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Incidence and types of childhood exotropia
Incidence and Types of Childhood Exotropia A Population-Based Study Malu Govindan, BA,1 Brian G. Mohney, MD,2 Nancy N. Diehl, BS,3 James P. Burke, PhD4 Objective: To determine the incidence and types of childhood exotropia in a defined population. Design: Retrospective, population-based cohort. Participants: All pediatric (⬍19 years old) residents of Olmsted County, Minnesota diagnosed with an exodeviation (ⱖ10 prism diopters) from January 1, 1985 through December 31, 1994. Methods: The medical records of all potential patients identified by the resources of the Rochester Epidemiology Project were reviewed. Main Outcome Measures: Incidence and types of childhood exotropia. Results: Two hundred five cases of childhood exotropia were identified during the 10-year period, yielding an annual age- and gender-adjusted incidence of 64.1 (95% confidence interval: 55.2–72.9)/100 000 patients younger than 19 years. This rate corresponds to a prevalence of approximately 1.0% of all children younger than 11 years, with a significant decrease in the incidence during the second decade of life (P⬍0.001). Eighty-six percent of the children had intermittent exotropia, convergence insufficiency, or an exotropia in the setting of an abnormal central nervous system. Conclusions: The incidence of childhood exotropia from this population-based study is comparable to the prevalence rates in prior reports. Exotropia is most prevalent during the first decade of life, with intermittent exotropia and convergence insufficiency occurring most frequently. Ophthalmology 2005;112:104 –108 © 2005 by the American Academy of Ophthalmology.
Exotropia is a disorder of ocular alignment characterized by an outward deviation of the eyes. Although recently reported to occur more frequently than esotropia in Asians,1 exodeviations are much less common than esodeviations among Western populations.2,3 However, existing epidemiologic reports of childhood exotropia predominantly rely on mass screenings of variable populations, often by nonophthalmic specialists, and provide little information on the true population-based incidence of this disorder.2– 8 Populationbased data on the incidence and specific forms of exotropia, each with its own epidemiologic profile, would be useful in the allocation of health care resources and the development of clinical trials. The primary objective of this study was to determine the incidence and types of exotropia among pa-
Originally received: March 29, 2004. Accepted: July 23, 2004. Manuscript no. 240233. 1 Mayo Clinic College of Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. 2 Department of Ophthalmology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. 3 Division of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. 4 Division of Epidemiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. Correspondence to Brian G. Mohney, MD, Mayo Clinic, Department of Ophthalmology, 200 First Street Southwest, Rochester, MN 55905. E-mail: [email protected].
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© 2005 by the American Academy of Ophthalmology Published by Elsevier Inc.
tients younger than 19 years diagnosed during a 10-year period using a population-based medical record retrieval system.
Subjects and Methods The medical records of all patients younger than 19 years who were residing in Olmsted County, Minnesota and diagnosed with exotropia from January 1, 1985 through December 31, 1994 were retrospectively reviewed. Potential cases of exotropia were identified by using the resources of the Rochester Epidemiology Project, a medical records linkage system designed to capture data on any patient–physician encounter in Olmsted County, Minnesota.9,10 The population of this upper Midwest community of the United States (106 470 in 1990) is relatively isolated from other urban areas, and virtually all medical care is provided to county residents by Mayo Clinic or Olmsted Medical Group and their affiliated hospitals. Institutional review board approval was obtained for this study. We reviewed the medical records of all patients 0 through 18 years of age who were diagnosed by an ophthalmologist as having exotropia, hypertropia, or an unspecified strabismus from 1984 through 1999. We also reviewed the records of pediatric patients who were, during the same interval, diagnosed with cranial nerve palsies, retinal disorders, cataract, corneal scarring, optic nerve disorders, and developmental delay to avoid missing any potential cases of secondary exotropia. All diagnoses are entered into the Rochester Epidemiology Project database by trained personnel who review the entire medical record. There were 2 to 3 active optometric practices within Olmsted County during the time of this study. However, these practices uncommonly evaluated pediatric patients; a recent computer search of exotropic patients examined ISSN 0161-6420/05/$–see front matter doi:10.1016/j.ophtha.2004.07.033
Govindan et al 䡠 Incidence and Types of Childhood Exotropia Table 1. Incidence of Childhood Exotropia in Olmsted County, Minnesota, 1985 to 1994
Age Group (yrs) 0–1 2–3 4–5 6–7 8–9 10–11 12–13 14–15 16–17 18 Total Age/gender adjusted total
Female Incidence Rates (per 100 000 Patients Younger than 19)
Male Incidence Rates (per 100 000 Patients Younger than 19)
Total Incidence Rates (per 100 000 Patients Younger than 19)
58.0 142.0 81.4 102.0 142.3 49.8 54.9 28.1 6.8 30.5 74.2
61.3 79.4 49.2 79.2 84.8 52.3 33.2 51.9 34.8 44.0 58.8
59.7 110.7 64.8 90.3 112.3 51.1 43.9 40.5 20.7 37.4 66.3 64.1
during a 4-year period (January 1, 2000 –December 31, 2003) by one 3-person practice yielded 5 exotropic patients, only 1 of whom was younger than 19. Trained residency checkers verified patients’ residency status at the time of birth and at diagnosis using information from city and county directories. Patients not residing in Olmsted County at the time of their diagnosis were excluded. Sixty-six (3.94%) of the 1672 potential patients refused research authorization, and their medical records were not reviewed. The ophthalmic records of the remaining 1606 potential cases were reviewed. Except for those with convergence insufficiency or a paralytic deviation, all patients diagnosed with an intermittent or constant exotropia of ⱖ10 prism diopters (PD; at either distance or near in the primary position) during the study period were included. The angle of deviation was measured by the prism and alternative cover technique at both distance and near for most patients, although the Krimsky prism technique was necessary in infants, some young children, and those with neurologic deficits. Patients with convergence insufficiency were enrolled if they were symptomatic and displayed a near deviation of ⱖ4 PD, or asymptomatic with a deviation of ⱖ10 PD, with most being orthotropic in the distance. Two of the 8 children with paralytic strabismus (e.g., Duane’s type II or type III retraction syndrome or third cranial nerve palsy) displayed ⬍10 PD of exotropia in the primary position but, because their strabismus predominantly resulted in an exotropic deviation, were included in the study. The entire medical record of those diagnosed with exotropia was carefully reviewed for any developmental, neurologic, or ocular disorder that might have caused or been associated with the exotropic deviation. The following criteria were used to classify the various types of childhood exotropia.11 Intermittent exotropia was defined as an acquired deviation that was either intermittent or, if constant, not associated with dissociated strabismus and demonstrated 50 arc seconds or better of stereopsis either before or after strabismus surgery. Congenital exotropia included neurologically intact children with a constant deviation that developed by 6 months of age. Exotropic children with a congenital or acquired developmental or neurologic disorder were grouped under central nervous system (CNS) defects regardless of the age at onset. Because it was impossible to correlate CNS disease severity with the development of strabismus, any form of neurologic impairment except isolated speech delay was included in this category. Sensory exotropia included patients with a unilateral or bilateral ocular condition that prevented normal fusion. Postoperative consecutive exotropia was not included in this series because it is not a naturally occurring form of strabismus. No patient was placed in more than one diagnostic group. Annual age- and gender-specific incidence rates were con-
structed using the age- and gender-specific population figures for Olmsted County, Minnesota from the United States census. Ageand gender-specific denominators for individual years were generated from linear interpolation of the 1970, 1980, 1990, and 2000 census figures. The 95% confidence intervals (CIs) were calculated with assumptions based on the Poisson distribution. Trends over time, by age, and between genders were investigated using Poisson regression models.
Results Two hundred five new cases of childhood exotropia were identified in Olmsted County, Minnesota during the 10-year study period. There were 112 female (54.6%) and 93 male (45.4%) incident cases. The age- and gender- adjusted annual incidence rate for exotropia was 64.1/100 000 patients younger than 19 years (Table 1), with a significant decrease in the second decade of life (P⬍0.001). There was a bimodal peak in diagnosis at approximately 3 years of age and again at 9 years. The overall ageadjusted incidence among girls (71.0/100 000) was slightly greater than that among boys (57.5/100 000). Girls tended to be more likely than boys to develop exotropia during the first decade, whereas boys were more commonly exotropic during the teenage years (P ⫽ 0.10), as shown in Figure 1. Numbers of children diagnosed with exotropia were similar throughout the 10-year period. Table 2 shows the cumulative incidence rates by age calculated from our incidence data. Although the cumulative incidence steadily increases through age 18, the vast majority of patients were diagnosed by age 10, corresponding to a prevalence of approximately 1.0%. The additive nature of Table 2 assumes no spontaneous resolution of the exotropias diagnosed in this study. Table 3 shows the relative frequencies and incidence rates for the various types of childhood exotropia. Intermittent exotropia was the most frequently diagnosed form of exotropia, comprising 51.7% of all study patients, with an incidence rate of 32.1/100 000 patients younger than 19 years. Convergence insufficiency was found in 40 children (19.5%), corresponding to an incidence of 13.7/100 000. The specific CNS defects associated with 30 of the exotropic children are shown in Table 4, whereas the causes of sensory exotropia in the 17 children with this condition are shown in Table 5. Paralytic (8), congenital (1), and the undetermined (3) forms of exotropia had a combined incidence rate of 3.9/100 000 patients younger than 19.
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Ophthalmology Volume 112, Number 1, January 2005 Table 3. Observed Types of Exotropia among 205 Consecutive Patients Younger than 19 Years in Olmsted County, Minnesota, 1985 to 1994
Figure 1. Incidence rates of childhood exotropia by age in Olmsted County, Minnesota, 1985 to 1994 (3-year running average).
Discussion This study provides data on the incidence of childhood exotropia in a geographically defined population. We found an annual age- and gender-adjusted incidence of 64.1 (95% CI: 55.2–72.9)/100 000 patients younger than 19 years. The incidence rate was highest in the first decade of life, with a prevalence or cumulative incidence of 1.0%. New cases of exotropia significantly decreased in the second decade of life. Although girls were more likely than boys to be diagnosed with exotropia, there was no significant difference between the genders, nor was there a significant change in the incidence rate over the 10-year study period. Published studies on the prevalence of strabismus have included preverbal children,5,7 children 6 to 7 years old,3,4,6,8 and a more comprehensive review of children between birth and 19 years.2 However, these studies were Table 2. Cumulative Incidence of Childhood Exotropia in Olmsted County, Minnesota, 1985 to 1994 Age Group (yrs) 0–2 0–3 0–4 0–5 0–6 0–7 0–8 0–9 0–10 0–11 0–12 0–13 0–14 0–15 0–16 0–17 0–18
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Cumulative Incidence (%)
Cumulative n
0.25 0.37 0.40 0.51 0.61 0.69 0.79 0.92 0.98 1.03 1.08 1.11 1.15 1.18 1.21 1.22 1.25
41 60 66 83 101 114 130 152 161 169 178 182 189 194 198 200 205
Exotropia Type
n
%
Intermittent* Convergence insufficiency Abnormal central nervous system Sensory Paralytic Congenital Other (undetermined)
106 40 30 17 8 1 3
51.7 19.5 14.6 8.25 3.9 0.5 1.5
Incidence per 100 000 Patients Younger than 19 (CI) 32.1 (25.9–38.2) 13.7 (9.5–18.0) 9.1 (5.9–12.4) 5.3 (2.7–7.8) † † †
CI ⫽ age- and gender-adjusted 95% confidence interval. *One had a constant deviation at presentation. † The combined incidence rate of the paralytic, congenital, and undetermined forms of exotropia was 3.9 (1.7– 6.1, CI) per 100 000 patients younger than 19.
comprised of mass screenings of selected children and were not population-based efforts. Moreover, most were performed exclusively by orthoptists or specially trained nurses and were not commonly performed or confirmed by an ophthalmologist. Despite these limitations, the prevalence rates from these reports may be compared with the cumulative incidence values calculated from this study (Table 2) by adjusting for the age at which the prior studies were conducted. Two reports have described the prevalence of strabismus among preverbal children.5,7 Kornder et al reported an exotropia prevalence of 1.0% among 1074 children from 6 to 30 months of age.5 Friedman et al, reporting on 38 000 similarly aged children, found exotropia to occur in only 0.30%.7 Kornder et al’s prevalence estimate of ⬎3 times that of Friedman et al is likely due to the former’s screening of children from high-risk families (positive family history) as identified by a prescreening questionnaire. The cumulaTable 4. Disorders Contributing to Documented Central Nervous System (CNS) Impairment among 30 Children with Exotropia CNS Disorder
n
Cerebral palsy Developmental delay Crouzon’s syndrome Down syndrome Hydrocephalus Microcephaly Neonatal intraventricular hemorrhage with encephalopathy and cerebral palsy Agenesis of corpus callosum Chromosome 13 deletion Encephalopathy Herpes simplex encephalitis Inborn error of metabolism Sturge–Weber syndrome
7 7 2 2 2 2* 2
*Twin brothers.
1 1 1 1 1 1
Govindan et al 䡠 Incidence and Types of Childhood Exotropia Table 5. Causes of Sensory Exotropia among 17 Children Ocular Defect
n
Anisometropic amblyopia Bilateral (1) or unilateral (3) cataract Infectious corneal scar—HSV (1), VZV (1) Juxtafoveal chorioretinal scar Ocular albinism Persistent fetal vasculature Retinal detachment Retinal vascular disease (unilateral) Unilateral corneal leukoma
5 4 2 1 1 1 1 1 1
HSV ⫽ herpes simplex virus; VZV ⫽ varicella–zoster virus.
tive incidence of exotropia found in the current study for children younger than 3 years was 0.25%, similar to the findings of Friedman et al. The vast majority of prevalence studies of strabismus focus on children in the first year of primary school, with the prevalence varying from 0.43% to 1.7%.3,4,6,8 Nordlow reported the lowest rate, 0.43%, based on a screening of 6004 6-year-old school children in Vanersborg, Sweden.4 The screening, however, excluded children with paralytic strabismus and was performed by a nurse or general practitioner, who may have underestimated the true prevalence. The report by Graham, one of the most oft-quoted studies on strabismus, found an exotropia prevalence of 0.60% among 4784 grade-school children.3 He relied on a research orthoptist to identify and screen 99% of all children born during a single year in Cardiff, Wales, some of whom were invited for a more comprehensive evaluation. Our cumulative incidence of 0.61% for patients between birth and 6 years in Olmsted County is nearly identical to the 0.60% prevalence rate reported by Graham. A recent report by Chew et al found a prevalence of 1.2% among 39 227 7-year-olds born in any 1 of 12 urban university medical centers.8 The study suffers, however, from the dual weaknesses of study center referral bias and an examination by the primary care physician. The highest prevalence (1.7%) among 6-year-old children was reported by Kornder et al who, as in their study of preverbal children,5 focused their screening on those with a family history of strabismus.6 Perhaps the most comprehensive but inaccessible report on childhood strabismus is by Frandsen, who reported on a selected screening of 16 046 children between birth and 19 years.2 Frandsen reported an incidence of 1.27% of exotropia based on a screening of nurseries, schools, and “mental institutions” in Copenhagen during the 1950s.2 Although the author examined the patients herself, the study was not a population-based effort. However, the cumulative incidence of childhood exotropia estimated from our study on children from birth through 18 years was 1.25%, nearly identical to the findings of Frandsen. This study also reports the relative incidence of the various types of childhood exotropia. Whereas some studies make no distinction between the various forms and simply describe exotropia as a whole,2,5,6,8 others merely separate the intermittent variety from the constant.3,4,7 There are
only 2 known studies in English describing the individual forms of childhood exotropia, although neither is population based or provides an estimate of incidence.11,12 The first, by Fletcher and Silverman, describes 203 Houston patients of unknown ages with intermittent exotropia comprising 81.3%, 14 (6.9%) with either a sensory or a CNS defect, 8 with a paralytic etiology, and 7 with convergence insufficiency.12 A recent study of children younger than 19 years in a predominantly rural region of the United States, utilizing similar definitions to classify the various forms, found types and their corresponding percentages very similar to those of the present study, except that exotropic children with an abnormal CNS were the second most common form, as opposed to convergence insufficiency in the current study.11 Although intermittent exotropia seems to be the most prevalent form of exotropia, convergence insufficiency, which is likely to be underestimated in this and prior studies due to its vague symptomatology and imperceptible nature, may be nearly as common. Although this study reports a population-based incidence for childhood exotropia, it is not without limitations. Patients with an intermittent or small angle of deviation may have gone unnoticed by the caretaker, thereby avoiding evaluation by the study ophthalmologists and artificially decreasing the incidence in this population. A second potential weakness was the inability to review the medical records of optometrists practicing within the study region. Although a cursory review of their charts confirmed that they rarely evaluated pediatric patients with strabismus, failing to identify all patients with exotropia would underestimate its incidence in this population. Additionally, some residents of this population may have sought care outside Olmsted County, although we estimate these numbers to be a very small source of error. Another source of potential underestimation of the incidence of exotropia was our inability to evaluate exhaustively all comorbid disorders in our search for cases of secondary exotropia. Finally, 4% of the medical records were not available for review because the patients or their families refused research authorization. Because the ethnic composition of Olmsted County is over 90% white, our results are best extrapolated to the semiurban white population of the U.S. Nevertheless, the prevalence of exotropia among blacks has been reported to be nearly identical to that of whites from similar urban populations.8 Less is known regarding the prevalence of strabismus for other ethnic populations. Recognizing these weaknesses and assuming a population of 67 224 000 citizens younger than 19 years of age (1990 U.S. census), we estimate 43 103 new cases of childhood exotropia each year in the United States. Approximately one half of these will presumably develop the most common form, intermittent exotropia. The incidence of childhood exotropia derived from this population-based study is similar to prior studies of prevalence. We found a cumulative incidence of approximately 1.0% for all children younger than 11 years. Intermittent exotropia, convergence insufficiency, and exotropia in the setting of an abnormal CNS were the most commonly diagnosed forms in this population.
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References 1. Yu CB, Fan DS, Wong VW, et al. Changing patterns of strabismus: a decade of experience in Hong Kong. Br J Ophthalmol 2002;86:854 – 6. 2. Frandsen AD. Occurrence of squint: a clinical-statistical study on the prevalence of squint and associated signs in different groups and ages of the Danish population. Acta Ophthalmol Suppl 1960;62:9 –157. 3. Graham PA. Epidemiology of strabismus. Br J Ophthalmol 1974;58:224 –31. 4. Nordlow W. Squint—the frequency of onset at different ages, and the incidence of some associated defects in a Swedish population. Acta Ophthalmol (Copenh) 1964;42:1015–37. 5. Kornder LD, Nursey JN, Pratt-Johnson JA, Beattie A. Detection of manifest strabismus in young children. 1. A prospective study. Am J Ophthalmol 1974;77:207–10.
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6. Kornder LD, Nursey JN, Pratt-Johnson JA, Beattie A. Detection of manifest strabismus in young children. 2. A retrospective study. Am J Ophthalmol 1974;77:211– 4. 7. Friedman Z, Neumann E, Hyams SW, Peleg B. Ophthalmic screening of 38,000 children, age 1 to 2 1/2 years, in child welfare clinics. J Pediatr Ophthalmol Strabismus 1980;17: 261–7. 8. Chew E, Remaley NA, Tamboli A, et al. Risk factors for esotropia and exotropia. Arch Ophthalmol 1994;112:1349 –55. 9. Kurland LT, Molgaard CA. The patient record in epidemiology. Sci Am 1981;245:54 – 63. 10. Melton LJ III. History of the Rochester Epidemiology Project. Mayo Clin Proc 1996;71:266 –74. 11. Mohney BG, Huffaker RK. Common forms of childhood exotropia. Ophthalmology 2003;110:2093– 6. 12. Fletcher MC, Silverman SJ. Strabismus. I. A summary of 1,110 consecutive cases. Am J Ophthalmol 1966;61:86 –94.
Exotropia is a disorder of ocular alignment characterized by an outward deviation of the eyes. Although recently reported to occur more frequently than esotropia in Asians,1 exodeviations are much less common than esodeviations among Western populations.2,3 However, existing epidemiologic reports of childhood exotropia predominantly rely on mass screenings of variable populations, often by nonophthalmic specialists, and provide little information on the true population-based incidence of this disorder.2– 8 Populationbased data on the incidence and specific forms of exotropia, each with its own epidemiologic profile, would be useful in the allocation of health care resources and the development of clinical trials. The primary objective of this study was to determine the incidence and types of exotropia among pa-
Originally received: March 29, 2004. Accepted: July 23, 2004. Manuscript no. 240233. 1 Mayo Clinic College of Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. 2 Department of Ophthalmology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. 3 Division of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. 4 Division of Epidemiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. Correspondence to Brian G. Mohney, MD, Mayo Clinic, Department of Ophthalmology, 200 First Street Southwest, Rochester, MN 55905. E-mail: [email protected].
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© 2005 by the American Academy of Ophthalmology Published by Elsevier Inc.
tients younger than 19 years diagnosed during a 10-year period using a population-based medical record retrieval system.
Subjects and Methods The medical records of all patients younger than 19 years who were residing in Olmsted County, Minnesota and diagnosed with exotropia from January 1, 1985 through December 31, 1994 were retrospectively reviewed. Potential cases of exotropia were identified by using the resources of the Rochester Epidemiology Project, a medical records linkage system designed to capture data on any patient–physician encounter in Olmsted County, Minnesota.9,10 The population of this upper Midwest community of the United States (106 470 in 1990) is relatively isolated from other urban areas, and virtually all medical care is provided to county residents by Mayo Clinic or Olmsted Medical Group and their affiliated hospitals. Institutional review board approval was obtained for this study. We reviewed the medical records of all patients 0 through 18 years of age who were diagnosed by an ophthalmologist as having exotropia, hypertropia, or an unspecified strabismus from 1984 through 1999. We also reviewed the records of pediatric patients who were, during the same interval, diagnosed with cranial nerve palsies, retinal disorders, cataract, corneal scarring, optic nerve disorders, and developmental delay to avoid missing any potential cases of secondary exotropia. All diagnoses are entered into the Rochester Epidemiology Project database by trained personnel who review the entire medical record. There were 2 to 3 active optometric practices within Olmsted County during the time of this study. However, these practices uncommonly evaluated pediatric patients; a recent computer search of exotropic patients examined ISSN 0161-6420/05/$–see front matter doi:10.1016/j.ophtha.2004.07.033
Govindan et al 䡠 Incidence and Types of Childhood Exotropia Table 1. Incidence of Childhood Exotropia in Olmsted County, Minnesota, 1985 to 1994
Age Group (yrs) 0–1 2–3 4–5 6–7 8–9 10–11 12–13 14–15 16–17 18 Total Age/gender adjusted total
Female Incidence Rates (per 100 000 Patients Younger than 19)
Male Incidence Rates (per 100 000 Patients Younger than 19)
Total Incidence Rates (per 100 000 Patients Younger than 19)
58.0 142.0 81.4 102.0 142.3 49.8 54.9 28.1 6.8 30.5 74.2
61.3 79.4 49.2 79.2 84.8 52.3 33.2 51.9 34.8 44.0 58.8
59.7 110.7 64.8 90.3 112.3 51.1 43.9 40.5 20.7 37.4 66.3 64.1
during a 4-year period (January 1, 2000 –December 31, 2003) by one 3-person practice yielded 5 exotropic patients, only 1 of whom was younger than 19. Trained residency checkers verified patients’ residency status at the time of birth and at diagnosis using information from city and county directories. Patients not residing in Olmsted County at the time of their diagnosis were excluded. Sixty-six (3.94%) of the 1672 potential patients refused research authorization, and their medical records were not reviewed. The ophthalmic records of the remaining 1606 potential cases were reviewed. Except for those with convergence insufficiency or a paralytic deviation, all patients diagnosed with an intermittent or constant exotropia of ⱖ10 prism diopters (PD; at either distance or near in the primary position) during the study period were included. The angle of deviation was measured by the prism and alternative cover technique at both distance and near for most patients, although the Krimsky prism technique was necessary in infants, some young children, and those with neurologic deficits. Patients with convergence insufficiency were enrolled if they were symptomatic and displayed a near deviation of ⱖ4 PD, or asymptomatic with a deviation of ⱖ10 PD, with most being orthotropic in the distance. Two of the 8 children with paralytic strabismus (e.g., Duane’s type II or type III retraction syndrome or third cranial nerve palsy) displayed ⬍10 PD of exotropia in the primary position but, because their strabismus predominantly resulted in an exotropic deviation, were included in the study. The entire medical record of those diagnosed with exotropia was carefully reviewed for any developmental, neurologic, or ocular disorder that might have caused or been associated with the exotropic deviation. The following criteria were used to classify the various types of childhood exotropia.11 Intermittent exotropia was defined as an acquired deviation that was either intermittent or, if constant, not associated with dissociated strabismus and demonstrated 50 arc seconds or better of stereopsis either before or after strabismus surgery. Congenital exotropia included neurologically intact children with a constant deviation that developed by 6 months of age. Exotropic children with a congenital or acquired developmental or neurologic disorder were grouped under central nervous system (CNS) defects regardless of the age at onset. Because it was impossible to correlate CNS disease severity with the development of strabismus, any form of neurologic impairment except isolated speech delay was included in this category. Sensory exotropia included patients with a unilateral or bilateral ocular condition that prevented normal fusion. Postoperative consecutive exotropia was not included in this series because it is not a naturally occurring form of strabismus. No patient was placed in more than one diagnostic group. Annual age- and gender-specific incidence rates were con-
structed using the age- and gender-specific population figures for Olmsted County, Minnesota from the United States census. Ageand gender-specific denominators for individual years were generated from linear interpolation of the 1970, 1980, 1990, and 2000 census figures. The 95% confidence intervals (CIs) were calculated with assumptions based on the Poisson distribution. Trends over time, by age, and between genders were investigated using Poisson regression models.
Results Two hundred five new cases of childhood exotropia were identified in Olmsted County, Minnesota during the 10-year study period. There were 112 female (54.6%) and 93 male (45.4%) incident cases. The age- and gender- adjusted annual incidence rate for exotropia was 64.1/100 000 patients younger than 19 years (Table 1), with a significant decrease in the second decade of life (P⬍0.001). There was a bimodal peak in diagnosis at approximately 3 years of age and again at 9 years. The overall ageadjusted incidence among girls (71.0/100 000) was slightly greater than that among boys (57.5/100 000). Girls tended to be more likely than boys to develop exotropia during the first decade, whereas boys were more commonly exotropic during the teenage years (P ⫽ 0.10), as shown in Figure 1. Numbers of children diagnosed with exotropia were similar throughout the 10-year period. Table 2 shows the cumulative incidence rates by age calculated from our incidence data. Although the cumulative incidence steadily increases through age 18, the vast majority of patients were diagnosed by age 10, corresponding to a prevalence of approximately 1.0%. The additive nature of Table 2 assumes no spontaneous resolution of the exotropias diagnosed in this study. Table 3 shows the relative frequencies and incidence rates for the various types of childhood exotropia. Intermittent exotropia was the most frequently diagnosed form of exotropia, comprising 51.7% of all study patients, with an incidence rate of 32.1/100 000 patients younger than 19 years. Convergence insufficiency was found in 40 children (19.5%), corresponding to an incidence of 13.7/100 000. The specific CNS defects associated with 30 of the exotropic children are shown in Table 4, whereas the causes of sensory exotropia in the 17 children with this condition are shown in Table 5. Paralytic (8), congenital (1), and the undetermined (3) forms of exotropia had a combined incidence rate of 3.9/100 000 patients younger than 19.
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Ophthalmology Volume 112, Number 1, January 2005 Table 3. Observed Types of Exotropia among 205 Consecutive Patients Younger than 19 Years in Olmsted County, Minnesota, 1985 to 1994
Figure 1. Incidence rates of childhood exotropia by age in Olmsted County, Minnesota, 1985 to 1994 (3-year running average).
Discussion This study provides data on the incidence of childhood exotropia in a geographically defined population. We found an annual age- and gender-adjusted incidence of 64.1 (95% CI: 55.2–72.9)/100 000 patients younger than 19 years. The incidence rate was highest in the first decade of life, with a prevalence or cumulative incidence of 1.0%. New cases of exotropia significantly decreased in the second decade of life. Although girls were more likely than boys to be diagnosed with exotropia, there was no significant difference between the genders, nor was there a significant change in the incidence rate over the 10-year study period. Published studies on the prevalence of strabismus have included preverbal children,5,7 children 6 to 7 years old,3,4,6,8 and a more comprehensive review of children between birth and 19 years.2 However, these studies were Table 2. Cumulative Incidence of Childhood Exotropia in Olmsted County, Minnesota, 1985 to 1994 Age Group (yrs) 0–2 0–3 0–4 0–5 0–6 0–7 0–8 0–9 0–10 0–11 0–12 0–13 0–14 0–15 0–16 0–17 0–18
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Cumulative Incidence (%)
Cumulative n
0.25 0.37 0.40 0.51 0.61 0.69 0.79 0.92 0.98 1.03 1.08 1.11 1.15 1.18 1.21 1.22 1.25
41 60 66 83 101 114 130 152 161 169 178 182 189 194 198 200 205
Exotropia Type
n
%
Intermittent* Convergence insufficiency Abnormal central nervous system Sensory Paralytic Congenital Other (undetermined)
106 40 30 17 8 1 3
51.7 19.5 14.6 8.25 3.9 0.5 1.5
Incidence per 100 000 Patients Younger than 19 (CI) 32.1 (25.9–38.2) 13.7 (9.5–18.0) 9.1 (5.9–12.4) 5.3 (2.7–7.8) † † †
CI ⫽ age- and gender-adjusted 95% confidence interval. *One had a constant deviation at presentation. † The combined incidence rate of the paralytic, congenital, and undetermined forms of exotropia was 3.9 (1.7– 6.1, CI) per 100 000 patients younger than 19.
comprised of mass screenings of selected children and were not population-based efforts. Moreover, most were performed exclusively by orthoptists or specially trained nurses and were not commonly performed or confirmed by an ophthalmologist. Despite these limitations, the prevalence rates from these reports may be compared with the cumulative incidence values calculated from this study (Table 2) by adjusting for the age at which the prior studies were conducted. Two reports have described the prevalence of strabismus among preverbal children.5,7 Kornder et al reported an exotropia prevalence of 1.0% among 1074 children from 6 to 30 months of age.5 Friedman et al, reporting on 38 000 similarly aged children, found exotropia to occur in only 0.30%.7 Kornder et al’s prevalence estimate of ⬎3 times that of Friedman et al is likely due to the former’s screening of children from high-risk families (positive family history) as identified by a prescreening questionnaire. The cumulaTable 4. Disorders Contributing to Documented Central Nervous System (CNS) Impairment among 30 Children with Exotropia CNS Disorder
n
Cerebral palsy Developmental delay Crouzon’s syndrome Down syndrome Hydrocephalus Microcephaly Neonatal intraventricular hemorrhage with encephalopathy and cerebral palsy Agenesis of corpus callosum Chromosome 13 deletion Encephalopathy Herpes simplex encephalitis Inborn error of metabolism Sturge–Weber syndrome
7 7 2 2 2 2* 2
*Twin brothers.
1 1 1 1 1 1
Govindan et al 䡠 Incidence and Types of Childhood Exotropia Table 5. Causes of Sensory Exotropia among 17 Children Ocular Defect
n
Anisometropic amblyopia Bilateral (1) or unilateral (3) cataract Infectious corneal scar—HSV (1), VZV (1) Juxtafoveal chorioretinal scar Ocular albinism Persistent fetal vasculature Retinal detachment Retinal vascular disease (unilateral) Unilateral corneal leukoma
5 4 2 1 1 1 1 1 1
HSV ⫽ herpes simplex virus; VZV ⫽ varicella–zoster virus.
tive incidence of exotropia found in the current study for children younger than 3 years was 0.25%, similar to the findings of Friedman et al. The vast majority of prevalence studies of strabismus focus on children in the first year of primary school, with the prevalence varying from 0.43% to 1.7%.3,4,6,8 Nordlow reported the lowest rate, 0.43%, based on a screening of 6004 6-year-old school children in Vanersborg, Sweden.4 The screening, however, excluded children with paralytic strabismus and was performed by a nurse or general practitioner, who may have underestimated the true prevalence. The report by Graham, one of the most oft-quoted studies on strabismus, found an exotropia prevalence of 0.60% among 4784 grade-school children.3 He relied on a research orthoptist to identify and screen 99% of all children born during a single year in Cardiff, Wales, some of whom were invited for a more comprehensive evaluation. Our cumulative incidence of 0.61% for patients between birth and 6 years in Olmsted County is nearly identical to the 0.60% prevalence rate reported by Graham. A recent report by Chew et al found a prevalence of 1.2% among 39 227 7-year-olds born in any 1 of 12 urban university medical centers.8 The study suffers, however, from the dual weaknesses of study center referral bias and an examination by the primary care physician. The highest prevalence (1.7%) among 6-year-old children was reported by Kornder et al who, as in their study of preverbal children,5 focused their screening on those with a family history of strabismus.6 Perhaps the most comprehensive but inaccessible report on childhood strabismus is by Frandsen, who reported on a selected screening of 16 046 children between birth and 19 years.2 Frandsen reported an incidence of 1.27% of exotropia based on a screening of nurseries, schools, and “mental institutions” in Copenhagen during the 1950s.2 Although the author examined the patients herself, the study was not a population-based effort. However, the cumulative incidence of childhood exotropia estimated from our study on children from birth through 18 years was 1.25%, nearly identical to the findings of Frandsen. This study also reports the relative incidence of the various types of childhood exotropia. Whereas some studies make no distinction between the various forms and simply describe exotropia as a whole,2,5,6,8 others merely separate the intermittent variety from the constant.3,4,7 There are
only 2 known studies in English describing the individual forms of childhood exotropia, although neither is population based or provides an estimate of incidence.11,12 The first, by Fletcher and Silverman, describes 203 Houston patients of unknown ages with intermittent exotropia comprising 81.3%, 14 (6.9%) with either a sensory or a CNS defect, 8 with a paralytic etiology, and 7 with convergence insufficiency.12 A recent study of children younger than 19 years in a predominantly rural region of the United States, utilizing similar definitions to classify the various forms, found types and their corresponding percentages very similar to those of the present study, except that exotropic children with an abnormal CNS were the second most common form, as opposed to convergence insufficiency in the current study.11 Although intermittent exotropia seems to be the most prevalent form of exotropia, convergence insufficiency, which is likely to be underestimated in this and prior studies due to its vague symptomatology and imperceptible nature, may be nearly as common. Although this study reports a population-based incidence for childhood exotropia, it is not without limitations. Patients with an intermittent or small angle of deviation may have gone unnoticed by the caretaker, thereby avoiding evaluation by the study ophthalmologists and artificially decreasing the incidence in this population. A second potential weakness was the inability to review the medical records of optometrists practicing within the study region. Although a cursory review of their charts confirmed that they rarely evaluated pediatric patients with strabismus, failing to identify all patients with exotropia would underestimate its incidence in this population. Additionally, some residents of this population may have sought care outside Olmsted County, although we estimate these numbers to be a very small source of error. Another source of potential underestimation of the incidence of exotropia was our inability to evaluate exhaustively all comorbid disorders in our search for cases of secondary exotropia. Finally, 4% of the medical records were not available for review because the patients or their families refused research authorization. Because the ethnic composition of Olmsted County is over 90% white, our results are best extrapolated to the semiurban white population of the U.S. Nevertheless, the prevalence of exotropia among blacks has been reported to be nearly identical to that of whites from similar urban populations.8 Less is known regarding the prevalence of strabismus for other ethnic populations. Recognizing these weaknesses and assuming a population of 67 224 000 citizens younger than 19 years of age (1990 U.S. census), we estimate 43 103 new cases of childhood exotropia each year in the United States. Approximately one half of these will presumably develop the most common form, intermittent exotropia. The incidence of childhood exotropia derived from this population-based study is similar to prior studies of prevalence. We found a cumulative incidence of approximately 1.0% for all children younger than 11 years. Intermittent exotropia, convergence insufficiency, and exotropia in the setting of an abnormal CNS were the most commonly diagnosed forms in this population.
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References 1. Yu CB, Fan DS, Wong VW, et al. Changing patterns of strabismus: a decade of experience in Hong Kong. Br J Ophthalmol 2002;86:854 – 6. 2. Frandsen AD. Occurrence of squint: a clinical-statistical study on the prevalence of squint and associated signs in different groups and ages of the Danish population. Acta Ophthalmol Suppl 1960;62:9 –157. 3. Graham PA. Epidemiology of strabismus. Br J Ophthalmol 1974;58:224 –31. 4. Nordlow W. Squint—the frequency of onset at different ages, and the incidence of some associated defects in a Swedish population. Acta Ophthalmol (Copenh) 1964;42:1015–37. 5. Kornder LD, Nursey JN, Pratt-Johnson JA, Beattie A. Detection of manifest strabismus in young children. 1. A prospective study. Am J Ophthalmol 1974;77:207–10.
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6. Kornder LD, Nursey JN, Pratt-Johnson JA, Beattie A. Detection of manifest strabismus in young children. 2. A retrospective study. Am J Ophthalmol 1974;77:211– 4. 7. Friedman Z, Neumann E, Hyams SW, Peleg B. Ophthalmic screening of 38,000 children, age 1 to 2 1/2 years, in child welfare clinics. J Pediatr Ophthalmol Strabismus 1980;17: 261–7. 8. Chew E, Remaley NA, Tamboli A, et al. Risk factors for esotropia and exotropia. Arch Ophthalmol 1994;112:1349 –55. 9. Kurland LT, Molgaard CA. The patient record in epidemiology. Sci Am 1981;245:54 – 63. 10. Melton LJ III. History of the Rochester Epidemiology Project. Mayo Clin Proc 1996;71:266 –74. 11. Mohney BG, Huffaker RK. Common forms of childhood exotropia. Ophthalmology 2003;110:2093– 6. 12. Fletcher MC, Silverman SJ. Strabismus. I. A summary of 1,110 consecutive cases. Am J Ophthalmol 1966;61:86 –94.