Clinical Context

Strabismus affects 2% to 5% of US children and has been associated with higher rates of disability and reduced quality of life. But does corrective surgery for strabismus change these associations? Archer and colleagues performed a prospective cohort study to answer this question; their results were published in the April 2005 issue of the Journal of the American Association for Pediatric Ophthalmology and Strabismus.^[1]

Parents of 98 children with a mean age of 4.5 years were asked to complete a quality-of-life instrument both before corrective surgery for strabismus and then 2 months postoperatively. Overall, there was good internal consistency within children completing the survey. Surgery was associated with improvements across nearly all domains of quality of life, including functional limitations, social relations, and general health perception. Interestingly, 1 of the 2 variables that was not improved with surgery was positive well-being.

Previous research has suggested that strabismus may be associated with a higher rate of mental illness, but these studies focused on smaller populations in specific locations. The current study takes a broader look at mental illness among children with strabismus.

Study Synopsis and Perspective

Misaligned eyes in children are associated with an increased prevalence of mental illness, results of a large study suggest.

Investigators found that children with strabismus or "crossed eyes" had up to a 2-fold increased risk of developing anxiety, depression, bipolar disorder, and schizophrenia compared with their counterparts without the eye condition.

"Psychiatrists who have a patient with depression or anxiety and notice that patient also has strabismus might think about the link between those 2 conditions and refer that patient," study investigator Stacy L. Pineles, MD, professor, Department of Ophthalmology, University of California at Los Angeles, told Medscape Medical News.

The study was published online March 10 in JAMA Ophthalmology.^[2]

Strabismus, a condition in which the eyes do not line up or are "crossed," is one of the most common eye diseases in children, with some estimates suggesting that it affects more than 1.5 million American youth.

Patients with strabismus have problems making eye contact and are affected socially and functionally, said Dr Pineles. They are often met with a negative bias, as shown by children's responses to pictures of faces with and without strabismus, she said.

There is a signal from previous research suggesting that strabismus is linked to a higher risk for mental illness. However, most of these studies were small and had relatively homogenous populations, said Dr Pineles.

The new study includes more than 12 million children (mean age, 8.0 years) from a private health insurance claims database that represents diverse races and ethnicities as well as geographic regions across the United States.

The sample included 352,636 children with strabismus and 11,652,553 children with no diagnosed eye disease who served as controls. Most participants were White (51.6%), came from a family with an annual household income of $40,000 or more (51.0%), had point-of-service insurance (68.7%), and had at least 1 comorbid condition (64.5%).

The study evaluated 5 mental illness diagnoses. These included anxiety disorder, depressive disorder, substance use or addictive disorder, bipolar disorder, and schizophrenia.

Overall, children with strabismus had a higher prevalence of all these illnesses with the exception of substance use disorder.

After adjusting for age, sex, race and ethnicity, census region, education level of caregiver, family net worth, and presence of at least 1 comorbid condition, the odds ratios (ORs) among those with versus without strabismus were 2.01 (95% confidence interval [CI], 1.99-2.04; P<.001) for anxiety disorder, 1.83 (95% CI, 1.76-1.90; P<.001) for schizophrenia, 1.64 (95% CI, 1.59-1.70; P<.001) for bipolar disorder, and 1.61 (95% CI, 1.59-1.63; P<.001) for depressive disorder.

Substance use disorder had a negative unadjusted association with strabismus, but after adjustment for confounders, the association was not significant (OR, 0.99; 95% CI, 0.97-1.02; P=.48).

Dr Pineles noted that the study participants, who were all younger than 19 years, may be too young to have substance use disorders.

The results for substance use disorders provided something of an "internal control" and reaffirmed results for the other 4 conditions, said Dr Pineles.

"When you do research on such a large database, you're very likely to find significant associations; the data set is so large that even very small differences become statistically significant. It was interesting that not everything gave us a positive association."

Researchers divided the strabismus group into those with esotropia, where the eyes turn inward (52.2%); exotropia, where they turn outward (46.3%); and hypertropia, where 1 eye wanders upward (12.5%). Investigators found that all 3 conditions were associated with increased risk for anxiety disorder, depressive disorder, bipolar disorders, and schizophrenia.

The investigators note that rates in the current study were lower than in previous studies, which showed that children with congenital esotropia were 2.6 times more likely to receive a mental health diagnosis and children with intermittent exotropia were 2.7 times more likely to receive a mental health diagnosis.

"It is probable that our study found a lower risk than these studies because our study was cross-sectional and claims based, whereas these studies observed the children to early adulthood and were based on medical records," the investigators note.

It is impossible to determine from this study how strabismus is connected to mental illness. However, Dr Pineles believes that depression and anxiety might be tied to strabismus via teasing, which affects self-esteem, although genetics could also play a role. For conditions such as schizophrenia, a shared genetic link with strabismus might be more likely, she added.

"Schizophrenia is a pretty severe diagnosis, so just being teased or having poor self-esteem is probably not enough" to develop schizophrenia.

Based on her clinical experience, Dr Pineles said that realigning the eyes of patients with milder forms of depression or anxiety "definitely anecdotally helps these patients a lot."

Dr Pineles and colleagues have another paper in press that examines mental illnesses and other serious eye disorders in children and shows similar findings, she said.

In an accompanying editorial, experts led by S. Grace Prakalapakorn, MD, from the Department of Ophthalmology and Pediatrics, Duke University Medical Center, Durham, North Carolina, noted the exclusion of children covered under government insurance or without insurance is an important study limitation, largely because socioeconomic status is a risk factor for poor mental health.^[3]

The editorialists point to studies showing that surgical correction of ocular misalignments may be associated with reduced anxiety and depression. However, health insurance coverage for such surgical correction "may not be available owing to a misconception that these conditions are 'cosmetic,' " they note.

Evidence of the broader association of strabismus with physical and mental health "may play an important role in shifting policy to promote insurance coverage for timely strabismus care," they write.

As many mental health disorders begin in childhood or adolescence, "it is paramount to identify, address, and, if possible, prevent mental health disorders at a young age because failure to intervene in a timely fashion can have lifelong health consequences," conclude Dr Prakalapakorn and colleagues.

With mental health conditions and disorders increasing worldwide, compounded by the stressors of the COVID-19 pandemic, additional studies are needed to explore the causal relationships between ocular and psychiatric phenomena, their treatment, and outcomes, they add.

The study was supported by a grant from the National Eye Institute and an unrestricted grant from Research to Prevent Blindness. Dr Pineles has reported no relevant conflicts of interest. Commentary author Manpreet K. Singh, MD, has reported receiving research support from Stanford's Maternal Child Health Research Institute and Stanford's Department of Psychiatry and Behavioral Sciences, the National Institute of Mental Health, the National Institute on Aging, the Patient-Centered Outcomes Research Institute, Johnson & Johnson, Allergan, and the Brain and Behavior Research Foundation; serving on the advisory board for Sunovion and Skyland Trail; serving as a consultant for Johnson & Johnson; previously serving as a consultant for X, the moonshot factory, Alphabet, and Limbix Health; receiving honoraria from the American Academy of Child and Adolescent Psychiatry; and receiving royalties from American Psychiatric Association Publishing and Thrive Global. Commentary author Nathan Congdon, MD, has reported receiving personal fees from Belkin Vision outside the submitted work.

JAMA Ophthalmol. Published online March 10, 2022.

Clinical Implications

• In a previous study of corrective surgery among children with strabismus, surgery was associated with improvements across nearly all domains of quality of life, including functional limitations, social relations, and general health perception. However, one variable that was not improved with surgery was positive well-being.
• In the current study, strabismus among children was associated with higher rates of anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder. Strabismus did not affect the rate of substance use disorders.
• Outline implications for the healthcare team: The healthcare team should monitor the mental health of children with strabismus and promptly intervene if symptoms arise. The cross-sectional study by Lee et. al., suggests that “there was a moderate association between strabismus and anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder but not substance use disorder” ^[2]. The healthcare team should recognize these associations and monitor mental illness screening and treatment for children and patients with strabismus.

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