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Intermittent exotropia: continued controversies and current management

Lavrich, Judith B.

Current Opinion in Ophthalmology: July 2015 - Volume 26 - Issue 5 - p 375–381
doi: 10.1097/ICU.0000000000000188
PEDIATRICS AND STRABISMUS: Edited by Bruce M. Schnall
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Purpose of review Continued controversy exists regarding intermittent exotropia and its management. Although it has been studied extensively, the indication for and timing of intervention and what therapy is most efficacious remains unclear. This article reviews the most recent research and the controversies surrounding the disease classification and treatment options in the management of intermittent exotropia.

Recent findings Current studies are underway to uncover the natural history of the intermittent exotropia. Patching and observation are reasonable treatment options in the first 6 months of the disease presentation. As the disease progresses and nonsurgical management fails, botulinum toxin may play a role or be an alternative option in the early treatment of intermittent exotropia. Surgical treatment with orthoptic therapy may result in improved postoperative outcomes.

Summary Although significant investigations have been performed on this entity, there remains poor cohesiveness between clinical trials resulting in lack of clarity regarding when and how to treat intermittent exotropia. As the natural history of the disease is elucidated and researchers standardize their assessment of the control of the strabismus and what constitutes a successful treatment outcome, better understanding may occur to develop more efficacious remedies. Despite being less known and utilized, botulinum toxin and orthoptic therapy are options for treatment for intermittent exotropia and should be considered for appropriate patient's treatment protocol.

Wills Eye Hospital, Clinical Instructor of Ophthalmology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

Correspondence to Judith B. Lavrich, Department of Pediatric Ophthalmology and Strabismus and Ocular Genetics, Wills Eye Hospital, Thomas Jefferson University, Philadelphia PA, USA. Tel: +215 943 7800; e-mail: jblav123@gmail.com

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INTRODUCTION

Exodeviations occur frequently in the normal population from birth to adulthood and more often appear in a latent or intermittent form than esodeviations. Intermittent exotropia (X(T)), the most common form of divergent strabismus, is seen in 60–70% of normal infants, is transient, and usually resolves in the first few months of life as the attention required to maintain binocularity improves [1]. Small exophorias are found in high frequency in adults. Controlled by fusional or accommodative convergence, these exophorias remain asymptomatic. Sometimes preceded by a stage of exophoria, X(T) is also controlled by fusional mechanisms but, unlike a phoria, spontaneously breaks down into a manifest deviation. Although X(T) has been discussed extensively in the literature, there still remains significant controversy regarding the indications for intervention, the optimal time for treatment and the most effective treatment for this prevalent strabismus.

Box 1

Box 1

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BACKGROUND

Epidemiology

Approximately 5% of developmentally normal children develop strabismus, and, of these, 25% are exotropias [2]. The incidence of X(T) in one United States county in Minnesota, studied over a 10-year period, has been reported as 32.1/100 000 in children under 19 years of age, and it occurs with increased frequency in populations of Asian, Middle Eastern and subequatorial African descent [3–5]. It has been reported that the nearer a country is to the equator, the higher the prevalence of exodeviations [5]. A recent study reported that X(T) affects females twice as often as males [6]. One retrospective study showed an association of mental illness with X(T), reporting that children with this strabismus, especially males, were almost three times more likely to develop a psychiatric disorder later in life [7].

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Natural history

The natural history of X(T) remains unclear. As there is a paucity of longitudinal prospective studies and only a few retrospective studies delineating the course of untreated X(T), there is insufficient evidence that X(T) solely develops from a deteriorated phoria. The course of the disease also remains obscure as authors have reported conflicting results from the exotropia improving [8], showing no change [9,10] or decompensating overtime [6]. A multicenter, randomized controlled study is currently in progress with the objective of reporting the natural history of this disease and has a completion date in 2015 [11].

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Presentation and classification

Intermittent exotropia is frequently noted in infancy or early childhood as an outward deviation of one eye typically when viewing a distant object. The tropic phase occurs with greater frequency during periods of inattention, in bright sunlight and when the child is stressed, fatigued or ill. Transient closure of one eye in bright sunlight and photophobia are seen in more than 50% of patients [12]. Diplopia rarely occurs in the younger child as the brain suppresses the eye during the periods of manifest deviation. When intermittent exotropia develops in children beyond age 10, diplopia can be a predominant presenting symptom as they have not developed these sensory adaptations. The incidence of amblyopia has been reported to be 4.5% and 12.8% in children with intermittent exotropia [13,14].

Measurement of X(T) is made using the prism cover test at distance and near. A prolonged alternate cover test or monocular occlusion should be used in patients with X(T) to suspend tonic fusional convergence and uncover the maximum misalignment. A prospective study showed that combining monocular occlusion with far distance measurement can greatly reduce surgical undercorrections [15]. A satisfactory outcome was obtained in 86% of patients using the largest angle for surgery measured at far distance compared with 62% who were measured at a standard 6 m distance. If there is significant variability in the angle of deviation or if there is a significant distance/near discrepancy then monocular occlusion for 30 min is necessary to further relax fusional convergence. Following occlusion, the exotropia should then be remeasured to reveal the actual amount of the deviation. A recent study showed that 1 day of diagnostic monocular occlusion resulted in a significant change in the angle of exotropia in divergent excess-type and convergence insufficiency-type X(T) as well as patients with hyperopia [16]. In a patient with a distance deviation of greater than 10 prism diopters more than the near deviation, a +3.00 D near add test (lens gradient method) should be employed, but only after monocular occlusion. The +3.00 D near add test is used to relax accommodative convergence which avoids misdiagnosing a high AC/A (accommodative convergence/accommodation) ratio when measuring the near deviation [17]. In patients with true divergence excess due to high AC/A ratio, the exotropia at near increases by 20 prism diopters or more with a +3.00 add.

The severity of X(T) is determined by the magnitude of the angle of the exotropia, the ability to control the deviation and the measurement of stereopsis, as an indicator of the quality of single binocular vision. Those patients with large angles of deviation, poor control of their strabismus or reduced stereovision, or a combination of these properties, have traditionally been considered to be more severe. However, quantification of severity has been poorly standardized. The Newcastle Control Score for X(T) was developed to grade the severity of the distance deviation incorporating subjective parental report of control (home control) with an objective criteria (clinic control) (Table 1) [18,19]. This scale has shown to be a reliable method of monitoring control and response to the treatment [20]. More recently, Mohney and Holmes [21] have developed an easy-to-use control scale using distance and near measurements in the office that eliminates the potential error in parental observation and opinion of control and may ultimately become the standard for future studies (Table 2).

Table 1

Table 1

Table 2

Table 2

Two classification systems for the intermittent exotropia have been proposed by Burian and Kushner. Burian's system is based on the concept of fusional convergence and divergence and relies on the measurements of the distance and near exotropia (Table 3) [22]. Kushner's system is more complex and is based on the mechanism of the distance-near disparity which is related to various types of overconvergence superimposed on the basic exodeviation (Table 4) [17]. These convergence mechanisms include tonic fusional convergence (tenacious proximal fusion), accommodative convergence (high AC/A ratio) and proximal convergence (normal AC/A ratio). These classification systems have been used to guide patient evaluation and treatment approaches based on the patient's subtype.

Table 3

Table 3

Table 4

Table 4

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MANAGEMENT OPTIONS

Nonsurgical treatments

Spectacle correction of refractive error

Significant anisometropia, astigmatism, myopia and even hyperopia [23] can impair sensory fusion and promote a manifest deviation in intermittent exotropia. Correction of these refractive errors will often help control of the frequency of the deviation and may cause it to become phoric. Full correction in myopic patients will promote active accommodative convergence. In hyperopia, special consideration should be given to the age of the patient, the extent of hypermetropia and the AC/C ratio, as correcting even small amounts of hyperopia may decrease the accommodative convergence and worsen the exodeviation.

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Observation

In the absence of reduced visual acuity or amblyopia, there still remains considerable controversy of proper treatment course for X(T). Recent studies have shown that observation only is a valid course of action for these patients [24,25▪▪]. In a study of 327 children in the United Kingdom, 53% were observed without any treatment and the findings revealed that the majority of these children remained stable with no associated deterioration in their strabismus but also no clinically significant improvement [24].

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Patching

The first large prospective randomized study attempting to determine the effectiveness of part-time patching for treatment of X(T) found that deterioration of the clinical picture over a 6-month period is uncommon with or without patching treatment [25▪▪]. The participants were randomized to patching were treated with patching one eye or patching the eyes alternately at the investigators’ discretion. No mention was made of the frequency of the deviation or whether one eye had more preference for fixation (amblyopia). Although there was a slightly lower deterioration rate with patching (0.6%) than with observation alone (6.1%), it was determined that both treatment options are reasonable for treating children 3–10 years of age with X(T). With the limited follow-up and the nondefinitive conclusion, the study offers some support for the efficacy of patching but the results are not significant enough for physicians to change their practice patterns. More long-term studies are needed to delineate if the study findings persist with time.

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Minus lenses

Overminus lens therapy induces accommodative convergence and is sometimes used as temporizing measure in X(T) to promote fusion and delay surgical correction. There have been few studies addressing the treatment of X(T) with overminus lenses. However, a more recent prospective study with 5-year follow-up showed 52% of 21 patients achieved a successful or good outcome with overminus lenses alone [26]. The patients were initially treated with −1.00 to −3.00 lenses and after improvement in the angle of deviation and/or binocular function was noted the power of the lenses was reduced. The study found that in the short term (median 4 months), there was 100% improvement in the angle of deviation and binocular function. In the intermediate term (6–24 months), the lens power could not be reduced without recurrence of the X(T). Some cases required further treatment but others showed a smaller angle of deviation which was cosmetically acceptable with good binocular function. In the long-term (median 2.5 years), five patients achieved exophoria at near and distance fixation with good binocular function and this was maintained for at least 1 year after cessation of the treatment. The study showed no induced myopia from the minus lenses.

Overminus lens therapy can be considered as a primary treatment in X(T), especially in the short-term. They may be particularly useful in those patients with X(T) who have a high AC/A ratio or in patients who have a small-angle consecutive exotropia after strabismus surgery. Overminus lenses may cause asthenopia in older children.

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Orthoptic therapy

The Convergence Insufficiency Treatment Trial produced sound scientific data to support orthoptic therapy for the treatment of convergence insufficiency [27]. It has also has been shown to be effective in the treatment of convergence insufficiency-type X(T) with a maximum deviation of 25 prism diopters [28]. In this prospective study of 30 patients, although the exodeviation remained essentially unchanged, orthoptic therapy achieved significant symptomatic relief and improved binocular function. Beyond 25 prism diopters, there was no significant improvement in symptoms. A more recent retrospective study of 74 patients utilized office and home-based therapy with prism exercises, pencil push-ups, 3D tests and dominant eye occlusion and showed improvement in 88% of patients with basic-type of X(T), 88.8% of patients with divergence excess-type X(T) and 100% of convergence insufficiency-type X(T) [29]. Success was defined as relief of presenting symptoms associated with improved exodeviation or an exotropia less than 10 prism diopters.

Especially for convergence insufficiency-type and possibly other types of X(T), orthoptic therapy appears to be a viable treatment option. There are now computer-based orthoptic programs that are easily accessible and can be used at home by patients. However, it remains unclear as to which patients will respond to this therapy, what orthoptic exercises are most efficacious, how long and at what frequency does orthoptic therapy have to be performed for maximal efficacy and what is the long-term stability of these results. Therefore, most patients with X(T) are not offered this therapy at this time. Although orthoptic therapy has been used for the management of X(T) for over 50 years, there still remains a lack of large prospective, randomized scientific studies demonstrating its effectiveness and answering these questions.

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Botulinum toxin

Studies have shown efficacy in using botulinum toxin in the treatment of X(T) noting that it is at least as effective as surgical outcomes, irrespective of the initial strabismus angle, and is particularly efficacious in children between 2 and 4.5 years [30]. After 6 months of follow-up, significant improvement in fusion control and improvement in stereovision have been reported after botulinum toxin injection to the lateral rectus muscles [31▪▪]. A low incidence of complications (12.4%) was found with injections in the horizontal extraocular muscles and included transient vertical deviations (2%), subconjunctival hemorrhages (1%) and ptosis (8.4%), with all complications resolving by the 6-week follow-up [32].

Before Botox [Allergan, Inc. (acquired by Actavis March 2015, Parsippany, NJ, USA)] became a household word for cosmetic procedures, the initial research on botulinum toxin A was performed by Alan B. Scot MD for the treatment of strabismus [33]. Many reasons why botulinum toxin has not commonly become the first-line therapy for the management of strabismus include the paucity of randomized controlled trials, the time required to realize the full effect of the injections, some uncertainty about dosing the medication, the expense of the toxin and practioners’ inexperience with using it. However, this treatment is rapid, less invasive and has the benefit of not altering the extraocular muscles which preserves future surgical options in the event of recurrence. Botulinum toxin has been and remains an effective therapy for the management of strabismus, including X(T), however, long-term studies are needed to assess the stability of its results with time.

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Surgical treatment

Indication for surgery

There remains no clearly defined threshold for patients when considering surgical intervention in X(T). Commonly considered are increasing angle of exodeviation, worsening control or frequency of the exotropia, inability to fuse and maintain stereovision and the presence and severity of symptoms. Recent work has attempted to further elucidate the decision to perform strabismus surgery for children with X(T). After accounting for poor control of the exodeviation at distance, a retrospective study of 106 children reported that children with X(T) whose accompanying parent reported poorer health-related quality of life (HRQOL) were more likely to undergo surgery than those who reported better HRQOL [34▪]. Both the parents’ concern about the child's ability to function and their psychosocial concern about their child were associated with the decision to perform surgery. Of the clinical measures, the distance control, near control and near angle of deviation were found to be associated with the decision for surgery. Another study recognized that there is a high variability of control in X(T) throughout the day and even within minutes and that, if using control of the strabismus as the clinical decision to perform surgery, several assessments of are necessary to provide a representative measure [35].

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Type of surgery

There has been an on-going debate in the literature as to what surgical procedure constitutes the best treatment for X(T). Traditionally, bilateral lateral rectus recession (BLRecess), unilateral lateral rectus recession (ULRecess), medial rectus resection (MResect) and unilateral lateral rectus recession combined with medial rectus resection (R&R) have been used as the standards of surgical treatment. Even with comparisons of the larger cohort studies the conclusions of which procedure is most efficacious remain weak. Within the last several years, this debate has continued with many recent studies targeting outcomes of specific types of X(T). In 85 children with basic-type X(T), it was found that R&R was more effective than BLRecess resulting in better surgical alignment and less undercorrections [36]. In a retrospective study of 128 patients, surgical outcomes after 2 years were assessed in basic-type X(T) and found to be similar with R&R and BLRecess [37]. However, this study showed the final outcomes were better in the BLRecess group than the R&R group possibly due to the lower recurrence rate of exotropia in the BLRecess group.

In a retrospective study of 180 children with moderate angle X(T) of 20–25 prism diopters, ULRecess was compared with R&R and both procedures were found to be similar in the surgical outcomes [38▪]. After more than 2-years follow-up, surgical success was achieved in only 60.9% ULRecess patients and 56.1% R&R patients which the authors found disappointing. They reported that direct comparison of their success rates to other similar studies was not possible due to the lack of similarity between the studies including different lengths of follow-up and criteria for surgical success. This was echoed in a literature review of surgical outcomes over the last 10 years finding lack of harmony in outcome reporting was counterproductive and the authors suggested four core features for reporting for future studies: alignment, near stereoacuity, control score and quality-of-life measure [39▪].

Another study on surgical treatment showed that an improved R&R procedure resulted in better surgical success for convergence insufficiency-type X(T) [40▪]. This improved R&R procedure used an MResect based on the near deviation with the LRecess based on the distance exodeviation. This procedure was then compared with a unilateral MResect as well as a bilateral MResect and found that, although all surgical procedures reduced the near-distance differences, the improved R&R procedure had better ocular alignment at 6-months follow-up.

Surgical management of X(T) has been known to result in a high rate of undercorrections and overcorrections. With a reported incidence of 1.5–27%, consecutive esotropia may result in diplopia, reduction in stereovision and development of amblyopia [41▪▪]. Consecutive esotropia has recently been shown to occur in higher rates in patients with the following predisposing factors: divergence excess-type X(T), BLRecess, amblyopia, younger age at diagnosis and surgery, shorter duration from onset to surgery and overcorrection of at least 20 prism diopters at postoperative day 1 [42▪▪]. With patients with a long-term surgical follow-up of 10 years it was found that an increased risk of poor outcomes requiring reoperations occurred with patients with anisometropia, lateral incomitance and immediate postoperative undercorrections [43]. However, in a study of 150 consecutive patients, it was found that surgery had the highest success rate for treatment of X(T) when it was combined with preoperative orthoptic therapy/occlusion therapy in comparison with other treatments for X(T) including observation, orthoptic/occlusion therapy alone and surgery alone [44]. It may be the combination of orthoptic therapy with surgery that better addresses the neural-ocular communication needed to maintain ocular alignment than surgery alone.

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CONCLUSION

The management of intermittent exotropia continues to be controversial as the evidence of efficacy of the various treatments remains unclear [41▪▪,45▪]. Surgical treatment of childhood X(T) is associated with high recurrence rates and frequent overcorrection. Although nonsurgical therapeutic options appear less effective in improving the angle of deviation, they are rarely associated with adverse outcomes. The natural history of X(T) has not been well studied and although many cases remain stable, some cases resolve without surgery. Further rigorous studies on X(T) are indicated and there is need for standardization within these studies including parameters for measurements, stringent motor and sensory criteria in the assessment of success as well as a minimum long-term follow-up to improve the comparability and yield more information on the most effective treatments for these patients.

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Acknowledgements

None.

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Financial support and sponsorship

None.

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Conflicts of interest

There are no conflicts of interest.

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REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest
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REFERENCES

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This article from the Pediatric Eye Disease Investigator Group (PEDIG) is the first large prospective randomized study attempting to differentiate if part-time patching is a reasonable treatment approach for X(T).

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This prospective case series showed that botulinum toxin may be a promising treatment or alternative option when injected into the lateral rectus muscles in progressive X(T).

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This article factored in parental concerns, independent of patient's clinical severity, in the decision to undergoing strabismus surgery.

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This retrospective study shows that unilateral LRecess is equally effective to R&R for moderate angle X(T) over a 2-year follow-up.

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Keywords:

botulinum toxin; exodeviation; intermittent exotropia; lateral rectus recession; orthoptics

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