Intermittent exotropia [X(T)] is a unique type of strabismus. In X(T), the sensory visual system fluctuates from normal binocular reflexes and stereopsis when the eyes are aligned, to suppression when the eyes are misaligned, and back again. The presence and size of the misalignment and the suppression scotoma may vary depending on the fixation distance. Amblyopia does not usually occur. Despite the absence of diplopia, individuals with X(T) often seem to recognize when their eyes are out of alignment (by mechanisms that are unclear) and are able to pull them back into line when prompted.
X(T) generally arises early in childhood and is not usually associated with neurodevelopmental abnormality. Some, but not all, children with the condition close one eye, especially in bright sunshine. It is not entirely clear why this occurs. Children with X(T) normally present for medical attention because of parental concern about the ocular misalignment or eye closure. Nonsurgical treatments are of uncertain value, and surgery, although often effective, carries the risk of persistent overcorrection, with amblyopia in younger children and diplopia in older children.
For these reasons, X(T) is a condition deserving of further study, and this article will attempt to present the current state of knowledge and suggest future directions for research.
Little is known about the etiology of X(T). In contrast to infantile exotropia and infantile esotropia, X(T) is not associated with prematurity or developmental delay, nor is it associated with significant refractive error or amblyopia. X(T) superficially bears some resemblance to dissociated horizontal deviation, except that dissociated horizontal deviation occurs in the context of binocularity disrupted by early-onset constant strabismus.
Few animal studies exist, but reduced metabolic activity in the visual cortex has been noted in macaque monkeys that had divergent strabismus induced by disinsertion of the medial recti, suggesting suppression in the deviated eye and suppression of the temporal retina in the fixating eye. In animals with weak fixation preference, there were cortical signs of alternating suppression.1
Excessive active divergence has been suggested as a cause of X(T), with one study showing increased lateral rectus activity in the deviated eye when the eye diverges, but not in the fixing eye.2 However, the existence of active divergence is controversial.
X(T) is the most common form of exotropia. In a recent study, 205 children with exotropia were identified in a 10-year period in one U.S. county corresponding to an annual age-adjusted incidence of 64.1/100,000 patients younger than 19 years, and a prevalence of 1% in children younger than 11 years.3
Whereas esotropia is more common in white populations,4 exotropia is twice as common as esotropia in Asian populations.5 X(T) seems to be more common in girls.6
The onset of X(T) is usually before 5 years, and may be as early as the first year of life. Children with X(T) usually present for medical attention because of the observed intermittent deviation, which is usually initially apparent during periods of tiredness or inattention, or on distance fixation. An alternative manifestation of the condition is monocular eye closure that occurs in bright illumination.7 Why this occurs is unknown; it is believed to be related to photophobia and is not thought to be a means of avoiding diplopia.8,9
Children with X(T) do not generally complain of diplopia, although they sometimes notice panoramic vision. Despite the presence of suppression, amblyopia is rare because the eyes typically remain aligned, fixing at near, usually with good binocular function and stereopsis.
Although X(T) is normally noticed at distance fixation, the near deviation can be as large as the distance deviation. If the near deviation is larger than die distance deviation, the diagnosis is convergence insufficiency, a different condition. If the deviation measured on an alternating prism cover test remains larger at distance fixation (by 10 prism-diopters [pd] or more), despite attempts to increase the near deviation by suspending accommodation or tenacious proximal fusion,10 then the X(T) is termed "divergence excess" X(T). If the alternating prism cover test measurements at near and distance are within 10 pd of each other, then the X(T) is termed "basic." If the measurements at near and distance are within 10 pd of each other only after suspending accommodation or tenacious proximal fusion, then die X(T) is termed "simulated divergence excess."
In the past, these distinctions were considered important. Bilateral surgery was necessary for divergence excess X(T), whereas unilateral recess/resect surgery was the appropriate procedure for basic and simulated divergence excess X(T). It is not clear that this distinction in management is necessary11 and neither is it clear that the three types of X(T) are biologically distinct, given that an X(T) at distance only may evolve into a constant exotropia at distance and near, via progressive loss of control of the deviation at near.
The differential diagnosis includes infantile exotropia, decompensated exophoria, near exotropia (convergence insufficiency), and sensory and consecutive exotropia. The most challenging of these are infantile exotropia and sensory exotropia in small children in whom measures of uniocular visual acuity are difficult to obtain. The author has recent experience with two small children presenting with apparent X(T), one of whom had a blind eye due to optic nerve glioma, and the second, a retinoblastoma. Similarly, showing the progression of X(T) to exotropia in small children, in whom stereo tests and simultaneous prism cover tests are difficult to perform, can be problematic.
One school of thought holds that X(T) is often a progressive condition that can result in irretrievable loss of binocular vision,12"14 whereas another holds that X(T) frequently does not progress.15"17 Reported series of individuals with X(T) will be biased in favor of those whose parents are seeking treatment. Furthermore, the performance of surgery is not a valid proxy marker for progression because it is heavily influenced by parental observation and concern, with consequent variability in rates between different surgeons.18
One author has stated: "The currently foggy concept of natural history creates insurmountable obstacles in evaluating the benefits of various forms of intervention - both surgical and non surgical."19
CLINICAL ASSESSMENT AND MANAGEMENT
There are two reasons for treating X(T): cosmetic or psychosocial and functional. There are currently no objective criteria for evaluating the former, whereas there are a multitude of criteria for evaluating the latter.
The primary functional consequence of X(T) is a reduction in distance stereo acuity. Although this is measurable, its functional significance is uncertain. Using the Binocular Visual Acuity Test (B-VAT; Mentor, Norwell, MA), Stathacopoulos et al. reported a reduction in distance stereo acuity in X(T),20 with the same group reporting an improvement after treatment.21 The B-VAT is no longer commercially available, and it was difficult to use with younger children. The Frisby-Davis Distance Stereotest (FD2) is a recently developed, childfriendly, free space test of stereo acuity22 that is currently being evaluated in X(T). It should be noted that the reporting of stereo data, on both near and distance tests, is problematic because the data are not normally distributed and some individuals will have a value of zero. Assigning such individuals an arbitrarily large value (eg, 1,000 seconds of arc) to include them in the analysis will cause bias and possible misinterpretation.
Although many parameters, including the size of deviation on alternating prism cover test at near and distance, convergence, binocular visual acuity,23 motor fusion and fusional vergences, and near stereo acuity, have been proposed as important to monitor in X(T), there is no consensus about their use, or on the action required if the results of the different tests do not correlate with each other. Surgery is generally considered as a result of measures of control of the deviation.24 Measures of control usually include parental assessment of the frequency with which the misalignment is apparent and observations of how quickly realignment occurs after disruption of fusion. These measures have drawbacks, however.
Parental observations of control may only take place at times of day when the child is tired if he or she is of school age, and may be manipulated by parents who want, or do not want, intervention. It is not clear how monocular eye closure should be addressed. Realignment after a cover test may be influenced by fatigue and inattention.
To allow for easier monitoring of the control of X(T), the criteria described by Rosenbaum and Stathacopoulos24 have been elaborated into a score, the Newcastle Control Score for Intermittent Exotropia25 (Table 1). This scoring system has shown some promise as a method of monitoring control and response to treatment in X(T),26 and it may prove useful in longitudinal studies.
ACTIVE MANAGEMENT OPTIONS
Conservative treatments for X(T) include correction of refractive errors, minus lenses, orthoptic exercises, and occlusion. These are most frequently used as a temporizing measure in young children who are vulnerable to the effects of surgical overeo rrection and in small-angle (< 20 pd) X(T).
Significant refractive errors, even hyperopic ones, should be corrected in X(T), because this correction will sharpen the retinal images and improve fusion.
Lenses of power 2 to 4 diopters over minus have been reported to aid control of X(T) in approximately one-half of patients studied,26,27 and they do not appear to induce myopia.28 They may be particularly helpful in patients with high accommodative convergence/accommodation ratios.29 However, parents sometimes believe that the psychosocial consequences of wearing overminus lenses may be as bad as those of the X(T).
Orthoptic exercises are a mainstay of treatment of convergence insufficiency. They have been claimed to be of use in X(T), but do not appear to be used often in practice.30,31 Occlusion, usually of the fixing eye, is used more commonly and has its advocates.31,32
X(T) is frequently treated surgically.14 Factors to be taken into consideration include the age of the patient, the accommodative convergence/ accommodation ratios (which may be difficult to measure in small children), the presence of significant oblique muscle overactions, distance/near disparity, and lateral incomitance. Surgical tables do not generally distinguish between different types of exotropia. A surgical table that the author has found helpful for X(T) is shown in Table 2. Basing the surgery on postocclusion and far distance measurements,33 prism adaptation,34 and medial rectus Faden suture in children with high accommodative convergence/ accommodation ratios35 have all been reported to improve results.
Some studies have shown better outcomes after surgery for X(T) if there is an initial postoperative overcorrection.36,37 Such overcorrections induce diplopia, even in young children, often leading to the adoption of an abnormal head posture. It is not known what the optimum period of overcorrection is to maximize enduring postoperative alignment, but overcorrection causes concern if it does not resolve within a few days. The optimum time for intervention if diplopia does not resolve is not known, but in younger children, suppression and amblyopia may develop rapidly. This may be compatible with a cosmetically acceptable result. Refractive correction, prisms, and botulinum toxin may be helpful if overcorrection persists.
As a result of the dangers of overcorrection in younger children, some authors recommend deferring surgery until the visual system is relatively mature,18,38,39 whereas others believe that cure rates are better with early surgery.12,40
Bilateral surgery has been recommended for divergence excess X(T), whereas unilateral recess/resect surgery has been advised for basic and simulated divergence excess X(T).41 However, the two procedures appear to have the same effect on distance/ near disparity11 in patients with basic exotropia.
There is evidence that X(T) can recur long term after surgery.42
The goal of surgery in X(T) is constant orthotropia with normal sensory function.43
It is apparent from this discussion that the management of X(T) could be improved if practitioners were to adopt a common set of criteria, accessible to statistical analysis, to evaluate and manage X(T), and act on the results. Such a prospective study, Improving Outcomes in Intermittent Exotropia (the IOXT study), is currently underway in the United Kingdom.
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