Core Messages

■The result of surgery for infantile esotropia (IE) can be described by the following outcome parameters: (1) the binocular vision conserved or regained by early surgery, (2) the postoperative angle of strabismus and the long-term stability of alignment,and (3) the number of operations needed to reach these goals or the chance of spontaneous reduction of the strabismus into a microstrabismus without surgery. To judge the best age for surgery in a specific child with IE, the expected outcome of surgery should be estimated according to these parameters.

■There have been no studies with prospectively assigned earlyand late-surgery groups and an evaluation according to intention-to-treat, other than the Early vs. Late Infantile Strabismus Surgery Study (ELISSS). The primary outcome of that study was that 13.5% of those operated at approximately 20 months of age against 3.9% (P =

0.001) of those operated at approximately 49 months recognized the Titmus Housefly at the age of 6 years; there was no di erence in stereopsis beyond Titmus Housefly.

■Reoperation rates were 28.7% in the early and 24.6% in the late group. 8.2% of the children scheduled for early surgery and 20.1% of the children scheduled for late surgery had not been operated at the age of 6 years; most developed a microstrabismus. Esotropia less than 14° at baseline at approximately 11 months of age had not been operated at the age of 6 years in 35% of the cases. Hypermetropia around spher. + 4 increased the likelihood of regression without surgery, underscoring the need of full refractive correction.

■Findings of substantially finer stereopsis after very early surgery await confirmation in a randomized controlled trial.

11.1Introduction

11.1.1Definition and Prevalence

Infantile esotropia (IE) is defined as an esotropia with an onset before the age of 6 months, with a large angle of strabismus, no or mild amblyopia, small to moderate hypermetropia, latent nystagmus, dissociated vertical deviation, limitation of abduction, and absent or reduced binocular vision, in the absence of nervous system disorders [1, 2].

IE a ects approximately 0.25% of the population [3–5]. A higher prevalence has been found previously in studies where little distinction was made between

esotropia with and without nervous system impairment. In a recent study among 627 consecutive strabismus patients younger than 19 years [6], 4.8% had congenital esotropia without and 7.0% congenital esotropia with nervous system impairment, including any nervous system impairment except speech delay.

11.1.2Sensory or Motor Etiology

IE may have di erent causes, ranging from sensory to motor defects. Prematurity, low birth weight, and low Apgar scores are significant risk factors for IE [5]. Motor fusion, i.e., translating image disparity information into a

vergence command to facilitate stereopsis, is a complex cerebral function that may well falter in nervous system damage, explaining the bad outcome of early surgery in such cases [7, 8]. On the other hand, if esotropia results

11 from some motor disorder, like a congenital palsy or an anatomical anomaly of an eye muscle or the bony orbit, early surgery may well contribute to regain or conserve binocular vision with fine stereopsis.

As the cause of IE, whether sensory or motor, is the predominant determinant of the degree of binocular vision that may be conserved or regained by surgery, there is a strong need for finer distinction among the subtypes of IE.

IE should be considered, similar to the working definition formulated for congenital cerebral palsy [9], as a group of permanent, but not unchanging, disorders with strabismus and disability of fusional vergence and binocular vision, due to a nonprogressive interference, lesion, or maldevelopment of the immature brain, the orbit, the eyes, or its muscles, that can be di erentiated according to location, extent, and timing of the period of development. Such an open matrix fits both congenital esotropia without nervous system impairment and congenital esotropia with nervous system impairment, and also includes very early cases of accommodative esotropia that overlap with IE.

11.1.3Pathogenesis: Lack of Binocular Horizontal Connections

in the Visual Cortex

In IE, the horizontal binocular connections above and below the input layer in the visual cortex, which link ocular dominance columns of the right and left eyes [10], do not develop (sensory cause) or cannot develop (motor cause). They develop if the inputs from the right and left eye are obtained from corresponding images, facilitating fusional vergence and stereopsis [11–13].

At birth, each eye projects via both visual cortices to the contralateral middle temporal and medial superior temporal area, sensitive to motion and disparity, and responsible for ipsiversive OKR, ipsiversive pursuit, vergence, and gaze holding. Accordingly, infants can follow objects moving towards the nose more easily, the so called nasotemporal OKR and pursuit bias. The ipsilateral middle temporal and medial superior temporal areas are accessed via the binocular horizontal connections in V1 that only develop if binocular vision is possible. When these fail to develop, the nasotemporal bias persists and latent nystagmus develops [14–17]. The duration of the lack of binocular vision determines the

severity of the nasotemporal pursuit asymmetry [18] and of the latent nystagmus [19].

In cats and macaque monkeys made to squint shortly after birth by cutting the medial rectus muscles [10], cutting the lateral rectus muscles [20], or fitting with prism goggles [21, 22], there is a lack of binocular horizontal connections in the visual cortex, correlated with the duration of the lack of binocular vision [22]. The restoration of binocular vision by removal of the prism goggles, simulating early surgery, demonstrated in these animals [18, 22], stresses the feasibility of early surgery in IE cases when its cause is motor. In another animal model, esotropia was found to occur naturally in macaque monkeys [23]. This seems more like IE in children than surgically induced esotropia [24], but many of the macaques had high hypermetropia [23, 24], their accessory lateral rectus muscle was absent [25], or their horizontal recti were twice as large as those of, albeit younger, controls [24].

11.1.4History

Whatever its cause, whether sensory or motor, the end state of IE is characterized by lack of binocular vision, first described by Claud Alley Worth in 1903 [26] when he wrote: “In the human infant the motor coordinations of the eyes are already partially developed at birth. During the first few months of life these serve (in the absence of any disturbing influence) to maintain approximately the normal relative directions of the eyes. … When the fusion faculty has begun to develop, the instinctive tendency to blend the images formed in the two eyes … will keep the eyes straight. When the fusion faculty is fairly well developed, neither hypermetropia, nor anisometropia, nor heterophoria can cause squint. … Sometimes, however, owing to a congenital defect, the fusion faculty develops later than it should, or it develops very imperfectly, or it may never develop at all. Then, in this case, there is nothing but the motor coordinations to preserve the normal relative directions of the eyes, and anything which disturbs the balance of these coordinations will cause a permanent squint.”

11.1.5Outcome Parameters

Several case-series studies opposing this view reported stereopsis in 35–80% after surgery at the age of 0–6 months [27–35]. Current US standard age of first surgery