- 1 Disease Entity
- 1.1 Disease
- 1.2 Etiology
- 1.3 Clinical Characteristics
- 1.4 Natural History
- 2 Diagnosis
- 3 Management
- 3.1 Medical therapy
- 3.2 Surgery
- 3.3 Surgical follow up
- 3.4 Prognosis
- 4 Additional Resources
- 5 References
Exodeviations (from Greek εξοτρὀπια, εξο "exo" meaning "to exit" or "move out of”) or divergent squint is primarily a neurologic dysfunction, occurring as a result of certain obstacles to development or maintenance of binocular vision and/or defective action of the medial rectus muscles. Small exophorias are found in high frequency in the normal population and 60-70% of normal newborn infants have a transient exodeviation that resolves by 4-6 months of age. Intermittent exotropia is an exodeviation intermittently controlled by fusional mechanisms. Unlike a pure phoria, intermittent exotropia spontaneously breaks down into a manifest exotropia.
Exodeviations are much more common in a latent or intermittent form than are esodeviations. Intermittent exotropia comprises about 75-90% of the cases of exotropia and is usually preceded by a stage of exophoria. It affects about 1% of the general population. Exodeviations occur more commonly in the Middle East, subequatorial Africa and East Asia than in the United States. Jenkins made the interesting observation that the nearer a country is to the equator the higher the prevalence of exodeviations. 
Innervational Factors and Mechanical Factors
Duane championed the view that exodeviations are caused by an innervational imbalance that upsets the reciprocal relationship between active convergence and divergence mechanisms. Bielschowsky questioned Duane’s claim that the majority of exodeviations are based on hyperactive tonic divergence. This abnormal position is determined by anatomic and mechanical factors such as orientation, shape and size of the orbits, size and shape of globes, volume and viscosity of reterobulbar tissue, functioning of the eye muscles as determined by their insertion, length, elasticity anatomical and structural arrangement and condition of fascias and ligaments of the orbits. Most current theories on the etiology of exodeviations combine the ideas of Duane and Bielchowsky and are of the concept that exodeviations are caused by combination of mechanical and innervational factors.
Neuroanatomic substrates, including the area of the tegmentum of the brainstem in humans and divergence burst cells in the area of the mesencephalic reticular formation have been suggested as possible sites of a divergence center.It has been proposed that innervational imbalance in these centers is a trigger to exodeviation. Recent studies have also shown that binocular misalignment of the eyes may be secondary to extraocular muscle pulley position. A muscle pulley consists of a ring or sleeve of collagen, elastin and smooth muscle that encircles the extraocular muscles and is coupled to the orbital wall and other connective tissue structures by similar tissues. Tendons and muscles travel through pulleys by sliding inside thin collagenous sheaths that telescope within the pulley sleeves. 
Role of defective Fusion
Manifest exodeviation or exotropia are fortunately rare due to good fusional convergence reserves. In 1903, Worth developed a theory that the essential cause of exotropia is a defect of the fusion faculty and indeed is a congenital total absence of the fusion faculty. He stated that when the fusion faculty is inadequate the eyes are in a state of unstable equilibrium, ready to deviate either inwards or outwards on slight provocation.
Role of AC/A Ratio
The possibility that a high accommodation convergence to accommodation (AC/A) ratio could have a role in intermittent exotropia has been discussed at length by Cooper and Medow.These authors concluded that the AC/A ratio is either normal or just slightly higher than normal in patients who have intermittent exotropia. Kushner in 1988 found that approximately 60% patients with true divergence excess had a high AC/A ratio, and 40% had a normal AC/A ratio.
Theory of Hemiretinal Suppression
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.
Role of Refractive Errors
In addition to interplay between the convergence and divergence mechanisms, refractive errors may further modify the innervational pattern that influences the position of the eyes. In a patient with uncorrected myopia, less than normal accommodative effort is required during near vision thus causing decreased accommodative convergence. According to Donders, this constant under-stimulation of convergence may cause an exodeviation to develop. Similarly in patients with a high degree of uncorrected hypermetropia no effort is made to overcome the refractive error by an accommodative effort and clear vision is unattainable. This may lead to development of an exodeviation on the basis of an under stimulated and thus underactive convergence mechanism that causes the AC/A ratio to remain low. Thus refractive errors, through their effect on accommodation, are undoubtedly one of the prime causes of misalignment of the eyes. Unequal clarity of retinal images may present an obstacle to fusion, facilitate suppression and therefore contribute to the pathogenesis of exotropia.
Genetics and Risk factors
Although heredity appears to play a role in exodeviations, the etiology of this disorder is thought to be multifactorial. A positive family history is often noted.Children born with craniofacial anomalies and those with neurologic defects are more likely to exhibit exotropia. Maternal smoking during pregnancy and low birth weight are significant and independent risk factors for the development of horizontal deviations.
Age of Onset
The onset of the majority of exodeviations is shortly after birth. In a series of 472 patients with intermittent exotropia, the deviation was present at birth in 204 individuals and appeared in 16 individuals at 6 months of age and in 72 individuals between 6-12 months of age. Exotropia developed after 5 years of age in only 24 patients. With rare exceptions, exodeviatons begins as an exophoria that may deteriorate into intermittent and then constant exotropia as suppression develops. Suppression is believed to be the key that unlocks the fusion mechanisms.
Most studies describe a preponderance of female patients in exotropia.
The natural history of intermittent exotropia remains unclear due to lack of well controlled longitudinal prospective studies of untreated intermittent exotropia. In some cases, an exophoria progresses to an intermittent exotropia that eventually becomes constant. Such deviation usually occurs first at distance and later at near fixation. This process may be influenced by decreased tonic convergence with increasing age, the development of suppression, loss of accommodative power and increasing divergence of the orbit with advancing age.Nevertheless, not all intermittent exotropias are progressive. In some cases, the deviation may remain stable for many years, and in a few cases, it may even improve. Thus the patient should be followed over time to determine whether their exotropia is stable or deteriorating. Von Noorden found that 75% of 51 untreated patients showed progression over an average follow up period of 3.5 years while 9% did not change, and 16% improved.
Intermittent exotropia is the most common type of exodeviation and is usually first observed by the parents in early childhood as a spontaneous drifting out of one eye mostly when the child is tired, sick or daydreaming. Adult patients may manifest exodeviation after consuming alcoholic beverages or taking sedatives.
Assessing Control of Intermittent Exotropia
The assessment of control of intermittent exotropia is essential to obtain a baseline evaluation as well as to monitor deterioration and progression of intermittent exotropia.
- Home Control: The parents may be told to keep a chart noting the control of deviation at home in terms of the percentage of waking hours the manifest deviation is noted at home.
- Office Control:
- Good Control: Patient “breaks” only after cover testing and resumes fusion rapidly without need for a blink or refixation.
- Fair Control: Patient blinks or refixates to control the deviation after disruption with cover testing.
- Poor Control: Patient who breaks spontaneously without any form of fusion disruption, or who does not spontaneously regain alignment despite blink or refixation.
Distance Stereoacuity: Distance stereoacuity provides an objective assessment of both control of the deviation and deterioration of fusion. Normal distance stereoacuity usually indicates good control with little or no suppression.
Near Stereoacuity: In a study it was shown that near stereoacuity does not correlate well with the degree of control in intermittent exotropia and that performance in this test is only minimally affected by surgery. However, near stereoacuity can be used as a marker for deterioration of the disease; if near stereoacuity is deteriorating, it is likely that the patient’s control is not sufficient to prevent amblyopia from developing.
Measuring the Angle of Deviation
Due to the variable angle of deviation, measurement in a patient with intermittent exotropia can be difficult by routine alternate cover prism testing. A prolonged alternate cover testing should be used in patients with intermittent exotropia to suspend tonic fusional convergence. If after prolonged alternate cover testing, there is significant angle variability or a significant distance/near discrepancy, then a patch test is indicated. Monocular occlusion should be used before using a +3.00 D lenses to measure near deviation, to avoid misdiagnosing a high AC/A ratio. The + 3.00 lenses suspend normal accommodative convergence, whereas monocular occlusion relaxes fusional convergence mechanisms.
- Patch Test - The patch test is used to control the tonic fusional convergence to differentiate pseudo-divergence excess from true divergence excess and to reduce the angle variability. Contrary to the earlier practice of patching one eye for 24 hrs, it is now found that patching the eye for 30 minutes is sufficient to suspend the tonic fusional convergence and thus reveal the actual amount of deviation.
- +3.0 D near add test (lens gradient method) - This test has been devised to distinguish individuals who have pseudo-divergence excess from a high AC/A ratio rather than true divergence excess. This test uses the lens gradient method to measure the AC/A ratio. Patients with high AC/A ratio often continue to have a distance-near disparity post-operatively, and may require bifocal spectacles after surgery for a consecutive esotropia at near. This test should be used in patients who have a distance deviation or 10 prism diopters or more greater than near deviation after the patch test. After the patch test, while still dissociated, one should remeasure the deviation at near with a +3.0 add over each eye. If the exodeviation at near increases by 20 prism diopters or more the diagnosis, of psuedo-divergence excess with high AC/A ratio is made.
- Far distance measurement - Measuring the deviation by fixating on a distant object reduces measurement variability and helps uncover the full deviation by reducing near convergence. Combining the patch test and far distance measurement can greatly reduce under-corrections and has improved the overall result. In a prospective randomized trial, 86% of patients who underwent surgery for the largest angle had a satisfactory outcome, compared with 62% who were operated on for the standard 6 meter distance deviation. A far distance measurement is considered to be ¼ mile or further.
Patients with intermittent exotropia rarely complain of symptoms. The surprising absence of symptoms is related to a well-developed suppression mechanism. The various symptoms a patient may report in intermittent exotropia are as follows:
- Transient Diplopia: Some patients report occasional transient horizontal diplopia, others will have a vague sense of discomfort or blurred vision when their eyes are deviated.
- Asthenopic symptoms may occur in initial phases when eyes are deviated momentarily. Some patients may notice symptoms like eyestrain, blurring, headache and difficulty with prolonged periods of reading. However, these patients may quickly become asymptomatic due to the development of sensory adaptation.
- Micropsia: Some patients may complain of micropsia that may occur due to the use of accommodative convergence to control the exodeviation.
- Diplophotophobia One symptom that deserves a special comment is closure of one eye in bright sunlight. The theorized cause is that bright sunlight dazzles the retina so that fusion is disrupted, causing the deviation to become manifest.Thus one eye is closed in order to avoid diplopia and confusion.
Intermittent exotropia has been divided into four groups according to the classification system proposed by Burian. This system is based upon the concept of fusional convergence and divergence and relies on measurements of the distance and near deviations.
- Basic Intermittent exotropia: is present when the measured deviation at distance is within 10 prism diopters of the near deviation. Patients with basic type intermittent exotropia have a normal tonic fusional convergence, accommodative convergence (normal AC/A ratio) and proximal convergence.
- Divergence Excess: is present when the distance deviation is 10 prism diopters greater than the near deviation. Kushner found that approximately 60% patients with true divergence excess had a high AC/A ratio, and 40% had a normal AC/A ratio. The group with a high AC/A ratio is prone to postoperative over correction at near if the distance measure is used as a surgical target angle.
- Convergence Insufficiency: is present when the near deviation is 10 prism diopters greater than the distance deviation.
- Simulated or Pseudo-divergence Excess: is present when the patient has a larger exotropia at distance than near but the near deviation increases within 10 prism diopters of the distance deviation after 30-60 min. of monocular occlusion. This occurs because patients with pseudo-divergence excess have increased tonic fusional convergence at near. The prolonged monocular occlusion dissipates tonic fusional convergence thereby disclosing the full latent deviation.
Kushner has attributed disparity between distance and near deviation in intermittent exotropia to proximal vergence after effects and to alterations in AC/A ratio. The term tenacious proximal fusion has been used to describe the fusional after effects that explain the distance near disparity in patients previously classified as pseudo-divergence excess type. These patients with reduced angle of strabismus at near appear to have a slow to dissipate proximal fusion mechanism that prevents them from manifesting their true near deviation during a brief cover test. Although Kushner’s system is complex it can be used to guide patient evaluation and management.
Similar to Burian’s classification system, distance and near measurements must be obtained. In addition, if a disparity exists between the distance and the near measurement, the AC/A ratio is obtained using the lens gradient method. This is done by using a –2.0 D lens at distance, or by using a +3.0 D lens at near after fusion has been suspended by using 60 minutes of occlusion.
Although nonsurgical management for intermittent exotropia is not very effective, it may be preferred in patients with small deviations with excellent control, very young patients in whom surgical overcorrection can lead to amblyopia or loss of bifoveal fixation, and in patients who otherwise cannot be taken to surgery for medical reasons. Additionally, patients with a high AC/A ratio may be responsive to non-surgical methods. Management options include the following:
- Correction of Refractive Errors: Anisometropia, astigmatism, myopia and even hyperopia can impair fusion and result in a manifest deviation. A trial of corrective lenses based on cycloplegic refraction is often warranted. Myopes, in particular, will often improve control of their intermittent exotropia and may become phoric if given corrective lenses.
- Overcorrecting minus lens therapy: This technique is based on the principle that stimulating accommodative convergence can reduce an exodeviation. This is particularly useful in patients who have a high AC/A ratio. Overcorrection with minus lenses may improve the quality of fusion and occasionally may even decrease the angle of deviation so that surgery may be deferred.
- Part time occlusion: This technique has found some use in very young children. It is a passive anti-suppression technique as opposed to the active techniques involving diplopia awareness. Part time patching of the non-deviating eye may convert an intermittent exotropia to a phoria by treating supression and amblyopia. Although the benefit is usually temporary, occlusion can be used to postpone surgical intervention in responsive patients. Alternate occlusion may be used in patients with equal fixation preferences. Initially the results are evaluated after 4 months of occlusion. If the angle of deviation is decreased the occlusion should be continued and assessment made every 4 months until no further change occurs. In case there is no improvement for 4 months, it is discontinued.
- Prism therapy: Some strabismologists recommend a use of base-in prisms to enforce bifoveal stimulation. Prisms are rarely a long-term solution in patients with intermittent exotropia, but can be used to improve fusional control, or as a temporizing measure, either pre or postoperatively.
- Orthoptics: Knapp summarized the opinion of most strabismogists by stating that orthoptics should not be used as a substitute for surgery but rather as a supplement. The aim is to make the patient aware of manifest deviation and to improve the patient’s control over it. Active anti-suppression and diplopia awareness techniques can be used in cases with suppression. Convergence exercises such as pencil push-us or computer orthoptics may be helpful in patients who have a remote near point of convergence, or in whom poor fusional convergence amplitudes are demonstrated.
Indications for surgery
As with any strabismus, the indications for surgery include preservation or restoration of binocular function, prevention of diplopia, and cosmesis. In intermittent exotropia, one of the important indications for therapeutic intervention is an increasing tropia phase, since this indicates deteriorating fusional control. If the frequency or duration of the tropic phase increases, this indicates diminished fusional control and the potential for losing binocular function. Progression should be monitored by documenting the size of the deviation, the duration of manifest deviation and the ease of regaining fusion after dissociation from the cover-uncover test. Deteriorating fusional control is an indication for surgery.
Signs of Progression of Intermittent Exotropia
- Gradual loss of fusional control evidenced by the increasing frequency of the manifest phase of exodevition
- Development of secondary convergence insufficiency
- Increase in size of the basic deviation
- Development of suppression as indicated by absence of diplopia during manifest phase
- Decrease of Stereoacuity
Timing for Surgery
There is a controversy about the management of children less than 4 years of age because, in contrast to infantile esotropia, most of these children have intermittent fusion and excellent stereopsis. Knapp and many other workers advocated early surgical intervention to prevent development of sensory changes that may prove intractable later. However they do caution that in visually immature children a slight undercorrection should be attempted to prevent occurrence of monofixation syndrome from consecutive esotropia. Jampolsky advocates delayed surgery, citing advantages like accurate diagnosis and quantification of the amount of deviation and to avoid consecutive esotropia and development of amblyopia. Although one study reported better outcomes in children who were under the age of 4 years,most studies have failed to show that age at time of surgery makes any difference in outcome. Thus it is now believed that surgery in this age group is reserved for patients in whom rapid loss of control is documented. In the interim, minus lenses or part time patching may be used as non-surgical methods and these patients followed closely for signs of progression.
Type of Surgery
Lateral Rectus Recession: Bilateral lateral rectus recession is the preferred surgical modality for patients with true divergence excess. In patients with small deviations up to 16 prism diopters, large unilateral lateral rectus recessions on the non-dominant eye may be effective.Surgery may be performed with or without the use of adjustable sutures.
Recession-Resection Procedure: This procedure involves lateral rectus recession with medial rectus resection. A prospective randomized study revealed that recess-resect procedure to be more successful in cases of basic exodeviation as compared to bilateral lateral rectus recession. In patients with unilateral amblyopic, the surgeon often chooses unilateral recess-resect surgery thereby avoiding surgery on the eye with good vision. Large angle exotropia of more than 50 prism diopters usually require bilateral lateral rectus recessions combined with resection of one or more medial rectus muscles, even in the presence of amblyopia.
Medial Rectus Resection: Bilateral medial rectus resections are thought to be useful for the treatment of the convergence insufficiency type of intermittent exotropia because of the increased effect of this surgery at near.
Lateral Incomitance: Lateral incomitance is a difference in amount of deviation on lateral gaze. Moore has shown that patients with preoperative lateral incomitance are much more likely to be overcorrected with surgery. For this reason, some surgeons have suggested reducing the amount of recession in patients with lateral incomitance, especially if the deviation in lateral gaze is 50% less than the deviation in primary position.
Goal of Surgery
The goal of surgery for intermittent exotropia is to restore alignment and to preserve or restore binocular function. 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 prism diopters.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 cause amblyopia and loss of binocularity. In older children and adults who develop intermittent exotropia, 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 undercorrection, but will have symptomatic diplopia when overcorrected.
A-and V-patterns: Oblique overaction
Intermittent exotropia may be associated with inferior or superior oblique overaction and thus A- and V-pattern. For inferior oblique overaction with a significant V-pattern (15 or more prism diopters), the inferior oblique muscles may be weakened at the time of horizontal surgery. If significant superior oblique overaction and an A-pattern is present, one may consider an infra placement of the lateral rectus muscles or a superior oblique weakening procedure at the time or horizontal muscle surgery. It is generally not required to alter the amount of horizontal surgery when simultaneous oblique surgery is performed. Small vertical deviations associated with intermittent exotropia should be ignored since these vertical phorias less than 8 prism diopters usually disappear after surgery. Another point of caution is that, with longstanding exotropia, a pseudo A and/or V pattern may be noticed due to a tight lateral rectus muscle which causes slippage of the globe under the tight muscles in extreme vertical gazes. This upshoot and downshoot of the eyeball will mostly be corrected by recessing the tight lateral rectus and does not require any surgery on the oblique muscles.
Surgical follow up
The post-operative treatment depends on the position of the eyes postoperatively. The eyes may be in orthophoric, may show residual exodeviation (undercorrection) or may show consecutive esodeviation (overcorrection).
Orthophoria: Immediately after surgery, a small consecutive esotropia of up to 8 prism diopters is desirable in children. There is a tendency of the eyes to diverge postoperatively, thus for long term success if postoperatively an orthophoria is noted in the early period, it may be helpful to strengthen the positive fusional convergence with orthoptic exercises in order to improve control of the newly acquired bifoveal single vision. As previously mentioned, older children and adults who develop intermittent exotropia usually present with diplopia and in these patients orthotropia in the immediate postoperative period may be desirable.
Consecutive esotropia (Overcorrection): A small consecutive esotropia of up to 8 prism diopters is a desirable postoperative result in children up to 6 years of age. Even a moderate consecutive esotroia of up to 20 prism diopters may resolve without further surgery. The parents and or the patients should always be warned before the surgery that postoperative diplopia might occur so that they are not surprised. Nonsurgical management of overcorrection should be tried for at least a month rather than re-operating because of the high likelihood of spontaneous resolution. An unusually large overcorrection with gross limitation of ocular motility noted on the first postoperative day is possibly due to lost or slipped lateral rectus muscle. Such cases should be taken up for surgery as soon as possible.
Children: In visually immature age group even a small esotropia is associated with a danger of developing amblyopia thus these patients require special care. Any refractive error, especially hyperopia, should be fully corrected. Bifocals may be prescribed if the deviation is greater at near. In children under 4 years of age, part-time alternate patching of each eye helps prevent amblyopia and may facilitate straightening of the eyes. If a residual esotropia persists past 3 weeks, then the patient should be treated with prism glasses to neutralize the esotropia. Prescribe just enough power to allow fusion, but leave a small residual esophoria to encourage divergence. If after 6-8 weeks the esotropia persists, then a reoperation should be considered. In case of a limited adduction or lateral incomitance, advancement of the lateral rectus is indicated. Otherwise, bimedial recession is usually the procedure of choice for a consecutive esotropia, especially if the esotropia is greater at near.
Adults: In patients in the visually mature age group with an overcorrection of more than 20 prism diopters, nonsurgical measures may be tried till 6-8 weeks after which re-operation should be planned if the deviation persists.
Residual Exotropia (Undercorrection):
Small residual exotropia (<15 Prism diopters): should be primarily managed by non-surgical measures. Any refractive error especially myopia should be fully corrected. In hypermetropic or emmetropic patients, cycloplegics may be instilled twice a day to stimulate accommodative convergence. Orthoptic exercises in the form of antisuppression exercises and fusional convergence exercises should be continued till the proper alignment is achieved. Prism therapy in the form of base in prisms may be tried in some patient.
Large residual exotropia (>15 Prism diopters): Patients with a residual exotropia over 15 prism diopters in the first postoperative week will probably not improve and many will require additional surgery. It is better to wait 8-12 weeks before re-operating on the residual exotropia. If the primary surgery was bilateral lateral rectus recession of 6 mm or less, re-recession of the lateral rectus may be performed. If the primary recession was greater than 6 mm, then bilateral medial rectus resections with a conservative approach are preferred, as overcorrections are common after resecting against a large recession.
Due to lack of a standard definition for a successful outcome, variability in classification systems, multiple treatment approaches, and a paucity of long-term data it is difficult to determine the true outcome of currently available treatments for intermittent exotropia. The success rate of intermittent exotropia is dependent on the length of follow-up. The longer the follow up, the higher the incidence of undercorrection. Short-term studies with 6 months to 1 year follow-up report a success rate of approximately 80%, whereas studies with 2-5 year follow-up have shown a 50-60% success rate with one surgery. In recent studies, the reported success rate in all types of intermittent exotropia have been about 60-70%. In most of these reports, success was defined as alignment within 10 prism diopters of orthophoria, and mean follow-up was no greater than 4.5 years. Kushner studied surgical outcomes relative to classification of intermittent exotropia, surgical technique and surgical dosage.
The conclusions drawn from his data are:
- A high AC/A is an indicator of a poor surgical prognosis and most of these patients have a consecutive esotropia at near.
- Tenacious proximal fusion is an indicator of a good surgical prognosis.
If a patient shows an increase in the size of distance deviation when measured after monocular patching or when viewing a far distance target, the surgery should be performed for the largest deviation that can be documented consistently.
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