et al observed 1,219 alert infants in a normal newborn nursery at a city hospital and noted that only 40 babies (3.2%) had esotropia (intermittent esotropia in 17 patients, with 14 patients varying between esotropia and exotropia, and 9 patients with variable esotropia). In addition, no infant displayed characteristic features of infantile esotropia.[2] As such, infantile esotropia is not believed to be connatal but rather develops in the first few weeks or months after birth.

Greenberg et al reported an annual age- and gender-adjusted childhood esotropia incidence of 111 per 100,000 patients younger than 19 years.[3] This rate corresponds to a cumulative prevalence of approximately 2% of all children younger than 6 years, with a significant decrease in older ages. The incidence of childhood esotropia from this population-based study is comparable to the prevalence rates among Western populations. Esotropia is most common during the first decade of life, with the accommodative and acquired nonaccommodative forms occurring most frequently.

Mortality/Morbidity

Exotropia in infancy is believed to be associated with an increased prevalence of coexisting neurologic, ocular, and craniofacial abnormalities. To a lesser degree, infantile esotropia also has been associated with a high prevalence of systemic disorders, including prematurity, neurologic, and genetic disorders. Reports of coexisting brain lesions (eg, periventricular leukomalacia, enlargement of the lateral ventricles with hypoplasia of the corpus callosum, myelination delay at the anterior horn adjacent of the lateral ventricles) have been published.

Age

By definition, infantile esotropia is seen in infants before age 6 months.

 

Presentation

History

Infantile esotropia typically is not present at birth but rather develops in the early months of infancy. Often, the child manifests with chronic inward deviation (esodeviation) of the visual axes at age 2-4 months. This may be preceded by several weeks of transient episodes of misalignment, accounting for the often mentioned history of eyes crossing at birth.

Certain risk factors have been associated with infantile esotropia. Significant among these are prematurity, family history or secondary ocular history, perinatal or gestational complications, systemic disorders, use of supplemental oxygen as a neonate, use of systemic medications, and male sex. The added risks of perinatal complications (eg, prematurity, birth injury, low birth weight) to infantile esotropia have been investigated, yielding equivocal, if not contrary, results. Awareness of these risk factors can lead to early detection and management of esotropia.

Physical

Classic infantile esotropia is constant and involves a large angle of deviation exceeding 20 prism diopters (PD) on corneal light reflex measurement. As a rule, children with constant esotropia of greater than or equal to 40 PD in the first 2-4 months of life rarely resolve spontaneously to orthophoria. In addition, reduction of the angle of deviation below 40 PD is uncommon in these patients.

Children with initially smaller angles of deviation (< 40 PD) or variable angle esotropia have a slightly better chance of resolution to orthophoria. However, 3 cases with infantile esotropia whose angle of deviation decreased spontaneously to less than 10 PD over a minimum follow-up period of 37 months eventually were observed to develop late complications of infantile esotropia (eg, bilateral inferior oblique muscle overaction, latent nystagmus, dissociated vertical deviation).

According to Tychsen, infantile esotropes manifest with a constellation of ocular motor signs, as follows[4] :

  • Esotropia, with or without strabismic amblyopia

  • Pursuit asymmetry

  • Latent fixation nystagmus

  • Motion visual-evoked potential (VEP) asymmetry and motion perception abnormalities

  • A face turn and abduction deficit

  • Dissociated vertical deviation

Infantile esotropia may be associated with a spectrum of clinical presentations, including amblyopia, impaired binocularity, central scotomas, and incomitance.

Amblyopia is relatively common in patients with infantile esotropia. Weakley et al stated that amblyopia should be suspected strongly in patients with esotropia and asymmetric inferior oblique activity, specifically in the eye with more inferior oblique overaction.[5] It has been observed that motor skills are reduced in amblyopic children particularly those with strabismus. Manual dexterity tasks requiring speed and accuracy are affected the greatest. Most clinical evidence suggests that sensory and motor functions are nearly normal if alignment (within 10 PD of orthophoria) is attained within the first 2 years of life.

Virtually all patients with infantile esotropia fail to develop normal binocular vision and stereopsis.

Mohindra et al reported that children with infantile esotropia corrected with prisms equal in size to the deviation showed some degree of binocularity up to at least 2.5 years, as measured by a Polaroid bar stereogram procedure with 1800 seconds of arc disparity; however, all older patients (>6 y) with a history of infantile esotropia failed the test.[6]

On the other hand, studies have shown that compared to an age-matched population, monocular preferential-looking acuity in infantile esotropes was not significantly different during months 3-14 for the preferred eye and during months 3-8 in the nonpreferred eye. Stereopsis and monocular acuity were noted to be significantly lower in the older esotropic patients. These studies showed that deficits in preferential-looking acuity and subsequent amblyopia occur after the onset of fixation preference and that stereoscopic pathways are present and functional in at least some esotropic infants.

Central scotomas almost always are identifiable, even in patients with optimal motor alignment and with the highest levels of binocular vision. On the other hand, it had been stated that the inferonasal quadrant of the visual filed is constricted in patients with infantile esotropia as a result of dissociated vertical deviation. Haefliger et al subsequently refuted this statement.[7]

Incomitance also may be observed. The most common type is the V-pattern infantile esotropia, wherein esodeviation is greater in downgaze than in upgaze. V-pattern infantile esotropia is attributed largely to overaction of the inferior obliques. The reverse of this type, the A-pattern, also may be noted in infantile esotropes.

Causes

The exact cause of infantile esotropia has yet to be identified distinctively. While it strongly is believed that a genetic component exists, a solid basis for linkages among family members still needs to be established. However, several studies have made significant inroads toward establishing a genetic causation for infantile esotropia. Tychsen and Lisberger reported in 1986 that the strabismic patient who had the most severe pursuit/motion processing asymmetry had 2 siblings with infantile esotropia. Furthermore, large-scale investigations have shown that 20-30% of children born to a strabismic parent eventually will develop strabismus themselves. On the other hand, there is a suggested relationship of nonsyndromic infantile esotropia to the susceptibility loci on regions 3p26.3-26.2 and 6q24.2-25.1 and may share alleles that underlie Duane retraction syndrome.[8]

 

DDx

 

Workup

Procedures

Perform the alternate prism cover test to accurately measure the angle of strabismus. This procedure gauges the full magnitude of any combined esotropia and esophoria. Carefully perform a prism cover testing for both distance and near fixation in primary position, with the patient wearing any prescribed spectacle correction. Measurement of the strabismus also is carried out in side and vertical gazes to rule out restriction, palsy, and significant oblique muscle overaction or underaction.

Imaging Studies

Autimated and semi-automated methods of strabismus measurements have recently been developed and validated. These systems were created to provide more objective, faster, and easier alternatives to the manual measurements of strabismus. Such manual measurements are largely dependent on the examiner's skill and experience, especially in more challenging patients such as babies and toddlers. Various attempts have been made towards reducing the variability of manual measurements by standardization through automation including the use of automated image analysis software, videos based on infrared eye tracking, video goggles to perform a Hess screen test, and binocular optical coherence tomography.

A modality based on eye tracking and dedicated full occlusion glasses was developed and tested in chidlren with strabismus. It appeared to be a promising tool for providing precise detection and measurements of ocular misalignment and differentiating between phorias and tropias for children aged 3 years and above. Meanwhile, a semi-automated Hirschberg test-based application was similarly tested for horizontal strabismus, with favorable potential.

 

 

 

 

Treatment

Medical Care

Smaller angles of deviation may be addressed with prism lenses with or without occlusion therapy, depending on the existence of amblyopia. Perform a good refraction with full cycloplegia on infants with esotropia. A common cycloplegic combination is 2.5% phenylephrine and 1% cyclopentolate. It is necessary to occlude one eye at a time during retinoscopy to make sure that the examiner maintains accurate alignment with the visual axis. The average cycloplegic refraction of a child with infantile esotropia with no other developmental or systemic problem is a mild hyperopic spherical equivalent with mild astigmatism, which is relatively stable in the first decade of life.

Corrective lenses generally are prescribed with hyperopia greater than +2.50 diopter (D) and/or when anisometropia exceeds 1.50 D. In addition, any cylinder greater than or equal to +0.50 D should be given spectacles. On the other hand, myopia above -4.00 D warrants corrective lenses. Correcting moderate-to-severe hyperopia is performed to eliminate a significant refractive esotropia superimposing upon a preexistent infantile esotropia. Correction of myopia is performed for 2 reasons. First, it is to clear the images seen by the infant so that it increases the chances of accurate fixation and consequently generates more accurate strabismus measurements. Second, minus lenses may alter the accommodative demand and the infant's strabismus angle, particularly when fixating near targets.

If amblyopia is discovered, appropriate occlusion therapy is instituted at once. The rule of thumb observed is 1-2 weeks of high percentage (eg, 90% of waking hours) occlusion of the nonamblyopic eye per year of life, especially if a strong fixation preference for one eye is detected. The infant is reexamined after a few weeks to determine response to therapy and to ensure that occlusion-induced amblyopia has not developed in the occluded dominant eye. If close, frequent follow-up visits will not be possible, then lower percentage occlusion therapy can be initiated. The endpoint of occlusion therapy is to achieve a pattern of freely alternating equal vision.

Botulinum toxin (BOTOX®) injection into the medial rectus has been explored as an alternative therapy to surgery. Several studies have investigated the merits of such a procedure with contrasting results. In the work using concurrent bilateral medial rectus BOTOX® injections, McNeer et al noted a decrease in the esotropic angle in 27 patients with infantile esotropia younger than age 12 months, from 43 to 1±2 PD, and in patients younger than age 24 months, from 31±12 to 2±3 delta.[9] Long-term studies up to 95 months postinjection follow-up were conducted by the same authors showing not only a significant reduction in esotropic angle but also successful binocular alignment (±10 PD) in 89% of the patients.[10]

In a separate study by Scott et al, it was noted that 65% of the study patients with infantile esotropia achieved correction of 10 PD or less following BOTOX® injection, with smaller deviations (10-20 PD) more frequently corrected than larger deviations (20-110 PD).[11] No globe perforation, amblyopia, or visual loss was reported as a result of the injections. Tejedor and Rodriguez claimed that BOTOX® injection was a rapid and less invasive alternative to reoperation in children who had been treated unsuccessfully with surgery to correct infantile esotropia.[12]

However, not all studies were convincing of the efficacy of BOTOX® injections. Ing contended that alignment by BOTOX® injections appeared to be less effective in establishing evidence for binocularity than incisional surgery in the treatment of congenital esotropia.[13] On the other hand, while Biglan et al agreed that BOTOX® injections may be useful in the management of patients with recent surgical overcorrections, it was not as successful as traditional strabismus surgery for the treatment of infantile esotropia.[14] In a review of randomized controlled trials on the use of botulinum toxin for strabismus, Rowe and Noonan noted that there was no significant difference between the former and surgery for patients with infantile esotropia.[15]

In an evaluation of BOTOX® as primary treatment for infantile esotropia against surgery, de Alba Campomanes et al claimed that BOTOX® was most effective in treatment of small- to medium-angle esotropia, with results comparable to surgery.[16] This was echoed by Gursoy et al.[17] However, large-angle esotropia is still best managed with surgery.[18] Meanwhile, Lueder et al suggested BOTOX®–augmented medial rectus recession to be a viable treatment for large-angle esotropia, with stable results over time.[19]

Surgical Care

Infantile esotropia is characterized by large angles of deviation (>40 PD) and customarily is corrected surgically. Tychsen stressed that when the surgeon has documented that the infant has a constant esotropia exceeding 12 PD, surgical realignment should be performed.[4] The surgeon must obtain 2 reasonably high-quality reproducible strabismic measurements, which agree to a range of 5-10 PD, before proceeding with the operation.

Over the years, a number of surgical techniques have been developed, but most of them involve bilateral medial rectus recession, wherein the insertion of the muscles into the globe is transferred posteriorly consequently weakening their adducting action. An alternative is a unilateral medial rectus recession - lateral rectus resection (shortening of the muscle leading to increased abducting power). A randomized comparison of the effectivity of the two procedures noted no significant difference.[20] Variations in technique depend on the total number of muscles initially involved (eg, 2, 3, or 4, wherein lateral rectus resection or shortening also is performed) and the amount of medial rectus recession carried out. The hang-back technique is noted to be just as effective as conventional bimedial rectus recession.[21]

For large angle (>55 PD) infantile esotropia, bilateral medial rectus muscle recession and one lateral rectus muscle resection can be performed, and this has been shown to have a high success rate.[22]

Adjustment of the amount of correction is just as important. Chang et al described a one-stage intraoperative adjustment of strabismus surgery with adjustable sutures to be a simple, well-tolerated, and effective procedure.[23]

A controversial issue is the timing of surgery.

In the final report of the Early vs. Late Infantile Strabismus Surgery Study (ELISS), children operated at age 6-24 months had better gross stereopsis at age 6 years compared with those operated on later; however, more reoperations were done in the former group.[24] Zak and Morin claimed that corrective surgery from age 5-24 months produced successful alignment of the eyes to within 10 PD of orthophoria, with a higher prevalence of fusion and stereopsis and a lower prevalence of dissociated vertical deviation (DVD).[25] This was reiterated by Yagasaki et al, who noted that early surgery decreases the severity of DVD and lowers the need for additional operation for DVD.[26]

While the beneficial effect of accurate alignment by age 2 years has been well established and widely practiced, the earliest age at which surgery should be performed has yet to be defined convincingly. Whether or not to undertake alignment procedures before age 1 year has triggered much debate and vigorous investigations. Studies have shown that performing strabismus surgery at or before age 10-11 months enhances sensory and ocular motor development and that strabismus surgery does not need to be delayed while waiting for the angle of deviation to be stabilized. Furthermore, inferior oblique overaction and amblyopia were less frequent when the initial operation had been performed before age 12 months. The Congenital Esotropia Observational Study suggests performing early surgery to children with large-angle constant infantile esotropia at or before age 10 months.[27]

Shirabe et al concurred with such findings but added that it was necessary to confirm a stable angle of deviation with accurate preoperative evaluation and to maintain good postoperative eye alignment throughout the follow-up period to achieve and maintain the binocular visual function resulting from early corrective surgery.[28] Birch et al explained that better stereopsis is achieved with early surgical alignment because the duration of misalignment is shortened and not because alignment is achieved during an early critical period of visual maturation.[29] Surgery for infantile esotropia is most likely to result in measurable stereopsis if patient age alignment is not more than 16 months.[30]

The long-term outcome of early surgical correction of infantile esotropes (mean postoperative follow-up period is 14.7±3.7 y) showed that an eventual loss of binocular alignment occurred in some patients but at a much later age, with reduced chances of developing oblique muscle overactions. Children who undergo surgical alignment at age 6 months have a higher prevalence of coarse stereopsis than those who are corrected surgically at age 7-15 months.

Moreover, in a separate study of infantile esotropes who underwent surgical alignment before age 1 year, 3 distinct groups were defined, as follows: (1) those who remained stable following their initial early alignment, (2) those who were well aligned and remained stable for prolonged periods of time and then decompensated, and (3) those who were unstable throughout the observation period.

These findings illustrate the instability of the conditions of patients with infantile esotropia. While apparent benefits with regard to improved binocularity and visual acuity had been demonstrated with early surgical correction of infantile esotropia, a need exists for repeated thorough observations in the first decade of the patient's life.

Over the years, new surgical modalities have been proposed to address childhood esotropia and concomitant ocular problems in children.

Lueder and Norman performed strabismus surgery as an alternative to bifocal glasses in treating accommodative esotropia with favorable results.[31] They concluded that strabismus surgery may eliminate the need for bifocal glasses in patients with accommodative esotropia with a high accommodative convergence/accommodation (AC/A) ratio.

Ticho et al noted that simultaneous extraocular muscle and lens surgery is an option for patients with strabismus and lens abnormalities.[32] The authors recommended using standard strabismus surgical amounts. Very few postoperative complications were reported.

Godts et al reported that preoperative intermittent or manifest strabismus was not a contraindication for refractive surgery, provided some specific recommendations are taken into account, such as an adequate preoperative orthoptic examination and a goal of emmetropia for both eyes.[33]

In summary, infantile esotropia greatly affects eventual binocular alignment and binocular vision. A delay in surgical correction could result in loss of stereopsis. Waiting for the angle of deviation to stabilize prior to surgery does not greatly affect overall postoperative outcomes. Early surgical intervention is essential in producing better outcomes in terms of sensory and motor development, binocular vision, and stereoacuity.[34]

Consultations

Consultation with a pediatric ophthalmologist may be indicated.

Activity

Upon fully recovering from general anesthesia, the child is allowed to roam and play freely. Parents can bathe and wash the patient's face without undue concern, especially if a fornix approach was used for the incision. Occlusion therapy is discontinued during the first postoperative week. However, spectacles should be worn during this time.

 

Medication

Medication Summary

Very few medications are used in the treatment of infantile esotropia. Combination antibiotic-steroid ointments are prescribed for the first postoperative week. BOTOX® injection has been used as an alternative to initial or repeat surgical ocular alignment.

Combination antibiotic-steroid ointments

Class Summary

Used in first postoperative week to control any inflammation and to prevent any infection resulting from surgery, particularly in the conjunctiva.

Dexamethasone/tobramycin (TobraDex)

Consist of 0.3% tobramycin and 0.1% dexamethasone. Tobramycin has been found to be active against numerous gram-positive (eg, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae) and gram-negative organisms (eg, Pseudomonas aeruginosa). Dexamethasone is a potent corticoid.

Neurotoxins

Class Summary

Botulinum toxin type A (BOTOX®) is most commonly used. Inhibits transmission of nerve impulses in neuromuscular tissue.

OnabotulinumtoxinA (BOTOX®)

Blocks neuromuscular conduction by binding to receptor sites on motor nerve terminals, entering nerve terminals, and inhibiting the release of acetylcholine. Intended for injection into extraocular muscles. Initial doses administered in 1.25-2.5 U. Use lower doses for smaller deviations and larger doses for larger deviations.

 

Follow-up

Further Outpatient Care

The infant typically is seen 3-14 days after the surgery. Visual acuity is checked, an afferent pupillary defect is ruled out, and a good red reflex is elicited from both fundi. Furthermore, conjunctival incisions are inspected with a penlight for dehiscence and infection. Most importantly, alignment is assessed, and eye movements are observed for gross underaction and a slipped muscle. If no excessive inflammation is noted, use of antibiotic-corticosteroid ointments may be stopped at this time.

Surgical correction is the first step in the visual rehabilitation of children with infantile esotropia. Patients who are aligned successfully early in life still need careful postoperative monitoring for amblyopia, nystagmus, inferior oblique overactions, dissociated vertical divergence, and accommodative esotropia.

A follow-up visit usually is scheduled 3-4 months after the initial postoperative consult. At this point, occlusion therapy can be restarted if amblyopia is present. In cases of significant overcorrection or undercorrection, while the patient may be seen earlier, reoperations seldom are performed before the third to fourth month postoperative period. If alignment is optimal (eg, within 8 PD of orthophoria) and acuity is equal in both eyes, subsequent follow-up visits are scheduled every 6-12 months until age 7 years. At this point, the risk of strabismic amblyopia is decreased, and yearly visits are sufficient. After age 10, consultations are performed on an as-needed basis.

Accommodative esotropia may develop following surgical correction of infantile esotropia. In a study by Uretmen et al, it was noted that accommodative esotropia occurred at a mean of 8.8 months (range, 6-24 mo) after the initial surgical alignment, with a mean age of onset of 43.2 months.[35] Correction with the appropriate lenses must be instituted to prevent the adverse effects of accommodative esotropia on sensory and motor functions.

Inpatient & Outpatient Medications

Aside from the antibiotic-steroid ointment used in the immediate postoperative period, no other medications are needed.

Complications

Complications of initial surgical correction of infantile esotropia include the following:

  • Marked overcorrection and undercorrection

  • Infection

  • Scleral perforation

  • Foreign body granuloma at the suture site

  • Allergic reaction to suture material

  • Conjunctival inclusion cyst

  • Conjunctival scarring

  • Anterior segment ischemia

  • Change in eyelid position

  • Lost muscle

  • Slipped muscle

  • Oculocardiac reflex

Prognosis

It is accepted that better ocular alignment and visual prognosis can be achieved if surgical correction is performed before age 2 years. Long-term follow-up studies on esotropic infants who underwent surgical alignment by age 2 years have shown that close to 60% achieve a small angle (< 20 PD) cosmetically acceptable strabismus. Although some binocular vision is achieved, it generally is subnormal, often involving peripheral fusion. Factors contributing to poor ocular alignment and visual prognosis include persistent preoperative amblyopia, latent manifest nystagmus, and myopia from -2.5 to 5.0 D.

Patient Education

Parents and other caregivers must be educated on the various presentations of infantile esotropia to ensure early detection and management.