Horizontal Strabismus Worldwide – What Are The Risk Factors?

Abstract

Horizontal strabismus has constant risk factors of ethnicity, family history, genetic conditions and potentially modifiable risk factors of maternal smoking, prematurity, low birth weight, refractive errors and neurodisability.

Keywords::

• Prevalence
• strabismus
• refractive errors,
• pediatric ophthalmology,
• epidemiology

The previous issue of this journal contains a paper from Cape Town, S. Africa by C. Tinley and R Grotte which expands the current limited knowledge about strabismus in African children¹. It was a retrospective clinic-based study from a state tertiary pediatric centre so did not include those attending the private health care sector (mainly white children and children from other ethnic backgrounds). The Western Cape population’s interesting ethnic mix provides natural clues about the genetic basis of strabismus. Their presenting clinic population consisted of mixed race and black race. The mixed race people are from two distinct origins: (1) Colored community descended from early intermarriages between European settlers and black natives. (2) Cape Malays have historical and genetic connections with ancestors from South-East Asia. The black people belong mainly to the Xhosa-speaking tribe. These groups exhibit different patterns of strabismus. Black children are affected by congenital esotropia (74%) more than accommodative esotropia (9%) and few have exotropia. Mixed race children have a more equal distribution between congenital esotropia (46%) and accommodative esotropia (35%). There was also a disproportionately lower number of strabismus cases in black children – 81% mixed race: 19% black race although the ethnic composition for Cape Town was 50% mixed race: 30% black race¹.

What do we currently know about risk factors for strabismus?

1. ETHNICITY

Population prevalence studies of strabismus have highlighted different rates for ethnic groups within countries. The Millennium Cohort Study from the United Kingdom found that children from non-white maternal ethnicity (African and Caribbean) were only one-fifth as likely to have isolated strabismus.² The Sydney Childhood Eye Study, Australia, found that children with non-white ethnicity were 3 times less likely to have esotropia than white children but that there was no difference for exotropia.³ The Baltimore Pediatric Eye Disease Study (BPEDS), USA found manifest strabismus in 3.3% of white and 2.1% of African American children.⁴ The Collaborative Perinatal Project (CPP) of the National Institute of Neurological Disorders and Stroke, Bethesda, USA showed that esotropia was more common in white than black children (3.9% in white vs 2.2% in black children) but that exotropia was similar in the two groups (1.2% in white vs 1.3% in black children).⁵ The Multi-Ethnic Pediatric Eye Disease Study (MEPEDS), USA found strabismus in 2.4% of Hispanic/Latino children and 2.5% of African American children.⁶

The MEPEDS and BPEDS showed that compared with non-Hispanic whites, African-American (odds ratio, OR, 6.0) and Hispanic children (OR 3.2) were more likely to be myopic. They also found that compared with African-American children, non-Hispanic white (OR 1.63) and Hispanic white (OR 1.49) were more likely to be hyperopic.⁷

2. REFRACTIVE ERROR

In the Sydney Childhood Eye Study children with strabismus were significantly more hyperopic than children without strabismus (mean spherical equivalent, SE, +2.46D vs +1.23D). They noted a higher prevalence of significant hyperopia (+3.00D or more) in white children (4.6%) than in non-white children (2.4%). The higher prevalence of esotropia among white children in their sample was thought to be due to a close link between accommodative esotropia and hyperopia.³ The MEPEDS and BPEDS showed that hyperopia of +3.00D or more was the strongest predictor of esotropia. There is an approximately linear relationship between prevalence of esotropia and spherical equivalent refractive error. The odds ratio for hyperopia in the range +2.00-<+3.00D is 6.38; the odds ratio for hyperopia in the range +3.00-<+4.00D is 23.06; the odds ratio for hyperopia in the range +4.00-<+5.00D is 59.81 and the odds ratio for hyperopia ≥+5.00D is 122.24. In other words, the odds of having esotropia are 122 times greater in those children with hyperopia of 5.00D or more than in children with 1.00D of hyperopia or less. With hyperopia of 5.00D or more, esotropia is seen in 24% of cases.⁸ The MEPEDS and BPEDS showed that astigmatism of 2.50D or more was the strongest predictor of exotropia, conferring a 6-fold risk. There is an approximately linear relationship between the prevalence of exotropia and the magnitude of astigmatism. The odds ratio for astigmatism in the range 1.50-<2.50D is 2.49; the odds ratio for astigmatism ≥2.50D is 5.88.⁸

The MEPEDS showed that strabismus was associated with both spherical anisometropia (OR 6.2 for esotropia; OR 3.52 for exotropia) and cylindrical (astigmatic) anisometropia (OR 3.02 for esotropia; OR 3.99 for exotropia.⁹

3. FAMILIAL HISTORY

In the CPP study the risk of additional siblings being affected was doubled for esotropia (OR 2.6) and if from a multiple birth the association was further increased (OR 5.4). For exotropia there was little evidence of an association between siblings from separate births but there was a strong association between siblings from multiple births which increased by a factor of 17.¹⁰ In the Olmstead County population a positive family history was associated with a 3.5-fold excess risk of developing congenital esotropia.¹¹

4. GENDER

The Singapore STAR Study,¹² the Sydney Childhood Eye Study,¹³ the Avon Longitudinal Study of Parents and Children (ALSPAC) UK,¹⁴ and the BPEDS,⁴ did not find any gender difference for strabismus. The MEPEDS and BPEDS found an association between female gender and exotropia (OR 1.62).⁸

5. PREMATURITY AND BIRTH WEIGHT

In a study of risk factors associated with congenital esotropia from Olmstead County, USA the following were deemed significant: (1) prematurity (less than 37 weeks gestation): OR 11.5, and (2) low Apgar scores at 1 minute: OR 4.3.¹¹ The Millennium Cohort Study from the United Kingdom identified being born by assisted delivery, low birth weight (<2500 g) and preterm delivery (<37 weeks) with an increased risk of isolated strabismus.¹ The ALSPAC study showed that the risk of convergent squint was related to prematurity (<37 weeks; OR 2.47) and that divergent squint was related to intra-uterine growth retardation (OR 4.31).¹⁴ The CPP study showed that the risk of strabismus increased with (1) low birth weight: for infants weighing 1500g compared to 4000 g at birth the odds ratios were 3.26 for esotropia and 4.01 for exotropia, and (2) maternal age: the odds ratio for mothers aged 30 to 34 years relative to that for mothers aged 20 to 24 years was 1.43.⁵ The MEPEDS and BPEDS showed that (1) esotropia was associated with prematurity (<33 weeks; OR 4.43), and (2) exotropia was associated with prematurity (<33 weeks; OR 2.48).⁸ The Sydney Childhood Eye Study reported that prematurity (<37 weeks) was associated with a 5-fold increase in the risk of esotropia.³

6. SOCIO-ECONOMIC STATUS

Back in 1973 P A Graham looked at the epidemiology of strabismus in Cardiff, Wales and did not find a link with social class.¹⁵ The Sydney Childhood Eye Study also did not find an association between strabismus and socioeconomic status: parental education, employment status or home ownership.³ However the Millennium Cohort Study identified lower socioeconomic status with an increased risk of isolated strabismus.²

7. MATERNAL SMOKING

The CPP study showed that the risk of strabismus increased with maternal cigarette smoking. For the offspring of those mothers who smoked more than 2 packets of cigarettes per day compared to those who did not smoke the odds ratios were 1.83 for esotropia and 2.32 for exotropia. The observed association of strabismus, both esotropia and exotropia, with maternal smoking was independent of the well known adverse effects of maternal smoking on birth weight.⁵ The MEPEDS and BPEDS showed that the odds ratio for esotropia associated with maternal smoking during pregnancy was 2.04 and for exotropia was 2.88.⁸ The likelihood of strabismus increased with the average daily number of cigarettes smoked by the pregnant mother.⁸ Maternal smoking has also been associated with hyperopia⁷ and astigmatism¹⁶ but by adjusting for refractive error smoking has been shown to be related independently to strabismus. The ALSPAC showed that divergent squint was related to maternal smoking in late pregnancy (OR 2.46).¹⁴

8. NEURODISABILITY

It is known that children with neuro-disability have an increased risk of developing strabismus. The CPP study showed an increased association between strabismus and the following: (1) neurological abnormalities (OR 3.03 for both esotropia and exotropia) (2) seizure states (OR 2.93 for esotropia; OR 3.28 for exotropia) (3) central nervous system and skeletal conditions (OR 5.04 for esotropia; OR 4.91 for exotropia).⁵ In a USA prospective consecutive observational case series, 17.2% of children presenting with esotropia were associated with abnormalities of the central nervous system, mainly cerebral palsy and developmental delay.¹⁷ In a USA retrospective consecutive observational case series, 21.3% of children presenting with exotropia were associated with abnormalities of the central nervous system, mainly cerebral palsy and developmental delay.¹⁸ The Millennium Cohort Study included a sub-group of ‘neurodevelopmental’ strabismus affecting children who had impaired developmental indicators. Of 26 children with reported cerebral palsy, 4 (15.4%) had strabismus, as did 3 of 10 children with Down’s syndrome (30%) and 5 of 55 with reported mental and behavioral disorders (9.1%).² A population-based longitudinal Norwegian study of 60 children with Down’s syndrome found that 25 (42%) had strabismus. There were 20 cases of acquired esotropia, of which 15 (75%) were associated with hypermetropia (mean SE + 4.3 + /-1.7D) and 17 (85%) with accommodation weakness.¹⁹

How can this knowledge about risk factors for strabismus be used?

Risk reduction strategies such as health promotion to highlight the strabismic effect of maternal smoking and efforts to prevent preterm labor may reduce the incidence of strabismus. Case identification of those children at a higher risk of developing strabismus combined with early refractive assessment and monitoring may enable earlier detection of strabismus.

Declaration of interest: The author reports no conflict of interest.