- Email: [email protected]
Long-term outcome of uncomplicated infantile exotropia
Long-Term Outcome of Uncomplicated Infantile Exotropia David G. Hunter, MD, PhD,a,b Jane Barrett Kelly, MEd, MD,a Angela N. Buffenn, MD, MPH,a and Forrest J. Ellis, MDc Purpose: The term congenital exotropia (XT) is typically reserved for patients presenting in the first year with a large, constant angle, however, no published study provides a rationale for this restrictive definition. In this study, the present classification system for XT was evaluated and differences between infants with constant versus intermittent XT at presentation were characterized. Methods: Medical records of all patients diagnosed with XT before 12 months of age between 1980 and 1994 were identified by computer search. Exclusion criteria included previous eye muscle surgery, resolution of the XT by 3 months of age, and concomitant systemic or ocular disease. Patients were separated into intermittent XT and constant XT groups. The clinical characteristics and outcomes of these two groups were compared. Results: Of 2018 patients examined on our service during the first year of life for all causes, 23 (1.1 %) met the inclusion criteria. Follow-up data of more than 1 year was available for 13 patients, and of these, 46% had constant XT. The 2 groups had similar clinical features at presentation except for a larger initial angle in the constant XT group (P = .02). Average follow-up was 58 months (range: 13-158 months). Twelve patients (92%) required surgery. The reoperation rate was 27%, and 82% had final horizontal deviations of less than 10 PD. The incidence of A/V-patterns (38%), dissociated vertical deviation (46%), and binocularity (70%) was similar between groups. Conclusion: Half of infantile XT patients may present with intermittent XT, with similar clinical outcomes regardless of presentation. Surgical intervention resulted in successful alignment in most cases. More than half the patients developed measurable stereopsis, but none achieved bifixation. (J AAPOS 2001;5:352-6)
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ongenital exotropia (XT) has been defined as an idiopathic, large-angle, constant XT presenting in the first 6-12 months of life.1-6 This definition was most likely derived as a corollary to the more common and better-studied entity, congenital esotropia (ET).7 Previous studies of XT in infancy excluded patients who did not meet the above definition, which may have biased the characterization of these patients.1-4 As a result, little has been published concerning intermittent and small-angle XT in the first year of life. The purpose of this study was From the Krieger Children’s Eye Center at the Wilmer Institute,a the Department of Biomedical Engineering,b Johns Hopkins University School of Medicine, Baltimore, Maryland, and the University Hospital of Cleveland, Cleveland, Ohio.c This study was conducted at John Hopkins University School of Medicine. Portions of this material were presented at the 26th Annual Meeting of the American Association for Pediatric Ophthalmology and Strabismus, San Diego, California, April 14, 2000. Supported by the Research to Prevent Blindness Lew R. Wasserman Merit Award, the Whitaker Foundation, the Richard Starr Ross Clinician Scientist Award, the Roy and Niuta Titus Foundation, the Helena Rubinstein Foundation, New York, New York (D.G.H.), the National Children’s Eye Care Foundation, Dallas, Texas (F.J.E.), and the Judith and Paul Romano Binocular Vision and Strabismus Fellowship Endowment Fund. Submitted June 6, 2000. Revision accepted September 11, 2001. Reprint requests: David G. Hunter, MD, PhD, Wilmer Institute, 233, The Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287-9028; e-mail, [email protected]. Copyright © 2001 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2001/$35.00 + 0 75/1/120175 doi:10.1067/mpa.2001.120175
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to evaluate all healthy patients presenting with XT in the first year of life to determine whether findings and outcome parameters differed depending on the angle and intermittency of the strabismus at presentation.
SUBJECTS AND METHODS Records of all patients diagnosed with XT and ET before 12 months of age in the Wilmer Ophthalmological Institute between 1980 and 1994 were identified by computer search. Patients with strabismus caused by previous eye muscle surgery were excluded, as were patients whose ocular misalignment resolved by 3 months of age. Patients with any other ocular or systemic disease (including prematurity, defined as a gestational age less than 37 weeks)8 were excluded and were the subject of a separate study.9 Patients who were followed for less than 1 year were also excluded from the study. Patients with ocular conditions most likely associated with the strabismus (amblyopia, latent nystagmus, oblique muscle overaction, or dissociated vertical deviation) were not excluded. The following information was recorded when available: age, race, sex, intermittent versus constant strabismus, and size of initial ocular misalignment. The initial strabismus was measured at near by the Krimsky method. Prism diopters were converted to degrees before calculating mean or SD values to avoid errors of nonlinearity; the Journal of AAPOS
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TABLE 1. Initial evaluation (n = 13) Feature Age of onset (months) Spherical equivalent (diopters) Able to alternate fixation
Entire group
Intermittent XT (n = 7)
Constant XT (n = 6)
2.7 +0.75 (-1.00 – +4.10) 85%
3.8 +0.50 (-1.00 – +1.50) 86%
1.3 +1.00 (-0.90 – +4.10) 83%
P value .09 .60 1.00
XT, exotropia. P value refers to intermittent versus constant XT. Spherical equivalent includes all eyes.
results were then converted back to prism diopters. Spherical equivalent was calculated for all eyes in the group. To compare the clinical characteristics and outcome parameters, infants were placed in either the intermittent XT or constant XT group depending on the alignment at presentation. Age of onset was the age at which a parent or relative first observed an ocular misalignment. Patients were defined as having amblyopia if a fixation preference was treated using patching or penalization. The presence of alternate fixation was recorded. In some cases, patients with a fixation preference were capable of switching fixation to the opposite eye with examiner encouragement. Anisometropia of greater than 1.5 D or astigmatism of greater than 2 D was recorded. For outcome analysis, data from the most recent patient encounter were used. The magnitude and age of onset of an A- or V-pattern (A-patterns ≥ 10 PD, V-patterns ≥ 15 PD), dissociated vertical deviation, inferior or superior oblique overaction, and latent nystagmus were recorded. For binocular vision assessment, Worth 4-dot and Titmus stereo testing results were recorded. Minimal binocularity was defined as perception of the stereo fly or a fusion response on Worth 4-dot testing at near. Surgery was performed for a constant XT or for poor control or progressive loss of control of an intermittent XT. Surgical dosages were applied using standard tables.10 The date of surgery, type of surgery, and need for reoperation were recorded. Alignment at final follow-up examination was also noted. An undesirable outcome was defined as a final constant ocular misalignment of greater than or equal to 10 PD. Fisher’s Exact Test or Student’s t test was used for statistical analysis where appropriate. A 2-tailed P value of less than .05 was considered statistically significant.
RESULTS During the time-period covered, 2018 patients were examined in the Division of Pediatric Ophthalmology and Strabismus for any reason in the first year of life. Of these patients, 70 were diagnosed with XT and 310 were diagnosed with ET. Patients with coexisting ocular or systemic anomalies (as defined above) were the subjects of a separate study.9 The remaining group consisted of 23 patients with XT and 159 patients with ET. Thus, of infants examined in the first year of life for all causes, 1.1% had XT and
FIGURE. Angle of exotropia at presentation. A closed circle represents each patient. The horizontal line indicates the average strabismic deviation of each group. XT, exotropia.
7.9% had ET with no coexisting ocular or systemic abnormalities. The ET and XT patient populations were similar in race, sex, and age at initial examination. The parents first noted the ocular misalignment at a significantly later age in the XT patients (2.7 months) compared with the ET patients (0.8 months; P =.001). For the remainder of the study, patients followed for less than 1 year were excluded. The remaining database consisted of 13 patients presenting with XT in the first year of life. An intermittent deviation was documented in 7 (54%) patients at presentation (intermittent group). A constant deviation was documented in the remaining 6 (46%) patients (constant group). The clinical features of the intermittent and constant groups were similar at presentation (Table 1), except that the initial angle of XT at presentation was larger in the constant group (Figure, P = .02). There was a trend toward an earlier age of onset reported by parents in the constant group (P = .09). Average follow-up was 58 months (range: 13-158 months). Twelve of the 13 patients (92%) required surgery. One patient who presented with an intermittent XT of 40 at age 10 months was followed without surgery due to relatively good control of the alignment. At final follow up at age 7.5 years, she had no shift at distance but had an intermittent ET of 16 PD at near with no measurable stereop-
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TABLE 2. Surgical outcomes Outcome Surgery Age at surgery (months) Oblique surgery (initial operation) Reoperations XT < 10PD postop
Entire group
Intermittent XT
Constant XT
P value
12 (92%) 17 (6-43) 2 (17%) 3 (27%) 9 (82%)
6/7 18 1/5* 2/5* 4/5*
6/6 16 1/6 1/6 5/6
1.00 .79 1.00 .54 1.00
* One patient had surgery elsewhere, details not available. XT, exotropia. P-value refers to intermittent versus constant XT.
TABLE 3. Development of strabismus-associated abnormalities and binocularity
Strabismus-associated abnormalities Oblique muscle overaction Dissociated vertical deviation A or V pattern Latent nystagmus Amblyopia Rx Binocularity Bifixation* Stereo 200 arc sec Minimal binocularity
Entire group
Intermittent XT
Constant XT
4 (31%) 6 (46%) 5 (38%) 2 (15%) 4 (31%)
3 (1 IO, 2 SO) 3 2A 2 1
1 (1 IO) 3 2 A, 1 V 0 3
0 (0%) 2 (20%) 7 (70%)
0/6 2/6 4/6
0/4 0/4 3/4
XT, exotropia; Rx, treatment.
sis. In the surgical group, the reoperation rate was 27%. Surgical outcomes of the intermittent group versus the constant group were similar (Table 2). Associated clinical features were also similar between the two groups (Table 3). Gross binocularity developed in 7 of 10 testable patients (Table 3). No patient developed bifixation (stereopsis of 60 arc sec or better).
DISCUSSION Nomenclature Costenbader originally defined the terms congenital ET11 and infantile ET.12 He reserved congenital ET for infants with large-angle ET documented in the first 6 months of life, with no hypermetropia. He used infantile ET to describe the more heterogeneous population of patients with any ET presenting in the first year of life. Others have continued to modify and refine these definitions, and the terminology used to describe ET in infancy remains the subject of considerable debate.13-15 When XT presents during the first year of life, the terminology is even less-rigorously applied. Both congenital XT and infantile XT have been used to describe patients with large-angle deviations presenting in either the first 6 months of life or the first year of life, with a stable angle and normal central nervous system. In this study, the term infantile XT is used to describe otherwise-healthy patients presenting with XT in the first year of life. While the definition of congenital XT is analogous to that of congenital ET, there has been no systematic attempt to determine whether there is a reason for clinical studies to segregate infants with large-angle, constant
XT from those with smaller angle, intermittent XT at presentation. To address this concern, otherwise healthy patients with infantile XT, including those who did not meet the criteria for congenital XT, were studied. Because all patients studied were considered healthy, additional testing such as neuroimaging or developmental analysis was not routinely undertaken in this retrospective study. Any important coexisting disease would likely have been identified during the minimum followup period of 1 year. Prevalence XT was 8 times less common than ET the first year of life in our patient population (1.1% vs 7.9% prevalence, respectively). Archer et al16 estimated the prevalence of congenital ET in the general population as 0.1% to 0.5%. Biglan et al17 found that infantile XT was 30 times less common than infantile ET in their pediatric ophthalmology practice, with a prevalence of 0.1% for XT and 3.6% for ET among all patients seen in their practice. Our prevalence calculations, which included only patients examined in the first year of life in the denominator, also had a lower prevalence of XT but with a lower ratio. In contrast, Archer et al16 identified three congenital ET patients and two congenital XT patients in their study of more than 4000 infants in a neonatal nursery. Therefore, although some population studies indicate nearly equal prevalence of infantile XT and ET, the question of referral bias remains open to further investigation, and only rarely do patients present to the ophthalmologist with XT in the first year of life.
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Infantile XT: previous studies Hiles and Biglan18 reported 28 patients who required surgery for XT in the first 2 years of life. The age of onset was not reported, so it is not known how many of these patients could be considered to have infantile XT. Gross fusion (fusion response on Worth 4-dot testing at near) was achieved in 26 patients (93%). Stereopsis was documented in 21 patients (75%). In contrast, Moore and Cohen2 were unable to demonstrate gross fusion (method of fusion assessment not specified) in 7 patients with congenital XT. In our series, 7 of 10 testable patients (including 3 of 4 presenting with constant XT) achieved gross fusion. Two patients presenting with intermittent XT developed 200 arc seconds of stereopsis, although none of the constant XT patients achieved this level. Biglan et al17 reported on 12 patients with infantile XT (8 presenting with constant XT and 4 with intermittent XT) who were followed for an average of 7.9 years. Dissociated vertical deviation and inferior oblique muscle overaction were both present in 33% of patients at some point in the clinical course (developing after surgery in all but 1 case). No latent nystagmus was observed. Half of the patients had gross fusion as determined by Worth 4-dot testing, while 18% (2/11) had better than 200 arc seconds of stereopsis. The major difference between the study of Biglan et al and the present study was the larger number of reoperations reported by Biglan et al,17 which might be attributed to their longer follow-up period. Intermittent versus constant infantile XT It is unlikely that any of the patients in this study were normal patients inadvertently included because of a transient neonatal exodeviation. While a transient exodeviation is recognized to occur in newborns,19 ocular alignment usually is established within the first few months of life.19 Any patient with an ocular misalignment that resolved by age 3 months was excluded from this study. Although such transient neonatal XTs have been observed to persist for longer than 3 months, none of our patients who had an onset of XT before 4 months of age showed spontaneous resolution at a later date over a minimum 1year follow-up. Approximately equal numbers of XT patients presented with intermittent versus constant XT. Although the number of patients in this study is limited, the presentation, associations, and outcome of patients presenting with intermittent XT was similar to that of patients presenting with constant XT. Biglan et al17 also included patients presenting with intermittent and constant XT in their infantile XT group. They observed no better outcome in the patients presenting with intermittent XT. In particular, 1 of 4 of their intermittent XT patients developed dissociated vertical deviation, another developed inferior oblique muscle overaction, 3 of 4 required surgery, and only 1 of 3 testable patients achieved stereopsis of 200 arc seconds or better. Thus, other than the larger strabismus angle
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observed in constant XT patients at presentation in the present study, a clear clinical distinction between the characteristics and clinical outcomes of patients presenting with intermittent versus constant XT has not been observed in the 2 studies that have addressed this issue. This raises fundamental questions: Is constant infantile XT a different disease than intermittent infantile XT, or are they variable expressions of the same disease? Two observations in the present study support the latter hypothesis. First, the timing of the initial examination may determine which patients are designated as intermittent XT. For example, 1 patient with infantile XT presented with an intermittent exodeviation at 4 months of age. This patient’s strabismus became a constant, 70-PD XT by age 8 months, and he underwent bilateral lateral rectus recessions and developed superior oblique overaction, dissociated vertical deviation, latent nystagmus, and amblyopia. Had this patient first been examined at age 8 months, he would have been considered to have congenital XT by all published definitions. Second, manifestations such as A/V patterns, dissociated vertical deviation, or oblique dysfunction, which might be expected to be more common in patients presenting with a constant deviation, were uncommon in both the constant and intermittent infantile XT patients. The trend toward a slightly better binocular outcome in patients presenting with an intermittent deviation supports the concept that these 2 groups are distinct, but only a small number of patients were cooperative enough to measure binocular vision reliably, numbers too small for meaningful statistical analysis. Congenital XT At least 1 of our patients (and 2 of Biglan et al’s patients)17 initially presented with intermittent XT, but subsequently met the strictest criteria for congenital XT. An additional 6 of our patients (and 8 of Biglan et al’s patients)17 met strict criteria for congenital XT at initial presentation. Therefore, 21% of patients (3 of 14) who eventually met all of the criteria for congenital XT presented with intermittent XT. Previous studies of congenital XT may therefore have been biased by exclusion of patients presenting with intermittent XT. We recommend that future studies of this rare condition should not automatically exclude patients initially presenting with intermittent or small angle XT, as long as the ocular misalignment is present after 3 months of age. In conclusion, infantile XT is rare and therefore difficult to study clinically. Previous reports have assumed that patients must present with a constant, large angle deviation; however, when all patients presenting with XT in the first year of life are considered, it is evident that many patients will present with a smaller-angle or intermittent misalignment. Some of these intermittent infantile XT patients will later develop a constant deviation. Over 90% of patients with infantile XT, whether constant or intermittent, will eventually require surgery, resulting in suc-
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cessful alignment and at least minimal binocularity in most cases. Thus, when the clinical features and outcomes of all infantile XT patients are analyzed, it appears that they may represent a spectrum of the same entity. We recommend that future studies of this rare condition not automatically exclude patients initially presenting with intermittent XT, as long as the ocular misalignment is present after 3 months of age. References 1. Williams F, Beneish R, Polomeno RC, Little JM. Congenital exotropia. Am Orthoptic J 1984;34:92-4. 2. Moore S, Cohen RL. Congenital exotropia. Am Orthoptic J 1985; 35:68-70. 3. Rubin SE, Nelson LB, Wagner RS, et al. Infantile exotropia in healthy children. Ophthalmic Surg 1988;19:792-3. 4. Biedner B, Marcus M, David R, Yassur Y. Congenital constant exotropia: surgical results in six patients. Binocular Vis Eye Muscle Surg Q 1993;8:137-40. 5. Harley RD. Pediatric ophthalmology, 2nd ed. Philadelphia: WB Saunders; 1983. p. 237. 6. Parks MM, Mitchell PR. Concomitant exodeviations. In: Tasman W, Jaeger EA, editors. Duane’s clinical ophthalmology, revised ed. Philadelphia: JB Lippincott, 1999; vol 1, chap 13. pp. 1-12. 7. Von Noorden GK. Binocular vision and ocular motility. 5th ed. St. Louis: CV Mosby; 1996. p. 344.
8. Behrman RE, Shiono PH. Neonatal risk factors. In: Fanaroff AA, Martin RJ, editors. Neonatal-perinatal medicine: diseases of the fetus and infant, 5th ed. St Louis: CV Mosby; 1992. p. 4. 9. Hunter DG, Ellis FJ. Prevalence of systemic and ocular disease in infantile exotropia: comparison with infantile esotropia. Ophthalmology 1999;106:1951-6. 10. Guyton DL. Strabismus surgery. In: Rice TA, Michels RG, Stark WJ, editors. Ophthalmic surgery, 4th ed. St. Louis: Mosby; 1984. p. 89. 11. Costenbader FD. In: Allen JH, editor. Strabismus ophthalmic symposium. St. Louis: Mosby; 1958. p. 339. 12. Costenbader FD. Infantile esotopia. Trans Am Ophthalmol Soc 1961;59:397-429. 13. Von Noorden, GK. A reassessment of infantile esotropia. Am J Ophthalmol 1988;105:1-10. 14. Helveston EM. Esotropia in the first year of life. Trans New Orleans Acad Ophthalmol 1986;34:419-29. 15. Parks MM. Congenital esotropia versus infantile esotropia. Graefes Arch Clin Exp Ophthalmol 1988;226:106-7. 16. Archer SM, Sondhi N, Helveston EM. Strabismus in infancy. Ophthalmology 1989;96:133-7. 17. Biglan AW, Davis JS, Cheng KP, Pettapiece MC. Infantile exotropia. J Pediatr Ophthalmol Strabismus 1996;33:79-84. 18. Hiles DA, Biglan AW. Early surgery of infantile exotropia. Trans Pa Acad of Ophthalmol Otolaryngol 1983;136:161-8. 19. Nixon RB, Helveston EM, Miller K, et al. Incidence of strabismus in neonates. Am J Ophthalmol 1985;100:798-801.
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ongenital exotropia (XT) has been defined as an idiopathic, large-angle, constant XT presenting in the first 6-12 months of life.1-6 This definition was most likely derived as a corollary to the more common and better-studied entity, congenital esotropia (ET).7 Previous studies of XT in infancy excluded patients who did not meet the above definition, which may have biased the characterization of these patients.1-4 As a result, little has been published concerning intermittent and small-angle XT in the first year of life. The purpose of this study was From the Krieger Children’s Eye Center at the Wilmer Institute,a the Department of Biomedical Engineering,b Johns Hopkins University School of Medicine, Baltimore, Maryland, and the University Hospital of Cleveland, Cleveland, Ohio.c This study was conducted at John Hopkins University School of Medicine. Portions of this material were presented at the 26th Annual Meeting of the American Association for Pediatric Ophthalmology and Strabismus, San Diego, California, April 14, 2000. Supported by the Research to Prevent Blindness Lew R. Wasserman Merit Award, the Whitaker Foundation, the Richard Starr Ross Clinician Scientist Award, the Roy and Niuta Titus Foundation, the Helena Rubinstein Foundation, New York, New York (D.G.H.), the National Children’s Eye Care Foundation, Dallas, Texas (F.J.E.), and the Judith and Paul Romano Binocular Vision and Strabismus Fellowship Endowment Fund. Submitted June 6, 2000. Revision accepted September 11, 2001. Reprint requests: David G. Hunter, MD, PhD, Wilmer Institute, 233, The Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287-9028; e-mail, [email protected]. Copyright © 2001 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2001/$35.00 + 0 75/1/120175 doi:10.1067/mpa.2001.120175
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to evaluate all healthy patients presenting with XT in the first year of life to determine whether findings and outcome parameters differed depending on the angle and intermittency of the strabismus at presentation.
SUBJECTS AND METHODS Records of all patients diagnosed with XT and ET before 12 months of age in the Wilmer Ophthalmological Institute between 1980 and 1994 were identified by computer search. Patients with strabismus caused by previous eye muscle surgery were excluded, as were patients whose ocular misalignment resolved by 3 months of age. Patients with any other ocular or systemic disease (including prematurity, defined as a gestational age less than 37 weeks)8 were excluded and were the subject of a separate study.9 Patients who were followed for less than 1 year were also excluded from the study. Patients with ocular conditions most likely associated with the strabismus (amblyopia, latent nystagmus, oblique muscle overaction, or dissociated vertical deviation) were not excluded. The following information was recorded when available: age, race, sex, intermittent versus constant strabismus, and size of initial ocular misalignment. The initial strabismus was measured at near by the Krimsky method. Prism diopters were converted to degrees before calculating mean or SD values to avoid errors of nonlinearity; the Journal of AAPOS
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TABLE 1. Initial evaluation (n = 13) Feature Age of onset (months) Spherical equivalent (diopters) Able to alternate fixation
Entire group
Intermittent XT (n = 7)
Constant XT (n = 6)
2.7 +0.75 (-1.00 – +4.10) 85%
3.8 +0.50 (-1.00 – +1.50) 86%
1.3 +1.00 (-0.90 – +4.10) 83%
P value .09 .60 1.00
XT, exotropia. P value refers to intermittent versus constant XT. Spherical equivalent includes all eyes.
results were then converted back to prism diopters. Spherical equivalent was calculated for all eyes in the group. To compare the clinical characteristics and outcome parameters, infants were placed in either the intermittent XT or constant XT group depending on the alignment at presentation. Age of onset was the age at which a parent or relative first observed an ocular misalignment. Patients were defined as having amblyopia if a fixation preference was treated using patching or penalization. The presence of alternate fixation was recorded. In some cases, patients with a fixation preference were capable of switching fixation to the opposite eye with examiner encouragement. Anisometropia of greater than 1.5 D or astigmatism of greater than 2 D was recorded. For outcome analysis, data from the most recent patient encounter were used. The magnitude and age of onset of an A- or V-pattern (A-patterns ≥ 10 PD, V-patterns ≥ 15 PD), dissociated vertical deviation, inferior or superior oblique overaction, and latent nystagmus were recorded. For binocular vision assessment, Worth 4-dot and Titmus stereo testing results were recorded. Minimal binocularity was defined as perception of the stereo fly or a fusion response on Worth 4-dot testing at near. Surgery was performed for a constant XT or for poor control or progressive loss of control of an intermittent XT. Surgical dosages were applied using standard tables.10 The date of surgery, type of surgery, and need for reoperation were recorded. Alignment at final follow-up examination was also noted. An undesirable outcome was defined as a final constant ocular misalignment of greater than or equal to 10 PD. Fisher’s Exact Test or Student’s t test was used for statistical analysis where appropriate. A 2-tailed P value of less than .05 was considered statistically significant.
RESULTS During the time-period covered, 2018 patients were examined in the Division of Pediatric Ophthalmology and Strabismus for any reason in the first year of life. Of these patients, 70 were diagnosed with XT and 310 were diagnosed with ET. Patients with coexisting ocular or systemic anomalies (as defined above) were the subjects of a separate study.9 The remaining group consisted of 23 patients with XT and 159 patients with ET. Thus, of infants examined in the first year of life for all causes, 1.1% had XT and
FIGURE. Angle of exotropia at presentation. A closed circle represents each patient. The horizontal line indicates the average strabismic deviation of each group. XT, exotropia.
7.9% had ET with no coexisting ocular or systemic abnormalities. The ET and XT patient populations were similar in race, sex, and age at initial examination. The parents first noted the ocular misalignment at a significantly later age in the XT patients (2.7 months) compared with the ET patients (0.8 months; P =.001). For the remainder of the study, patients followed for less than 1 year were excluded. The remaining database consisted of 13 patients presenting with XT in the first year of life. An intermittent deviation was documented in 7 (54%) patients at presentation (intermittent group). A constant deviation was documented in the remaining 6 (46%) patients (constant group). The clinical features of the intermittent and constant groups were similar at presentation (Table 1), except that the initial angle of XT at presentation was larger in the constant group (Figure, P = .02). There was a trend toward an earlier age of onset reported by parents in the constant group (P = .09). Average follow-up was 58 months (range: 13-158 months). Twelve of the 13 patients (92%) required surgery. One patient who presented with an intermittent XT of 40 at age 10 months was followed without surgery due to relatively good control of the alignment. At final follow up at age 7.5 years, she had no shift at distance but had an intermittent ET of 16 PD at near with no measurable stereop-
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TABLE 2. Surgical outcomes Outcome Surgery Age at surgery (months) Oblique surgery (initial operation) Reoperations XT < 10PD postop
Entire group
Intermittent XT
Constant XT
P value
12 (92%) 17 (6-43) 2 (17%) 3 (27%) 9 (82%)
6/7 18 1/5* 2/5* 4/5*
6/6 16 1/6 1/6 5/6
1.00 .79 1.00 .54 1.00
* One patient had surgery elsewhere, details not available. XT, exotropia. P-value refers to intermittent versus constant XT.
TABLE 3. Development of strabismus-associated abnormalities and binocularity
Strabismus-associated abnormalities Oblique muscle overaction Dissociated vertical deviation A or V pattern Latent nystagmus Amblyopia Rx Binocularity Bifixation* Stereo 200 arc sec Minimal binocularity
Entire group
Intermittent XT
Constant XT
4 (31%) 6 (46%) 5 (38%) 2 (15%) 4 (31%)
3 (1 IO, 2 SO) 3 2A 2 1
1 (1 IO) 3 2 A, 1 V 0 3
0 (0%) 2 (20%) 7 (70%)
0/6 2/6 4/6
0/4 0/4 3/4
XT, exotropia; Rx, treatment.
sis. In the surgical group, the reoperation rate was 27%. Surgical outcomes of the intermittent group versus the constant group were similar (Table 2). Associated clinical features were also similar between the two groups (Table 3). Gross binocularity developed in 7 of 10 testable patients (Table 3). No patient developed bifixation (stereopsis of 60 arc sec or better).
DISCUSSION Nomenclature Costenbader originally defined the terms congenital ET11 and infantile ET.12 He reserved congenital ET for infants with large-angle ET documented in the first 6 months of life, with no hypermetropia. He used infantile ET to describe the more heterogeneous population of patients with any ET presenting in the first year of life. Others have continued to modify and refine these definitions, and the terminology used to describe ET in infancy remains the subject of considerable debate.13-15 When XT presents during the first year of life, the terminology is even less-rigorously applied. Both congenital XT and infantile XT have been used to describe patients with large-angle deviations presenting in either the first 6 months of life or the first year of life, with a stable angle and normal central nervous system. In this study, the term infantile XT is used to describe otherwise-healthy patients presenting with XT in the first year of life. While the definition of congenital XT is analogous to that of congenital ET, there has been no systematic attempt to determine whether there is a reason for clinical studies to segregate infants with large-angle, constant
XT from those with smaller angle, intermittent XT at presentation. To address this concern, otherwise healthy patients with infantile XT, including those who did not meet the criteria for congenital XT, were studied. Because all patients studied were considered healthy, additional testing such as neuroimaging or developmental analysis was not routinely undertaken in this retrospective study. Any important coexisting disease would likely have been identified during the minimum followup period of 1 year. Prevalence XT was 8 times less common than ET the first year of life in our patient population (1.1% vs 7.9% prevalence, respectively). Archer et al16 estimated the prevalence of congenital ET in the general population as 0.1% to 0.5%. Biglan et al17 found that infantile XT was 30 times less common than infantile ET in their pediatric ophthalmology practice, with a prevalence of 0.1% for XT and 3.6% for ET among all patients seen in their practice. Our prevalence calculations, which included only patients examined in the first year of life in the denominator, also had a lower prevalence of XT but with a lower ratio. In contrast, Archer et al16 identified three congenital ET patients and two congenital XT patients in their study of more than 4000 infants in a neonatal nursery. Therefore, although some population studies indicate nearly equal prevalence of infantile XT and ET, the question of referral bias remains open to further investigation, and only rarely do patients present to the ophthalmologist with XT in the first year of life.
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Infantile XT: previous studies Hiles and Biglan18 reported 28 patients who required surgery for XT in the first 2 years of life. The age of onset was not reported, so it is not known how many of these patients could be considered to have infantile XT. Gross fusion (fusion response on Worth 4-dot testing at near) was achieved in 26 patients (93%). Stereopsis was documented in 21 patients (75%). In contrast, Moore and Cohen2 were unable to demonstrate gross fusion (method of fusion assessment not specified) in 7 patients with congenital XT. In our series, 7 of 10 testable patients (including 3 of 4 presenting with constant XT) achieved gross fusion. Two patients presenting with intermittent XT developed 200 arc seconds of stereopsis, although none of the constant XT patients achieved this level. Biglan et al17 reported on 12 patients with infantile XT (8 presenting with constant XT and 4 with intermittent XT) who were followed for an average of 7.9 years. Dissociated vertical deviation and inferior oblique muscle overaction were both present in 33% of patients at some point in the clinical course (developing after surgery in all but 1 case). No latent nystagmus was observed. Half of the patients had gross fusion as determined by Worth 4-dot testing, while 18% (2/11) had better than 200 arc seconds of stereopsis. The major difference between the study of Biglan et al and the present study was the larger number of reoperations reported by Biglan et al,17 which might be attributed to their longer follow-up period. Intermittent versus constant infantile XT It is unlikely that any of the patients in this study were normal patients inadvertently included because of a transient neonatal exodeviation. While a transient exodeviation is recognized to occur in newborns,19 ocular alignment usually is established within the first few months of life.19 Any patient with an ocular misalignment that resolved by age 3 months was excluded from this study. Although such transient neonatal XTs have been observed to persist for longer than 3 months, none of our patients who had an onset of XT before 4 months of age showed spontaneous resolution at a later date over a minimum 1year follow-up. Approximately equal numbers of XT patients presented with intermittent versus constant XT. Although the number of patients in this study is limited, the presentation, associations, and outcome of patients presenting with intermittent XT was similar to that of patients presenting with constant XT. Biglan et al17 also included patients presenting with intermittent and constant XT in their infantile XT group. They observed no better outcome in the patients presenting with intermittent XT. In particular, 1 of 4 of their intermittent XT patients developed dissociated vertical deviation, another developed inferior oblique muscle overaction, 3 of 4 required surgery, and only 1 of 3 testable patients achieved stereopsis of 200 arc seconds or better. Thus, other than the larger strabismus angle
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observed in constant XT patients at presentation in the present study, a clear clinical distinction between the characteristics and clinical outcomes of patients presenting with intermittent versus constant XT has not been observed in the 2 studies that have addressed this issue. This raises fundamental questions: Is constant infantile XT a different disease than intermittent infantile XT, or are they variable expressions of the same disease? Two observations in the present study support the latter hypothesis. First, the timing of the initial examination may determine which patients are designated as intermittent XT. For example, 1 patient with infantile XT presented with an intermittent exodeviation at 4 months of age. This patient’s strabismus became a constant, 70-PD XT by age 8 months, and he underwent bilateral lateral rectus recessions and developed superior oblique overaction, dissociated vertical deviation, latent nystagmus, and amblyopia. Had this patient first been examined at age 8 months, he would have been considered to have congenital XT by all published definitions. Second, manifestations such as A/V patterns, dissociated vertical deviation, or oblique dysfunction, which might be expected to be more common in patients presenting with a constant deviation, were uncommon in both the constant and intermittent infantile XT patients. The trend toward a slightly better binocular outcome in patients presenting with an intermittent deviation supports the concept that these 2 groups are distinct, but only a small number of patients were cooperative enough to measure binocular vision reliably, numbers too small for meaningful statistical analysis. Congenital XT At least 1 of our patients (and 2 of Biglan et al’s patients)17 initially presented with intermittent XT, but subsequently met the strictest criteria for congenital XT. An additional 6 of our patients (and 8 of Biglan et al’s patients)17 met strict criteria for congenital XT at initial presentation. Therefore, 21% of patients (3 of 14) who eventually met all of the criteria for congenital XT presented with intermittent XT. Previous studies of congenital XT may therefore have been biased by exclusion of patients presenting with intermittent XT. We recommend that future studies of this rare condition should not automatically exclude patients initially presenting with intermittent or small angle XT, as long as the ocular misalignment is present after 3 months of age. In conclusion, infantile XT is rare and therefore difficult to study clinically. Previous reports have assumed that patients must present with a constant, large angle deviation; however, when all patients presenting with XT in the first year of life are considered, it is evident that many patients will present with a smaller-angle or intermittent misalignment. Some of these intermittent infantile XT patients will later develop a constant deviation. Over 90% of patients with infantile XT, whether constant or intermittent, will eventually require surgery, resulting in suc-
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cessful alignment and at least minimal binocularity in most cases. Thus, when the clinical features and outcomes of all infantile XT patients are analyzed, it appears that they may represent a spectrum of the same entity. We recommend that future studies of this rare condition not automatically exclude patients initially presenting with intermittent XT, as long as the ocular misalignment is present after 3 months of age. References 1. Williams F, Beneish R, Polomeno RC, Little JM. Congenital exotropia. Am Orthoptic J 1984;34:92-4. 2. Moore S, Cohen RL. Congenital exotropia. Am Orthoptic J 1985; 35:68-70. 3. Rubin SE, Nelson LB, Wagner RS, et al. Infantile exotropia in healthy children. Ophthalmic Surg 1988;19:792-3. 4. Biedner B, Marcus M, David R, Yassur Y. Congenital constant exotropia: surgical results in six patients. Binocular Vis Eye Muscle Surg Q 1993;8:137-40. 5. Harley RD. Pediatric ophthalmology, 2nd ed. Philadelphia: WB Saunders; 1983. p. 237. 6. Parks MM, Mitchell PR. Concomitant exodeviations. In: Tasman W, Jaeger EA, editors. Duane’s clinical ophthalmology, revised ed. Philadelphia: JB Lippincott, 1999; vol 1, chap 13. pp. 1-12. 7. Von Noorden GK. Binocular vision and ocular motility. 5th ed. St. Louis: CV Mosby; 1996. p. 344.
8. Behrman RE, Shiono PH. Neonatal risk factors. In: Fanaroff AA, Martin RJ, editors. Neonatal-perinatal medicine: diseases of the fetus and infant, 5th ed. St Louis: CV Mosby; 1992. p. 4. 9. Hunter DG, Ellis FJ. Prevalence of systemic and ocular disease in infantile exotropia: comparison with infantile esotropia. Ophthalmology 1999;106:1951-6. 10. Guyton DL. Strabismus surgery. In: Rice TA, Michels RG, Stark WJ, editors. Ophthalmic surgery, 4th ed. St. Louis: Mosby; 1984. p. 89. 11. Costenbader FD. In: Allen JH, editor. Strabismus ophthalmic symposium. St. Louis: Mosby; 1958. p. 339. 12. Costenbader FD. Infantile esotopia. Trans Am Ophthalmol Soc 1961;59:397-429. 13. Von Noorden, GK. A reassessment of infantile esotropia. Am J Ophthalmol 1988;105:1-10. 14. Helveston EM. Esotropia in the first year of life. Trans New Orleans Acad Ophthalmol 1986;34:419-29. 15. Parks MM. Congenital esotropia versus infantile esotropia. Graefes Arch Clin Exp Ophthalmol 1988;226:106-7. 16. Archer SM, Sondhi N, Helveston EM. Strabismus in infancy. Ophthalmology 1989;96:133-7. 17. Biglan AW, Davis JS, Cheng KP, Pettapiece MC. Infantile exotropia. J Pediatr Ophthalmol Strabismus 1996;33:79-84. 18. Hiles DA, Biglan AW. Early surgery of infantile exotropia. Trans Pa Acad of Ophthalmol Otolaryngol 1983;136:161-8. 19. Nixon RB, Helveston EM, Miller K, et al. Incidence of strabismus in neonates. Am J Ophthalmol 1985;100:798-801.