Research

JAMA Ophthalmology | Brief Report

Mental Health Conditions Associated With Strabismus

in a Diverse Cohort of US Adults
Kimberly Jin, BS; Inas F. Aboobakar, MD; Mary C. Whitman, MD, PhD; Isdin Oke, MD, MPH

Supplemental content
IMPORTANCE Greater understanding of the association between strabismus and mental
health conditions across sociodemographic backgrounds may inform strategies to improve
mental well-being in this population.

OBJECTIVE To describe the association of strabismus with mental health conditions in a

diverse cohort of US adults.

DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used data from the National
Institutes of Health’s All of Us Research Program, an ongoing program launched in 2015. The
study included 3646 adults (aged ⱖ18 years) with strabismus and 3646 propensity
score–matched controls. Statistical analysis was conducted from September 12, 2023, to
January 29, 2024.

MAIN OUTCOMES AND MEASURES Adults with strabismus were propensity score matched on
age, gender, race and ethnicity, income, educational level, and insurance status in a 1:1 ratio
with adults without strabismus. The prevalences of anxiety, depression, substance use and
addiction, bipolar disorder, and schizophrenia spectrum disorder among adults with
strabismus were compared with controls. Logistic regression was used to evaluate the
association of mental health conditions with sociodemographic factors in each group.

RESULTS This study included 3646 adults with strabismus (median age, 67 years [IQR, 53-76
years]; 2017 women [55%]) and 3646 propensity score–matched controls (median age, 67
years [IQR, 53-76 years]; 2017 women [55%]). Individuals with strabismus had higher
prevalences of anxiety (1153 [32%] vs 519 [14%]; difference, 17%; 95% CI, 15%-19%; P < .001),
depression (1189 [33%] vs 514 [14%]; difference, 19%; 95% CI, 17%-20%; P < .001),
substance use and addiction (116 [3%] vs 51 [1%]; difference, 2%; 95% CI, 1%-3%; P < .001),
bipolar disorder (253 [7%] vs 101 [3%]; difference, 4%; 95% CI, 3%-5%; P < .001), and
schizophrenia spectrum disorder (103 [3%] vs 36 [1%]; difference, 2%; 95% CI, 1%-3%;
P < .001) compared with individuals without strabismus. Among adults with strabismus,
higher odds of mental health conditions were associated with younger age (odds ratio [OR],
1.11 per 10-year decrease; 95% CI, 1.06-1.16 per 10-year decrease), female gender (OR, 1.62;
95% CI, 1.41-1.85), Black or African American race and ethnicity (OR, 1.22; 95% CI, 1.01-1.48),
low income (OR, 3.06; 95% CI, 2.56-3.67), and high school education or less (OR, 1.58; 95%
CI, 1.34-1.85).

CONCLUSIONS AND RELEVANCE In a diverse and nationwide cohort, adults with strabismus
were more likely to have mental health conditions compared with adults without strabismus.
Further investigation into the risk factors for poor mental health among adults with
strabismus across sociodemographic backgrounds may offer novel opportunities for
Author Affiliations: University of
interventions to improve mental well-being in this population.
Massachusetts Chan School of
Medicine, Worcester (Jin);
Department of Ophthalmology,
Massachusetts Eye and Ear and
Harvard Medical School, Boston
(Aboobakar, Whitman, Oke);
Department of Ophthalmology,
Boston Children’s Hospital and
Harvard Medical School, Boston,
Massachusetts (Whitman, Oke).
Corresponding Author: Isdin Oke,
MD, MPH, Department of
Ophthalmology, Boston Children’s
Hospital, 300 Longwood Ave,
JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2024.0540 Boston, MA 02115 (isdin.oke@
Published online April 4, 2024. childrens.harvard.edu).

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 Research Brief Report
A
pproximately 2% to 3% of individuals in the US have
strabismus,1 a condition that may negatively affect psy-
chosocial well-being and predispose individuals to
mental health conditions, such as anxiety and depression.2
Limited research exists on the association between strabis-
mus and mental health in diverse populations, leaving gaps
in our understanding of the effect of strabismus across socio-
demographic backgrounds. In this study, we used data from
the National Institutes of Health’s All of Us Research Program
(AoURP)—a large and diverse cohort of US adults—to investi-
gate the association between strabismus and mental health.
Methods
This cross-sectional study used deidentified data from the
AoURP (an ongoing program launched in 2015), adhered to the
Declaration of Helsinki,3 and followed the Strengthening the
Reporting of Observational Studies in Epidemiology (STROBE)
reporting guideline. Secondary analysis of deidentified data
from the AoURP was considered nonhuman participants
research by the Boston Children’s Hospital institutional review
board, which waived approval of the study.
We included all adults (aged ≥18 years) in the AoURP with
a Systemized Nomenclature of Medicine (SNOMED) code for
strabismus and a 1:1 propensity score–matched control group
using age, gender, race and ethnicity, income, educational level,
and health insurance (eTable 1 in Supplement 1). Race and eth-
nicity were self-reported. The racial and ethnic categories are
derived from the survey questionnaire. The racial and ethnic
variables were assessed because this study aims to describe
differences in the association between strabismus and men-
tal health diagnoses across sociodemographic factors. We in-
cluded all adults with a diagnosis of strabismus, regardless of
prior treatments. The outcomes included mental health diag-
noses, categorized into anxiety, depression, substance use and
addiction, bipolar disorder, and schizophrenia spectrum dis-
order (eTable 2 in Supplement 1). Statistical analysis was con-
ducted from September 12, 2023, to January 29, 2024. Logis-
tic regression was used to identify factors associated with
mental health diagnoses. Analyses were conducted using R,
version 4.2.2 (R Project for Statistical Computing) and Py-
thon, version 3.7.12 (Python Software Foundation). All P val-
ues were 2-sided, with P < .05 considered significant, and no
adjustments were made for multiple analyses.
Results
This study included all 3646 AoURP participants with strabis-
mus (median age, 67 years [IQR, 53-76 years]; 2017 women
[55%]) and 3646 propensity score–matched controls (median
age, 67 years [IQR, 53-76 years]; 2017 women [55%]) (Table 1).
Compared with individuals without strabismus, individuals
with strabismus had higher prevalences of anxiety (1153
[32%] vs 519 [14%]; difference, 17%; 95% CI, 15%-19%;
P < .001), depression (1189 [33%] vs 514 [14%]; difference,
19%; 95% CI, 17%-20%; P < .001), substance use and addic-
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Mental Health and Strabismus in the US
Key Points
Question What is the association between strabismus and mental
health conditions in a diverse cohort of US adults?
Findings In this cross-sectional study using data from the National
Institutes of Health’s All of Us Research Program, adults with
strabismus were 2 to 3 times more likely to have a mental health
condition compared with demographically similar adults without
strabismus.
Meaning This study suggests that mental health conditions are
prevalent among adults with strabismus across sociodemographic
backgrounds; efforts are needed to improve mental health
outcomes in this vulnerable population.
tion (116 [3%] vs 51 [1%]; difference, 2%; 95% CI, 1%-3%;
P < .001), bipolar disorder (253 [7%] vs 101 [3%]; difference,
4%; 95% CI, 3%-5%; P < .001), and schizophrenia spectrum
disorder (103 [3%] vs 36 [1%]; difference, 2%; 95% CI, 1%-3%;
P < .001) (Table 2).
Among adults with strabismus, higher odds of mental
health conditions were associated with younger age (odds ra-
tio [OR], 1.11 per 10-year decrease; 95% CI, 1.06-1.16 per 10-
year decrease), female gender (OR, 1.62; 95% CI, 1.41-1.85),
Black or African American race and ethnicity (OR, 1.22; 95%
CI, 1.01-1.48), low income (OR, 3.06; 95% CI, 2.56-3.67), and
high school education or less (OR, 1.58; 95% CI, 1.34-1.85)
(Table 1). Similar associations were identified for gender, in-
come, and educational level in the control group, but with
smaller magnitudes of association. After adjustment for so-
ciodemographic factors using propensity scores, adults with
strabismus had higher odds of anxiety (OR, 2.79; 95% CI, 2.48-
3.13), depression (OR, 2.95; 95% CI, 2.63-3.31), substance use
and addiction (OR, 2.32; 95% CI, 1.66-3.23), bipolar disorder
(OR, 2.62; 95% CI, 2.07-3.31), and schizophrenia spectrum
disorder (OR, 2.92; 95% CI, 1.99-4.27) compared with adults
without strabismus (Table 2).
Discussion
In a diverse nationwide cohort, adults with strabismus were
approximately 2 to 3 times more likely to have mental health
conditions, including anxiety and depression, compared with
adults without strabismus. Our findings are consistent with
existing literature describing an increased prevalence of men-
tal health conditions among individuals with strabismus. Pre-
vious studies have found strabismus to be associated with
anxiety, depression, social phobia, and decreased quality of
life among adults.4-6 Large population-based studies from a
predominantly non-Hispanic White population in Olmstead
County, Minnesota, found that children and adolescents with
strabismus were more likely than age- and sex-matched con-
trols to develop mental health conditions by the second and
third decades of life.7-9 An insurance claim–based study of the
US pediatric population found that children with strabismus
were twice as likely to develop anxiety disorders and were at
increased risk of schizophrenia, bipolar, and depressive
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 Mental Health and Strabismus in the US Brief Report Research

Table 1. Sociodemographic Characteristics of Propensity Score–Matched Study Cohort

and Odds of Mental Health Diagnosis
Demographics of the propensity Association of sociodemographic factors with
score–matched cohorts mental health conditions, OR (95% CI)a
Strabismus Control
Characteristic (n = 3646) (n = 3646) Strabismus Control
Age, median (IQR), yb 67 (53-76) 67 (53-76) 1.11 (1.06-1.16) 1.00 (0.95-1.05)
Race and ethnicity
Asian or otherc 158 (4) 155 (4) 0.75 (0.54-1.03) 0.73 (0.47-1.09)
Black or African 529 (15) 531 (15) 1.22 (1.01-1.48) 0.93 (0.74-1.17)
American
Hispanic or Latino 449 (12) 454 (12) 0.95 (0.77-1.16) 1.05 (0.83-1.33)
Non-Hispanic or 2355 (65) 2359 (65) 1 [Reference] 1 [Reference]
Latino White
Unknown 155 (4) 147 (4) 0.97 (0.70-1.35) 0.71 (0.45-1.08)
Gender
Man 1526 (42) 1527 (42) 1 [Reference] 1 [Reference]
Woman 2017 (55) 2017 (55) 1.62 (1.41-1.85) 1.17 (1.00-1.38)
Other or unknownd 103 (3) 102 (3) 1.58 (1.06-2.37) 0.85 (0.49-1.38)
Income, $
Abbreviation: OR, odds ratio.
>100 000 831 (23) 841 (23) 1 [Reference] 1 [Reference] a
Odds ratios are derived from logistic
50 000-100 000 715 (20) 704 (19) 1.68 (1.37-2.07) 1.34 (1.04-1.73) regression models. Mental health
<50 000 1359 (37) 1364 (37) 3.06 (2.56-3.67) 1.91 (1.55-2.38) conditions include anxiety,
depression, substance use and
Unknown 741 (20) 737 (20) 1.70 (1.39-2.09) 1.26 (0.98-1.62) addiction, bipolar disorder, and
Health insurance schizophrenia spectrum disorder.
b
Yes 3443 (94) 3458 (95) 1 [Reference] 1 [Reference] Odds ratios for age represent a
10-year decrease.
No 81 (2) 74 (2) 1.39 (0.89-2.17) 0.58 (0.29-1.06) c
Other race and ethnicity includes
Unknown 122 (3) 114 (3) 1.54 (1.07-2.24) 0.62 (0.36-1.01) American Indian or Alaska Native,
Hawaiian or Other Pacific Islander,
Educational level
Middle Eastern or North African,
College or more 2767 (76) 2771 (76) 1 [Reference] 1 [Reference] and other race and ethnicity.
d
High school or less 761 (21) 767 (21) 1.58 (1.34-1.85) 1.22 (1.01-1.47) Other gender includes nonbinary,
transgender, and other gender
Unknown 118 (3) 108 (3) 1.01 (0.69-1.46) 0.90 (0.55-1.43)
identity.

Table 2. Prevalence of Mental Health Conditions Among Adults With Strabismus

and Propensity Score–Matched Adults Without Strabismus

Prevalence, No. (%)

Strabismus Control
Mental health diagnosis (n = 3646) (n = 3646)b Difference (95% CI), %a Odds ratio (95% CI) a
Standardized mean difference;
Any mental health 1748 (48) 830 (23) 25 (23-27) 3.12 (2.82-3.46) 2-sample test for equality of
conditionc
proportions.
Anxiety disorder 1153 (32) 519 (14) 17 (15-19) 2.79 (2.48-3.13) b
Propensity score matched on age,
Depressive disorder 1189 (33) 514 (14) 19 (17-20) 2.95 (2.63-3.31) gender, race and ethnicity, income,
educational level, and health
Substance use and addictive 116 (3) 51 (1) 2 (1-3) 2.32 (1.66-3.23)
disorders insurance status.
c
Bipolar disorder 253 (7) 101 (3) 4 (3-5) 2.62 (2.07-3.31) Mental health conditions include
anxiety, depression, substance use
Schizophrenia spectrum 103 (3) 36 (1) 2 (1-3) 2.92 (1.99-4.27) and addiction, bipolar disorder, and
disorder
schizophrenia spectrum disorder.

disorders.10 Our investigation supports these studies with evi-
dence of a similar association between strabismus and mental
health in a diverse cohort of adults from across the US.
We used survey data from the AoURP to explore the role
of several social determinants of health—including age, gen-
der, race and ethnicity, income, educational level, and health
insurance—in the association between strabismus and men-
tal health conditions. Adults with strabismus were more likely
to have mental health diagnoses compared with adults who
were propensity score matched on a range of sociodemo-
graphic factors, suggesting that associations between strabis-
mus and mental health exist across socioeconomic strata. Fur-
thermore, our results suggest that strabismus may also modify
the association between sociodemographic characteristics
and mental health diagnoses. Several factors that were asso-
ciated with mental health conditions among individuals with-

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 Research Brief Report Mental Health and Strabismus in the US

out strabismus (gender, income, and educational level) dem-
onstrated greater magnitudes of association among individuals
with strabismus. The potential for strabismus to dispropor-
tionately exacerbate mental health conditions in historically
marginalized and socioeconomically disadvantaged popula-
tions deserves further investigation.
Given the hereditary nature of some mental health condi-
tions, there may be underlying genetic factors that also pre-
dispose individuals to strabismus. Unfortunately, the genetics
of strabismus, particularly nonsyndromic strabismus, remain
poorly understood. Family and twin studies support a heri-
table component to strabismus, but the contributing genes
remain elusive.11 To date, only 2 loci have been identified
through genome-wide association studies: a functional
single-nucleotide variation in an intron of WRB (also known
as GET1; OMIM 602915) on chromosome 21,12 first identified
in nonaccommodative esotropia and replicated in all forms of
strabismus and divergent strabismus, and the NPLOC4 (OMIM
606590)–TSPAN10 (Genbank 83882)–PDE6G (OMIM 180073)
gene cluster,13 first reported in self-reported strabismus and
replicated in all forms of strabismus, convergent strabismus,
and divergent strabismus. In addition, 3 genetic duplications
have been associated with esotropia and exotropia.14,15 Fur-
ther investigation into the genetics of strabismus subtypes is
needed to understand whether there is overlap with the
genetics of mental health conditions.
Limitations
This investigation has some limitations, including the use of
diagnostic codes to identify both strabismus and mental health
conditions, which were not recorded for research purposes and
are susceptible to coding errors. There are many barriers to re-
ceiving a formal diagnosis of a mental health condition, in-
cluding but not limited to inadequate screening and referral,
cost of care, and stigma.16 Limited health care access may re-
sult in an underestimation of the prevalence of mental health
conditions. In addition, several sociodemographic sub-
groups, such as young adults and individuals identifying as
Black or African American race and ethnicity, have relatively
small sample sizes and wide confidence intervals. It is pos-
sible that some observed associations may be due to chance
or other unmeasured confounding factors. Disability, such as
visual impairment, systemic conditions, and comorbidities as-
sociated with strabismus, may confound the observed asso-
ciations. Other clinical factors, such as the onset, magnitude,
type of strabismus, and history of corrective surgery, may
modify the association of strabismus with mental health but
have incomplete data within the AoURP database.
Conclusions
This cross-sectional study found that, in a diverse and nation-
wide cohort, adults with strabismus were more likely to have
diagnoses of mental health conditions compared with adults
without strabismus. Previous studies among adults with stra-
bismus have found that corrective surgery improved depres-
sion and anxiety questionnaire scores.4 Further investiga-
tion into the risk factors for poor mental health among adults
with strabismus across sociodemographic backgrounds may
offer novel opportunities for interventions to improve men-
tal well-being in this population. Clinicians caring for pa-
tients with strabismus should be aware of the prevalence of
mental health conditions—especially among individuals from
historically marginalized and socioeconomically disadvan-
taged backgrounds.

ARTICLE INFORMATION
Accepted for Publication: February 3, 2024.
Published Online: April 4, 2024.
doi:10.1001/jamaophthalmol.2024.0540
Author Contributions: Ms Jin had full access to all
of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the
data analysis.
Concept and design: Jin, Whitman, Oke.
Acquisition, analysis, or interpretation of data: Jin,
Aboobakar, Oke.
Drafting of the manuscript: Jin, Oke.
Critical review of the manuscript for important
intellectual content: All authors.
Statistical analysis: Jin, Aboobakar.
Obtained funding: Oke.
Supervision: Oke.
Conflict of Interest Disclosures: Dr Whitman
reported receiving grants from the National Eye
Institute and the Massachusetts Lions Foundation
outside the submitted work. Dr Oke reported
receiving grants from Research to Prevent
Blindness, the Knights Templar Eye Foundation,
and the Boston Children’s Hospital Office for
Faculty Development outside the submitted work.
No other disclosures were reported.
Funding/Support: This study was supported by
grant K12TR004381 from the National Center for
Advancing Translational Sciences (Dr Oke),
Children’s Hospital Ophthalmology Foundation (Dr
Oke), grant R01EY032539 from the National Eye
Institute (Dr Whitman), and Boston Children’s
Hospital Translational Research Program
(Dr Whitman).
Role of the Funder/Sponsor: The funding sources
had no role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
Data Sharing Statement: See Supplement 2.
Additional Contributions: The All of Us Research
Program is supported by the National Institutes of
Health. We thank the participants of the All of Us
Research Program, who make this work possible.
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