Intermittent Divergent Squint in Prematurity and Its Neurophysiological Aspects.

Intermittent distance exotropia is a deviation characterized by an exophoria at near fixation and manifest exotropia at distance fixation. There is normal binocular fusional vergence and stereoacuity at near fixation, but the eyes tend to diverge in bright sunlight, tiredness, day dreaming and the patient may close one eye in such circumstances. Prematurity is associated with numerous eye pathology, besides retinopathy of prematurity, amblyopia, refractive errors, it is also associated with a higher risk esotropia and exotropia. We report a case of a 5-year-old girl (preterm and very low birth weight) with an intermittent deviation of both eyes since three years. On her detailed ocular examination diagnosis of divergence excess intermittent exotropia with normal accommodative convergence to accommodation ratio was made. Bilateral lateral rectus recession was done using hang back technique. Postoperatively, the eyes were aligned normally thereby achieving orthotropia. This article reviews various neurophysiological aspects of intermittent divergent squint delineating the etiopathogenesis, classification system, and management options in intermittent exotropia.

INTRODUCTION

There have been many debates regarding the cause of increased strabismus in premature infants. The previous studies have found both birth weight and gestational age to be independent risk factors for strabismus. Prematurity is associated with eye pathology, including retinopathy of prematurity (ROP), amblyopia, strabismus, and refractive errors.[1] When detected early, amblyopia and many other childhood vision abnormalities are treatable.[2] Strabismus is found in approximately 4% of children under 6 years of age. Of these, approximately 25% present with exotropia,[3] most commonly intermittent distance exotropia (IDEX). The onset of IDEX is usually between 12 months[4] and 4 years of age and its characteristic features are unique: normal binocular alignment with binocular single vision is demonstrable for near fixation, but a constant or intermittent exotropia develops for distance fixation. This article hereby reviews the etiopathogenesis, classification system, and management options in intermittent exotropia.

Background

We report a case of a 5-year-old girl with an intermittent deviation of both eyes since 3 years. There was no history of double vision. Antenatal history of her mother revealed preterm (period of gestation 28 weeks) low birth weight (1400 gm) normal vaginal delivery. There was no history of fever, any drug intake or X-ray exposure during her antenatal period. The child developed jaundice in her neonatal period for which she received phototherapy and exchange transfusion. There was no history of any other significant illness. She had been prescribed spectacles of -0.5 Dsp both eyes since 2 years.

Her general physical examination and other systems examination were normal. On her ocular examination, visual acuity in her right eye and left eye was 6/18. On refraction with- 0.5 Dsp both eyes, the visual acuity was 6/12 bilateral eyes. Hirshberg's test showed 40°–45° alternating divergent squint [Figure 1]. On the cover test, no exotropia on near fixation but on distance fixation marked angle alternating exotropia was present [Figures 2 and 3]. Ocular movements were full on testing. The angle of deviation was estimated to be 80 prism diopters (pd) by prism bar cover test which was 90 pd on upgaze and 75 pd on downgaze. AC/A ratio was found to be normal. Hence, the diagnosis of divergence excess (DE) intermittent exotropia with normal AC/A ratio was made. Bilateral lateral rectus recession of 10 mm was done using hang back technique. Postoperatively, the eyes were aligned normally with no deviation on distance fixation [Figures 4 and 5].

Figure 1

Hirshberg's test showing 40°–45° divergent squint

Figure 2

No exotropia on near fixation

Figure 3

On distance fixation marked angle exotropia

Figure 4

Orthotropia achieved after bilateral lateral rectus recession without correction of refractive error

Figure 5

Orthotropia achieved after bilateral lateral rectus recession with correction of refractive error

DISCUSSION

Exodeviations are much more common in latent or intermittent form than esodeviations. Of all the exotropia intermittent exotropia comprises about 50%–90% of the cases and is usually preceded by a stage of exophoria.[5] According to a study by Gulati et al. infants with very low BW were at a 61% increased risk of developing strabismus. The risk for strabismus increased by 13% for every 250 g below a BW of 2500 g.[6] Other strabismus risk factors include anisometropia and refractive error, genetics, older parental age, maternal smoking during pregnancy, neurodevelopmental impairment, low Apgar scores, craniofacial abnormalities and chromosomal abnormalities, in utero toxin exposure, ROP, and cesarean delivery.

The development of visual perception including acuity, color vision, contrast sensitivity, binocular vision, and three dimensional (3D) perception occur during the critical period of development, which corresponds to a period of high plasticity. This plasticity changes with age, with its peak during the first postnatal year. In case of abnormal vision, such as strabismus, during this period, the development of the visual system and of visual perception itself may be greatly altered, in particular regarding the development of an amblyopia and the loss of binocular.

There may be following neurodevelopmental factors leading to IDEX:

Abnormal weakness of extraocular muscles such as muscular dystrophies, genetic myopathies include Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, and Steinert myotonic dystrophy may lead to variable phenotypes of strabismus and abnormalities of ocular movements. In myasthenia, the transmission of neurotransmitters at the level of the neuromuscular junction that is affected which may lead to variable and intermittent forms of strabismus[7]

Abnormal development of neuronal activity-abnormal retinal waves-prenatal spontaneous neural activity in retina is highly structured, and thus allows the transmission of very precise messages to the central nervous system. If retinal waves display abnormality, for any reason, this entire process of development will be disrupted. Prenatal neural bases for binocular integration and/or for acuity would be altered centrally leading to misalignment of the eyes[8]

Abnormal visual perception may induce strabismus-any abnormality within the visual network because of abnormal retinal waves prenatally will lead to an abnormal visual perception, with a central origin[9]

Abnormal balance excitation/inhibition – A balance between excitatory and inhibitory inputs from retina to cortex is required for normal visual perception. Abnormality in this balance, either before or after birth, might lead to abnormal visual perception and uncorrelated eye movements[10]

Abnormal synchronization of neural activity – Any abnormality within one given visual area or between at least two visual areas, due to developmental anatomical and/or functional abnormalities before or after birth in the visual system, may lead to strabismus (and amblyopia and/or binocular vision loss) by altering synchrony

Abnormal development of neuronal activity in oculomotor system abnormal extraocular proprioceptive inputs from extraocular muscles to ophthalmic division of trigeminal nerve, abnormal activity of the vergence neurons and abnormal activity in superior colliculus, cerebellum and/or vestibular pathways may lead to strabismus.[11]

Intermittent exotropia is an exodeviation intermittently controlled by fusional mechanisms. Although exophoria is almost universal, manifest exodeviation or exotropia are rare due to good fusional convergence reserves. It is stated in a study by Worth (1929) that the essential cause of squint is a defect of the fusion faculty and when the fusion faculty is inadequate the eyes are in a state of unstable equilibrium causing strabismus.[12] Initially, these patients were thought to have abnormally have high (approximately 15/1) accommodative convergence to accommodation (AC/A) ratio to account for the reduced ocular deviation at near as compared with that found at a distance.[13] However, now, it has been demonstrated that objectively determined response AC/A ratios in patients with DE exotropia are actually within the normal to high-normal range. This is in agreement with von Noorden's earlier clinical findings using a near-gradient clinical procedure.[14]

AC/A ratio is assessed objectively by following methods:

Gradient method using + 3.00 DS lenses with the following calculation:

The gradient method could not always be measured at each assessment due to patient cooperation; therefore, the AC/A ratio was also calculated for standardization across visits with the heterophoria method using the calculation:

The role of suppression during visual immaturity to overcome diplopia caused by strabismus has been suggested by various authors. Knapp and Jampolsky have postulated a theory that probably there occurs a progression from exophoria to bilateral, bitemporal hemiretinal suppression to intermittent exotropia. This theory holds that the ability to suppress temporal vision allows the eye to diverge.[14151617]

Refractive error is associated in a severity-dependent manner to the prevalence of esotropia and exotropia.[18] In a patient with uncorrected myopia, less than normal accommodative effort is required during near vision thus causing decreased AC and this under stimulation of convergence may cause an exodeviation. In patients with high degree of uncorrected hypermetropia, no effort is made to overcome the refractive error by an accommodative effort and clear vision is unattainable leading to the development of an exodeviation on the basis of an under stimulated and thus under active convergence mechanism that causes the AC/A ratio to remain low.

CLASSIFICATION

The Newcastle Control Score is a reliable, clinically sensitive method for grading the severity of IDEX.

Table 1 shows the components of Newcastle Control Score.

Table 1

Components of Newcastle Control Score

Newcastle Control Score (NCS) was used to grade the extent of IDEX before, during, and after treatment A score of 3 or greater was taken to indicate a requirement for treatment intervention. For those with NCS >3 significantly higher cure rates were achieve with surgery than without.[18]

Burian proposed a classification of intermittent exotropia based on the difference between the distance deviation and the near deviation.[19] He classified intermittent exotropia into four groups: basic pattern, DE pattern, pseudo-DE pattern, and convergence insufficiency pattern [Table 2].

Table 2

Burian's classification of intermittent divergent squint

This classification is based on clinical characteristics and not on the mechanism of the distance-near disparity. The mechanism for the distance-near disparities is most likely related to the superimposition of various types of overconvergence on the basic exodeviation. These convergence mechanisms, as proposed by Kushner, include tonic fusional convergence (tenacious proximal fusion), AC (high AC/A ratio), and proximal convergence (AC/A ratio is normal) [Table 3].

Table 3

Kushner classification of intermittent divergent squint

Another office based scale is devised by Mohney BG and Holmes J both for distance and near fixation.[20]

Intermittent Exotropia Control Scale is applied to each patient for both distance and near fixation which, when combined, yields an overall control score ranging from 0 to 10. Levels 5–3 are assessed during an initial 30-s period of observation. Levels 2–0 are graded as the worst of three rapidly successive trials. An occluder is placed over the right eye for 10 s and then removed; measuring the length of time, it takes for fusion to become re-established. The left eye is then occluded for a 10-s period and the time to re-fusion is similarly measured. A third trial of 10-s occlusion is performed, covering the eye that required the longest time to refuse. The worse level of control observed following the 3, 10-s periods of occlusion should be recorded for that visit. If the patient has a micro-esotropia by simultaneous prism and cover test, but exodeviation by alternate cover test, the scale applies to the exodeviation.

MANAGEMENT

Multiple treatment modalities have been suggested for IDEX. These include orthoptic exercises to improve the near control of the deviation by increasing fusional reserves, part-time occlusion regimes which aim to improve control of the deviation by working against the suppression mechanisms and minus lenses or prisms that can be used to induce convergence, therefore reducing the amount of divergence. In surgical management, there has been various school of thoughts. Some believe that patients may achieve superior sensory outcome with motor realignment before age 7 or <5 years of strabismus duration.[2122] Others state that the surgery needs to be postponed for several years because intermittent exotropia patients can maintain intermittent normotopia and bifixation and that not all intermittent exotropia is progressive. In some cases, the deviation may remain stable for many years, whereas in a few cases, it may even be improved. However, there are other authors that believe that patients might easily achieve binocular function if operated after age 7 and over 5 years of strabismus duration.[2324] There have been various surgical approaches, however, recently, it has been shown that for all types of exotropia except the convergence insufficiency type bilateral lateral rectus recessions work well.[25] It is believed that long-term success requires deliberate short-term overcorrection since eyes tend to drift out over time. Thus, many advocate targeting an initial overcorrection ranging from 4 to 10 pd. Postoperative diplopia is used to stimulate the development of fusional vergences and stabilize postoperative alignment. One must keep the age of the patient in mind when planning surgery since consecutive esotropias in a visually immature infant can have the consequences of amblyopia and loss of binocularity. In older, children and adults who develop intermittent exotropia after age 10 years, diplopia is usually present with little or no suppression. In these patients, the surgical goal should be orthotropia on the first postoperative day, not intentional overcorrection. In addition, adults with longstanding intermittent deviations will often tolerate under correction, but will have symptomatic diplopia when overcorrected.[2526272829]

Prematurity is thus one of an important risk factor for the development of strabismus. When detected early, amblyopia, and loss of binocularity associated with strabismus is treatable. These patients require long-term follow-up even after successful attainment of orthotropia since eyes tend to drift out over time.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Table 4

Intermittent exotropia control scale