Clinical Context

Among older adults, satisfaction and good health require good visual functioning. With aging, vision-related problems have major public health implications by worsening activities of daily living (ADL), morbidity, and mortality.

Visual impairment contributes to depression, another major societal burden projected to be the primary cause of disease burden worldwide by 2030. Mechanisms underlying the relationship between depression and visual loss are unclear but may include shared risk factors or difficulties in ADL because of visual impairment.

Study Synopsis and Perspective

Poor visual acuity, defined as difficulty discerning letters or numbers at a given distance, is associated with depression in middle-aged and older individuals, new research suggests.

After multiple adjustments, analysis of data from more than 114,000 participants in the UK Biobank Study showed that visual impairment was linked to a 19% higher risk for depression.

In addition, imaging results showed a significant link between deteriorating brain structures and depression in those with poor visual acuity.

"Our findings highlight the value of visual health in association with mental health," Xiayin Zhang, PhD, Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital, Guangzhou, China, and colleagues write.

"Screening of vision at an early stage should be embedded in the middle-aged and older population to stratify the vulnerable population at risk for depression," the investigators add.

The findings were published online October 6 in JAMA Network Open.

The analysis included 114,583 participants (54.5% women; mean age, 56.8 years) from the UK Biobank who completed standardized questionnaires and underwent ocular examinations.

To test distance visual acuity, all participants were asked to read letters on lines from the top to the bottom of a chart while wearing prescribed optical correction. Visual impairment was defined as visual acuity worse than 0.3 logarithm of the minimum angle of resolution (LogMAR) units.

Depressive symptoms were self-reported using the 2-item Patient Health Questionnaire (PHQ-2), in which a score of 3 or more indicates depression. As well, a medical practitioner conducted an assessment of depression at baseline.

Among the participants, 87.2% had no visual impairment or depression and acted as the healthy control group. In addition, 3.2% showed visual impairment, 10.0% reported a diagnosis of depression, and 0.4% had both.

Researchers adjusted for age, sex, race, ethnicity, education, smoking, alcohol consumption, physical activity, family history of severe depression, obesity, hypertension, diabetes, hyperlipidemia, and deprivation on the Townsend index.

Among those with visual impairment, 12.4% had depression compared with 9.9% without visual impairment.

After adjusting for potential confounders, visual impairment was associated with a 19% higher risk for depression (odds ratio [OR], 1.19; 95% CI, 1.05-1.34; P=.003). In addition, 1-line worse visual acuity was associated with 5% higher odds of depression (OR, 1.05; 95% CI, 1.04-1.07; P<.001).

The association between visual acuity and depression was found in both younger (39-58 years) and older (59-72 years) groups, as well as in both men and women.

The researchers also explored the association between depressive symptoms and brain structure, using MRI scans from a subset of 7844 individuals (51% women; 2% with visual impairment).

Results showed linear associations between PHQ-2 scores and the left volume of gray matter in the supracalcarine cortex (coefficient, 7.61; 95% CI, 3.90-11.31; adjusted P=.006).

The investigators note that the supracalcarine cortex is spatially connected to the primary visual cortex,suggesting that the visual cortex may be involved in the pathogenesis of depression.

PHQ-2 scores were also associated with mean isotropic volume fraction (ISOVF) in the right fornix (cres) and/or stria terminalis (coefficient, 0.003; 95% CI, 0.001-0.004; adjusted P=.01).

The links "could be moderated by visual acuity, whereby increased PHQ score was associated with higher ISOVF levels only among those with poorer visual acuity (P = .02 for interaction)," the investigators report.

These results "suggest that poorer visual acuity was associated with greater depressive symptoms and may have contributed to the related deterioration of the fornix and stria terminalis," they add.

They note that previous studies have supported the hypothesis that the fornix and stria terminalis are involved in the pathophysiology of other brain-related conditions, including schizophrenia, bipolar disorder, and autism spectrum disorder.

However, the investigators did not have information on how long the participants had experienced visual impairment, so they could not investigate whether results were affected by time. Additional study limitations cited were that depression may affect vision and that a large proportion of the participants (89.3%) were White.

Commenting for Medscape Medical News, Ipsit V. Vahia, MD, associate chief of geriatric psychiatry at McLean Hospital and assistant professor of psychiatry at Harvard Medical School, Boston, Massachusetts, said that the study "adds nuance to our understanding" of the well-established relationship between vision deficits and depression.

"It indicates that even mild visual deficits may be associated with depression," said Dr Vahia, who was not involved with the research.

The investigators validated this association by showing that visual acuity was also associated with neuroimaging markers of depression, he added.

Although the study was not designed to demonstrate causal relationships between mood and vision and its findings do not confirm that correcting visual acuity deficits will resolve depressive symptoms, "the large study sample and high quality of data should give clinicians confidence in the study's findings," Dr Vahia said.

"Correcting visual acuity deficits can be considered standard care for older adults worldwide, and this study suggests that providing this standard care could also benefit mental health," he concluded.

The study was supported by the National Natural Science Foundation of China; the China Postdoctoral Science Foundation; the Outstanding Young Talent Trainee Program of Guangdong Provincial People's Hospital; the Guangdong Provincial People's Hospital Scientific Research Funds for Leading Medical Talents and Distinguished Young Scholars in Guangdong Province; the Talent Introduction Fund of Guangdong Provincial People's Hospital; the Science and Technology Program of Guangzhou, China; the Project of Special Research on Cardiovascular Diseases; the Research Foundation of Medical Science and Technology of Guangdong Province; the University of Melbourne at Research Accelerator Program; and the CERA (Centre for Eye Research Australia) Foundation and Victorian State Government for the Centre for Eye Research Australia. The investigators and Dr Vahia have reported no relevant financial relationships.

JAMA Netw Open. Published online October 6, 2022.^[1]

Study Highlights

• In UK Biobank, 114,583 volunteers were included at baseline between March to June 2006 and July 2010 and underwent assessment of habitual distance visual acuity, depression, depressive symptoms, and imaging-derived phenotype from T1-weighted and diffusion MRI.
• Mean age was 56.8±8.1 (range, 39-72) years; 54.5% were women, 87.2% had no visual impairment or depression, 3.2% had visual impairment, 10.0% had depression, and 0.4% had both.
• 12.4% of those with and 9.9% of those without visual impairment had depression.
• Visual impairment was associated with 19% higher depression risk (OR, 1.19; 95% CI, 1.05-1.34; P=.003), after adjustment for age, sex, race and ethnicity, Townsend index, education, smoking, alcohol intake, obesity, physical activity, history of hypertension, diabetes, hyperlipidemia, and family history of depression.
• One-line worse visual acuity (0.1 LogMAR increase) was associated with 5% higher adjusted odds of depression (OR, 1.05; 95% CI, 1.04-1.07; P<.001).

Figure. Association Between Visual Acuity and Depression

• Visual acuity was associated with depression in younger (age 39-58 years) and older (age 59-72 years) groups and in men and women.
• Among 7844 participants (51% women; 2% with visual impairment) eligible for MRI analysis, PHQ score was linearly associated with gray matter volume in left supracalcarine cortex (coefficient, 7.61; 95% CI, 3.90-11.31; adjusted P=.006) and mean ISOVF in right fornix (cres) and/or stria terminalis (coefficient, 0.003; 95% CI, 0.001-0.004; P=.01) after correction for multiple comparisons.
• There were dose-response-type gradients between PHQ score and ISOVF in the fornix (cres) and/or stria terminalis.
• Visual acuity moderated these associations, with increased PHQ score associated with higher ISOVF levels only among those with poorer visual acuity (P=.02 for interaction).
• The investigators concluded that poorer visual acuity across the full spectrum was associated with depressive symptoms and that the diffusion characteristic of ISOVF in the fornix (cres) and/or stria terminalis is associated with depressive symptoms in participants with poorer visual acuity.
• Significantly higher ISOVF in the fornix (cres) and/or stria terminalis suggests increased extracellular component of the free-water compartment.
• As the findings suggest associations of visual health with depressive symptoms and depression-related altered brain neurobiology, clinicians should consider these outcomes when performing routine mental health screening.
• Poorer visual acuity across the full spectrum is a potentially modifiable risk factor for depression, consistent with epidemiological literature.
• Visual acuity correction could potentially prevent underrecognized or preclinical depression, mandating regular visual health screening for middle-aged and older patients and coordinating with mental health services to provide holistic care.
• As the supracalcarine cortex is spatially connected to the primary visual cortex, the visual cortex may be involved in depression pathogenesis.
• Poorer visual acuity was associated with greater depressive symptoms and may have contributed to fornix and stria terminalis deterioration.
• Previous research suggests fornix and stria terminalis involvement in the pathophysiology of schizophrenia, bipolar disorder, autism spectrum disorder, and other brain-related conditions.
• Study limitations include lack of data on visual impairment duration, precluding temporal inferences, and lack of generalizability to non-White patients.
• Future research should examine causal relationships among visual health, depression, and brain changes.

Clinical Implications

• Poorer visual acuity was associated with depressive symptoms and brain structure changes.
• Poorer visual acuity across the full spectrum is a potentially modifiable risk factor for depression.

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