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Articles: Original Article

The Clinical Course of Intermittent Exotropia

RUTSTEIN, ROBERT P. OD, MS, FAAO; CORLISS, and DAVID A. OD, PhD

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Author Information

School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama

Received October 17, 2002;

revision received May 26, 2003.

Robert P. Rutstein

College of Optometry

University of Alabama at Birmingham

1716 University Blvd.

Birmingham, AL 35294-0010

e-mail: rrutstein@icare.opt.uab.edu

ACKNOWLEDGMENTS Presented, in part, at the annual meeting of the American Academy of Optometry, San Diego, California, December 2002.

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Abstract

Purpose. To report the clinical course for patients with intermittent exotropia.

Methods. The clinical records of patients diagnosed with intermittent exotropia from 1983 to 1991 who had at least 4 years of follow-up were reviewed. All patients with neurological or medical abnormalities, developmental delays, ocular disease, or having strabismus surgery during the follow-up period were excluded.

Results. Of the 468 records reviewed, 73 met the inclusion criteria. Forty-four patients were female, and 29 were male. Fifty-two patients had basic intermittent exotropia, 11 patients had divergence excess intermittent exotropia, and 10 patients had convergence insufficiency intermittent exotropia. The mean age at initial visit was 20 years (range, 1 to 63 years). The mean follow-up was 10 years (range, 4 to 23 years). Four patients had amblyopia of 20/30 or worse, nine patients had a vertical deviation in the primary position, and 10 patients had undergone extraocular muscle surgery before coming to our clinic. Sixty patients received some form of treatment during follow-up. The mean stereoacuity at the initial and final visits were 59 and 70 s arc, respectively. The initial mean spherical equivalent refraction was −0.48 D and increased to −1.15 D at the end of the study. The mean exodeviation changed from 17.2 Δ at distance and 17.6 Δ at near at the initial visit to 13.7 Δ at distance and 13.5 Δ at near at the final visit. At the initial visit, 63 patients were exotropic and 10 patients were either heterophoric or orthophoric at distance, whereas, 60 patients were exotropic and 13 patients were either heterophoric or orthophoric at near. At the final visit, 37 patients were exotropic and 36 patients were either heterophoric or orthophoric at distance whereas 33 patients were exotropic and 39 were either heterophoric or orthophoric at near. One patient was esotropic at near at the last visit. Changes in the size and quality of the exodeviation, although statistically significant (p < 0.001), were not associated with any specific treatment regimen or with longer periods of follow-up. Measurements exhibited a regression toward the mean.

Conclusions. Intermittent exotropia improved for many patients quantitatively and qualitatively over time. That the improvement was unrelated to any treatment and length of follow-up suggests that the changes at least quantitatively are not associated with any physiologic process and may be due, in part, to regression toward the mean.

Intermittent exotropia is an ocular deviation that at times is completely controlled by positive fusional vergence and presents as an exophoria and at other times is not controlled by positive fusional vergence and presents as an exotropia. Exophoria supposedly precedes the development of the intermittent exotropia, but this is probably not always the case. It is a relatively common form of strabismus occurring in about 25% of all strabismic cases and in 1% of the general population. 1–3 Its age of onset varies but is often between 6 months and 4 years. 4

The clinical course of intermittent exotropia is unclear. It has been reported to be a progressive disorder. 5 Progression or deterioration over time may take different forms. The intermittent exotropia may increase in size, may spread to another fixation distance, may become more frequent, or may become constant with loss of binocular vision and stereopsis. Some of the factors leading to progression include decreased tonic convergence, decreased accommodation, suppression, and increased separation of the orbits with age.

We have noted that some patients with intermittent exotropia do not progress over time and may even improve. There are patients who manifest intermittent exotropia in early childhood and are exophoric as adults. Hiles and associates 6 followed 48 patients with intermittent exotropia for an average period of 11.7 years. During the follow-up period, no patient received strabismus surgery. As many as 80% received some vision therapy. The average deviation at distance decreased from 23 to 18 Δ, and the average deviation at near decreased from 11 to 8 Δ. Forty patients (83%) remained within 10 Δ of their original distance measurements at the end of the study. In addition, 31 of the 48 patients (64%) ceased to manifest exotropia and were heterophoric at the last visit. von Noorden 7 followed 51 patients with intermittent exotropia who were not treated for an average of 3.5 years. In 25% of the cases, the intermittent exotropia either remained unchanged or improved. The purpose of this study was to report the clinical course of patients with intermittent exotropia examined in our clinic.

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METHODS

After approval from our institutional review board, the clinical records of all patients diagnosed with intermittent exotropia for distance and/or near at the University of Alabama at Birmingham School of Optometry Binocular Vision Clinic from 1983 to 1991 were reviewed. All patients had to have a follow-up for ≥4 years. Records of patients with neurological or medical abnormalities, developmental delays, ocular disease, or having had strabismus surgery during the follow-up period were excluded. Information retrieved from the records included patient gender, age at initial visit, number of visits, length of follow-up, presence of amblyopia, presence of a vertical deviation in primary position, history of strabismus surgery before the initial visit, whether or not other treatment was given during follow-up, and the type of treatment, the magnitude, and type of ocular deviation at distance and near, the stereoacuity, and the refractive error at the initial and final visits.

For this study, amblyopia was defined as best-corrected visual acuity of 20/30 or poorer in the deviating eye. The magnitude of the deviation was determined with the alternate prism cover test at distance and near utilizing accommodative targets and with the patient wearing their refractive correction. Stereopsis was determined at near using either the Titmus or Randot stereotest. The mean spherical equivalent for each patient was calculated and used as the refractive error. All clinical measurements were taken either by one of the authors (RPR), optometry clinical faculty experienced in binocular vision anomalies, or senior optometry interns.

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RESULTS

Of 468 records reviewed, the records of 73 patients, 44 females and 29 males, were used in the study. Table 1 characterizes subject age distribution and follow-up. The 73 patients, ranging in age from 1 to 63 years at their first visits, were seen a total of 572 times. The time between the first and last recorded visits ranged from 4 to 23 years, with an average of 10 years. The elapsed time between successive visits averaged about 1 year.

Table 1
Table 1
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The type of intermittent exotropia was classified according to its magnitude at distance and near. Fifty-two patients (71%) had a basic exodeviation with the deviation at both distances being within 10 Δ; 11 patients (15%) had a divergence excess exodeviation with the deviation at distance exceeding the deviation at near by 10 Δ or more; and 10 patients (14%) had a convergence insufficiency exodeviation with the deviation at near exceeding the deviation at distance by 10 Δ or more.

Four patients (5%) had amblyopia of 20/30 or poorer (range, 20/30 to 20/70). Three of these patients had anisometropia of 1 D or more with the largest refractive error occurring in the deviating eye. The other amblyopic patient had low myopic refractive error in each eye. The low number of patients with amblyopia is consistent with other studies. 8, 9

Nine patients (12%) manifested a vertical deviation in primary position in addition to the intermittent exotropia. One patient had a dissociated vertical deviation with LN. She had strabismus surgery at 1 year for infantile esotropia. At the first visit in our clinic when she was 8 years old, she manifested intermittent exotropia at distance and near and had 80 s arc stereopsis.

Ten patients (14%) had undergone strabismus surgery before being examined in our clinic. Two patients had surgery for esotropia and subsequently developed intermittent exotropia. Eight patients had recurring intermittent exotropia.

Sixty patients (82%) had nonsurgical treatment prescribed at some time during the follow-up period. Thirty-six patients (49%) had vision therapy, 25 (34%) were prescribed prism, and 20 (27%) were prescribed over-minus lenses. Two patients (3%) received occlusion therapy for amblyopia. Twenty-four patients (33%) received more than one type of treatment. Thirteen patients (18%) received no specific treatment for the intermittent exotropia during the follow-up period.

The mean stereoacuities at the first and final visits were 59 and 70 s arc. At the initial visit, 50 of the 52 patients tested had measurable stereopsis compared with 44 of the 46 patients tested at the final visit. Only one patient had no measurable stereopsis at both the first and last visits. Another patient who had stereopsis initially did not have stereopsis at the last visit. For both patients, the magnitude of the exodeviation decreased by more than 10 Δ at one fixation distance.

The mean spherical equivalent refraction changed from −0.48 to −1.15 D. At the first visit, 35 patients had a spherical equivalent refraction ranging from −0.50 to +0.50 D compared with 20 patients at the last visit. The number of patients having >1 D anisometropia either in the spherical or astigmatic components of their refraction was similar at both visits.

Table 2 shows the mean magnitudes of the exodeviations, the differences between the mean magnitudes at the first and the last visits, and the dependent t-test results. Overall, the intermittent exotropia became smaller, the changes being significantly different. The difference in magnitudes of the distance and near deviations represent changes of 20% and 24%, respectively. The exodeviation decreased by 5 Δ or more for 28 patients at distance and for 33 patients at near. It stayed the same or decreased by <5 Δ for 21 and 26 patients at distance and near, respectively. For the remaining patients, the deviation increased. However, the increase was larger than 5 Δ at either distance or near for only six patients.

Table 2
Table 2
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The effect of treatment regimen and length of follow-up on the changes in the exodeviation were analyzed. As shown by repeated-measures analysis of variance, there was no significant difference (F = 0.0002, p = 0.99) in the magnitude of the changes in the exodeviation at the first and final visits for patients who were treated at some point during the follow-up period (N = 60) vs. patients who were not treated (N = 13). This could be the result of poor patient compliance because the analysis is based on whether treatment was prescribed, not on the type of treatment or the amount of treatment actually done.

For the 10 patients who had strabismus surgery before being evaluated in our clinic, the effect of surgical history on the changes in the exodeviation over time was also analyzed. As shown by repeated-measures analysis of variance, surgical history had no effect on the magnitude of change in the distance deviation (F = 0.523, p = 0.472) and the near deviation (F = 0.825, p = 0.367).

Fig. 1 shows that the exodeviation at distance had a tendency to decrease with increasing patient age. Despite the high degree of scatter, the relation is significant (r = −0.168, p < 0.001), although age explains little of the variance.

Figure 1
Figure 1
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Fig. 2 illustrates the change in magnitude between the first and last visits as a function of time between those visits. There is no significant relation between these two variables. Fig. 3 shows that the change in the magnitude of the deviation between the first and last visit is also independent of the age at which the patient was first evaluated in our clinic. In addition, Fig. 4 illustrates the change in magnitude of the distance deviation at each visit from the magnitude at the first visit vs. the time between the first and each successive visit. Again, there is no significant relation.

Figure 2
Figure 2
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Figure 3
Figure 3
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Figure 4
Figure 4
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The observed differences in the magnitude of the exodeviation are possibly due, at least in part, to a measurement effect. In particular, where there are functions in any kind of physiologic measurement due either to physiologic variability or measurement error, there may exist the phenomenon of regression toward the mean. 10 This means that if at one visit the magnitude is higher than the mean, then at the next visit there is good likelihood that the magnitude will be smaller than the first measure. Conversely, if the initial measurement is low at one visit, it may be higher at the next.

Fig. 5 demonstrates the existence of this measurement phenomenon in our data. Fig. 5 shows the probability of an increase, a decrease, and no change in the magnitude of the exodeviation from one visit to the next as a function of the magnitude of the deviation at a particular visit. It is clear that as the magnitude of the exodeviation increases, the probability of measuring a smaller value at the next visit increases, whereas the probabilities of measuring a smaller value or no change decreases. The opposite is true at low values of the deviation.

Figure 5
Figure 5
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Concomitant with but independent of the magnitude of the deviation, the type of deviation is classified as either an intermittent exotropia or phoria. Initially, 63 patients (86%) were exotropic and 10 patients (14%) were either heterophoric or orthophoric at distance, whereas 60 patients (82%) were exotropic and 13 (18%) were either heterophoric or orthophoric at near. Fifty patients (68%) manifested intermittent exotropia at both distance and near. At the last visit, 37 patients (51%) were exotropic and 36 (49%) were either heterophoric or orthophoric at distance, whereas 33 (45%) were exotropic and 39 (53%) were either heterophoric or orthophoric at near. Twenty-eight patients (38%) manifested intermittent exotropia at both distance and near. One patient manifested intermittent esotropia at near during the last visit and was prescribed bifocals.

Table 3 shows cross tabulations of the exodeviation types at the first and last visits. All the changes are statistically significant (McNemar χ2 = 8.4, p = 0.001 for distance, and McNemar χ2 = 14.6, p < 0.001 for near). Fig. 6 shows the mean magnitudes of the distance deviations associated with these quality changes. There are no changes from exophoria to intermittent exotropia. Exotropias <20 Δ had a higher incidence of converting to exophoria than did exotropias exceeding 20 Δ.

Table 3
Table 3
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Figure 6
Figure 6
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DISCUSSION

The results of this retrospective study indicate that intermittent exotropia does not progress with advancing age for many patients and may even improve. For our patients, the first and last stereopsis measurements were similar; the magnitude of the deviation became smaller by an average of 3.5 Δ at distance and 4.1 Δ at near, and for 36% of the patients, the intermittent exotropia converted either to exophoria or orthophoria at the last visit.

These findings are in agreement with those of Hiles and associates 6 and Fournier and associates 11 (Table 4). Unlike the earlier retrospective studies, the present study was not limited to children and also included patients who had undergone strabismus surgery before being examined in our facility. In addition, most of our patients (71%) had a basic intermittent exotropia, whereas most patients in the earlier studies had a divergence excess intermittent exotropia.

Table 4
Table 4
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If there is a physiologic process that caused the overall improvement, one might expect that it would be affected by treatment regimen and/or length of follow-up. The intermittent exotropia would be more likely to have become smaller for patients who were treated during follow-up vs. those who were not treated. Similarly, greater decreases in the exodeviation would be more likely for patients having longer periods of follow-up vs. shorter periods of follow-up. We could, however, find no time dependency that one would expect of a physiologic process to explain the lack of progression and overall improvement of intermittent exotropia. Furthermore, the reduction in the magnitude was not related to whether patients were prescribed treatment such as vision therapy, prisms, or over-minus lenses during the follow-up period.

Fournier and associates 11 treated 35 of their 65 patients with either vision therapy, prisms, or over-minus lenses and reported that the average distance exotropia decreased from 21 Δ to 15.6 Δ, whereas for the 30 patients not receiving treatment, the magnitude remained relatively stable. Hiles and associates 6 also prescribed vision therapy for approximately 80% of their patients. Sixty patients in the present study were prescribed nonsurgical treatment such as vision therapy, over-minus lenses, and/or prism at some time during the follow-up period. Our analysis was based on whether treatment was prescribed as determined by record review rather than the actual amount of therapy that was actually done. A prospective study that carefully monitors the amount of therapy undertaken is needed to determine the efficacy of nonsurgical treatment in reducing the magnitude of intermittent exotropia.

Although the magnitude of the intermittent exotropia varied somewhat with the age of the patient, its overall reduction was unrelated to the duration of the follow-up. In part, these changes can be attributed to a statistical phenomenon known as regression toward the mean. 10 If at one visit the magnitude is higher than the mean, than at the next visit it is likely that the magnitude will be smaller than the mean. Conversely, if the first measurement is low, it is likely that it will be higher at the next visit. This is illustrated for our patients in Fig. 5. Regression toward the mean is not limited to measuring ocular deviations and has also been reported in studies monitoring intraocular pressure. 12

The findings of Hiles and associates 6 were digitized and replotted to determine whether regression toward the mean was also a factor in their study. As illustrated in Fig. 7, it is evident that as the magnitude of the deviation at the first visit increased for their patients, the probability of a decrease at the last visit also increased. It should be noted that the data of Hiles and associates 6 involved analysis comparing only the first and last patient visits, whereas our data analyzed the magnitude of the exodeviation for each successive patient visit.

Figure 7
Figure 7
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Over one-third of our patients no longer manifested intermittent exotropia and were either heterophoric or orthophoric at the last visit. For the 48 patients reported by Hiles and associates, 6 64% were heterophoric at the last visit. However, Chia and associates 13 recently reported improved control of intermittent exotropia in only 18% of their patients at distance and in only 6% of their patients at near. The magnitude of the exotropia for their patients was generally larger and averaged 36 Δ at distance and 26 Δ at near. Combining the findings of the present study with those of Hiles and associates, 6 it appears that as many as half of patients with intermittent exotropia may achieve better control over time for at least one fixation distance. This appears more likely when the exodeviation is <20 Δ (Fig. 6).

In summary, intermittent exotropia improved both quantitatively and qualitatively for many of our patients. The quantitative changes were possibly due, in part, to the effect of regression toward the mean. Intermittent exotropia may not be a progressive disorder for many patients. A long-term prospective study that carefully monitors the magnitude and quality of intermittent exotropia is needed to add to our knowledge of this type of strabismus.

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REFERENCES

1. Cooper J, Medow N. Intermittent exotropia: basic and divergence excess type. Binoc Vis Eye Muscle Surg 1993; 8: 185–222.

2. Chew E, Remaley NA, Tamboli A, Zhao J, Podgor MJ, Klebanoff M. Risk factors for esotropia and exotropia. Arch Ophthalmol 1994; 112: 1349–55.

3. Newman J, Mazow ML. Intermittent exotropia: is surgery necessary? Ophthalmic Surg 1981; 12: 199–202.

4. Rutstein RP, Daum KM. Anomalies of binocular vision: diagnosis and management. St. Louis, MO: Mosby, 1998.

5. Jampolsky A. Differential diagnostic characteristics of intermittent exotropia and true exophoria. Am Orthopt J 1954; 4: 48–55.

6. Hiles DA, Davies GT, Costenbader FD. Long-term observations on unoperated intermittent exotropia. Arch Ophthalmol 1968; 80: 436–42.

7. von Noorden, GK. Binocular vision and ocular motility: theory and management of strabismus, 5th ed. St. Louis, MO: Mosby, 1996.

8. Smith K, Kaben TJ, Orton R. Incidence of amblyopia in intermittent exotropia. Am Orthopt J 1995; 45: 90–6.

9. Dunlap EA, Gaffney RB. Surgical management of intermittent exotropia. Am Orthopt J 1963; 13: 20–33.

10. Streiner DL. Regression toward the mean: its etiology, diagnosis, and treatment. Can J Psychiatry 2001; 46: 72–6.

11. Fournier AV, Keech RV, Havertape SA. The long-term course of unoperated intermittent exotropia. Paper presentation at the annual meeting of the American Academy of Pediatric Ophthalmology and Strabismus, 2000.

12. Munger R, Dohadwala AA, Hodge WG, Jackson WB, Mintsioulis G, Damji KF. Changes in measured intraocular pressure after hyperopic photorefractive keratectomy. J Cataract Refract Surg 2001; 27: 1254–62.

13. Chia AW, Quah BL, Linley S. Progression of intermittent exotropia amongst children in Singapore. Poster presentation at the annual meeting of the American Academy of Pediatric Ophthalmology and Strabismus, 2000.

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Keywords:

intermittent exotropia; exophoria; follow-up; progression; regression toward the mean

© 2003 American Academy of Optometry

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