Infantile esotropia is a constant, comitant, large-angle esotropia that develops within the first 6 months of life. The deviation is usually 30 prism diopters (PD) or more. It was formerly called “congenital esotropia,” but in recent years, the term “infantile esotropia” has been adopted because it is not necessarily present from birth.
The incidence is approximately 1/400 to 1/50 in newborns, and abroad it is estimated at about 25 cases per 10,000 births. There is no sex difference. It is one of the most difficult-to-treat types of strabismus in terms of binocular vision acquisition. About 70–75% of newborns are born with exophoria or exotropia, but eye alignment begins to improve around 2–3 months of age and becomes nearly orthotropic by 6 months.
Esotropia of 40 PD or more does not resolve spontaneously. The US PEDIG study reported that among infants confirmed to have esotropia of 40 PD or more at 2–4 months of age, spontaneous resolution occurred in 0/45 and 0/21 cases 1). The CEOS study diagnostic criteria require confirmation of esotropia of 40 PD or more on two visits spaced at least 2.5 months apart 1).
If an esotropia of 40 PD or more is confirmed at 2 to 4 months of age, spontaneous resolution is unlikely. The PEDIG study found no cases of spontaneous resolution 1). Early ophthalmologic consultation and determination of treatment strategy are important.
The infant does not complain of pain or discomfort. The main reason for consultation is the parent noticing a misalignment of the eyes.
Large-angle esotropia is the main finding, and several associated findings are common. Since accommodative esotropia occurs in about 60% of cases after infantile esotropia surgery, preoperative cycloplegic refraction is important.
Main Findings
Constant esotropia: Large angle of 30 PD or more. If the angle exceeds 45 PD and onset is confirmed before 6 months of age, it is likely essential.
Cross fixation: Fixation with the right eye to the left and the left eye to the right. Differentiation from abduction limitation is necessary.
Amblyopia: Occurs in about 40-50% of cases. Assessed by fixation preference. If there is no alternating fixation and a preference exists, the risk of strabismic amblyopia increases.
Associated Findings
Dissociated vertical deviation (DVD): Occurs in 50-90% of cases. The non-fixing eye elevates during occlusion. Usually appears after 1-2 years of age.
Inferior oblique overaction: Occurs in about 70% of cases. Observed as elevation during adduction.
Fusion maldevelopment nystagmus syndrome (latent nystagmus): Complicated in about 40% of cases. It is a horizontal jerk nystagmus induced by occlusion of one eye, with the fast phase directed toward the non-occluded eye.
OKN asymmetry: Shows asymmetry where pursuit in the temporal-to-nasal direction is persistently dominant.
Patients who show alternating fixation often have preserved monocular visual acuity, but binocular visual function is generally poor.
The etiology is unknown. Several hypotheses suggesting an association with neurodevelopment have been proposed (see “Pathophysiology and Detailed Mechanisms” section for details).
The following are known risk factors:
A family history of strabismus is listed as one of the risk factors, suggesting the involvement of genetic predisposition. However, specific inheritance patterns or causative genes have not been identified. It is frequently observed in children with neurodevelopmental disorders such as prematurity, cerebral palsy, and hydrocephalus.
Cycloplegic refraction and a complete ophthalmologic evaluation with pupillary dilation are necessary.
The most important differentiation is from pseudoesotropia. In East Asians, pseudoesotropia is often caused by epicanthal folds and a flat nasal bridge, making cover test confirmation essential.
| Disease | Key Differentiating Points |
|---|---|
| Pseudoesotropia | No deviation on cover test. Epicanthal folds, flat nasal bridge. |
| Accommodative Esotropia | Onset at 1–3 years, hyperopic background, reduction of ≥10 PD with glasses. |
| Congenital abducens nerve palsy | True abduction limitation exists |
| Duane syndrome type I | Narrowing of palpebral fissure and globe retraction on adduction |
| Nystagmus blockage syndrome | ENG shows jerk nystagmus with decreasing slow-phase velocity on abduction |
Other differential diagnoses include Ciancia syndrome, Mobius syndrome, sensory esotropia, and infantile myasthenia gravis.
In principle, surgical correction is necessary. Once the diagnosis is confirmed, prompt correction is desirable.
Amblyopia is associated in approximately 40-50% of cases. Occlusion of the healthy eye is the basic treatment, and it is not necessary to complete amblyopia treatment before strabismus surgery. However, in cases where eccentric fixation amblyopia or abnormal retinal correspondence is suspected, amblyopia treatment should be prioritized.
If hyperopia of +2.00 D or more is present, full correction with spectacles should be attempted. In cases with moderate strabismus angle, wearing a membrane prism is useful for simultaneous stimulation of both foveae.
Timing of Surgery
Ultra-early surgery: Aim for before 8 months of age. Highest rate of stereopsis acquisition.
Early surgery: Up to 2 years of age. Results are good, second only to ultra-early surgery.
Cutoff: Reports indicate that the rate of stereopsis acquisition drops significantly after 16 months of age1).
No need to wait for stable deviation angle: Lueder (2008) showed that it is not necessary to wait for the deviation angle to stabilize1).
Surgical Procedures
Bilateral medial rectus recession: Standard procedure. The amount of recession is determined according to the deviation angle. There are measurement methods from the medial rectus insertion and from the limbus.
Quantitative (limbus-based): For deviation angles over 45 PD, the approximate recession amount is 10 mm before 6 months, 10.5 mm before 12 months, and 11 mm before 24 months. In infantile esotropia, the distance between the medial rectus insertion and the limbus is known to be significantly shorter than normal (usually 5.5 mm) and not constant, so the limbus-based measurement method has higher reproducibility.
Three-muscle surgery: For large angles, lateral rectus resection is added1).
Postoperative management: For fixation nystagmus, occlude the dominant eye; for residual esotropia of 8 PD or more, use a membrane prism.
Stereopsis begins to develop from 2 to 4 months of age and reaches about 80% of that of healthy adults by 2 years of age. Restoring eye alignment within this sensitive period promotes the acquisition of binocular vision.
Injected into the medial rectus muscle. The effect lasts about 2 to 3 months and is considered more effective in cases with a deviation angle of less than 30 to 35 PD. It is also used as an adjunctive treatment for residual esotropia after surgery1).
Very early surgery (before 8 months of age) is most advantageous for achieving stereopsis. Some reports indicate that the rate of stereopsis acquisition drops significantly after 16 months as a cutoff 1). However, decisions must be made based on each case’s condition and comorbidities, and it is important to discuss thoroughly with the attending physician.
The reoperation rate is high at 15–30%. It is reported to be 60–80% for surgery at 1 year of age and about 25% for surgery at 4 years, with earlier surgery tending to have a higher reoperation rate 1). Under-correction and over-correction are the main causes, and regular postoperative follow-up is important.
Several theories have been proposed regarding the pathophysiology of infantile esotropia.
In experiments using primate models, early eye alignment correction restored normal eye movements and binocular vision, whereas delayed correction resulted in persistent esotropia, latent fixation nystagmus, DVD, and OKN asymmetry 1).
Richards (2007) reported that persistent esotropia for 6 months or more increased monocular connections threefold compared to binocular connections 1).
Gerth (2008) reported that in the group that underwent surgery before 11 months, normal mVEP was obtained, whereas in the group that underwent surgery at 11–18 months, abnormal and asymmetric mVEP persisted 1).
Many studies have accumulated on the relationship between timing of surgery and binocular visual function.
| Study | Number of Cases | Stereopsis Acquisition Rate (Early vs Late) |
|---|---|---|
| Birch & Stager 20001) | 129 cases | 6-month alignment: 100% / Over 1 year: 8% |
| ELISS 20051) | 58 European centers | Early group: 13.5% / Late group: 3.9% |
| Yagasaki 20201) | Multiple groups | Very early: 77% / Early: 20% / Late: 13% |
Birch & Stager (2006) reported that the early surgery group achieved fusion in 77.8% and stereopsis in 14.8%, compared to only 61.4% and 2.3% in the standard group 1).
Yagasaki (2011) reported that in the ultra-early surgery group, all DVD cases were latent, whereas in the late surgery group, 38.9% progressed to manifest DVD 1).
Shin (2014) reported that late surgery was associated with an odds ratio of 8.23 (P<0.001) for the risk of developing spontaneous DVD 1).
Drover (2008) reported that after surgery, faster sensorimotor and gross motor development was observed compared to age-matched controls, indicating that surgery for infantile esotropia also contributes to non-visual development 1).
Trikalinos (2005) used a Markov model analysis to show that the benefits of early correction outweigh the risk of reoperation 1).
Advantages of ultra-early surgery (before 8 months of age) include improved rates of binocular visual function such as stereopsis and fusion, DVD remaining latent (suppressing manifestation), and promotion of sensorimotor and gross motor development 1). Although the reoperation rate is higher, the benefit of acquiring binocular visual function is considered to outweigh the risk.
