Systematic review and meta-analysis of retinal microvascular caliber in bipolar disorder, major depressive disorder, and schizophrenia

Background: Individuals with a severe mental illness (SMI), such as bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ), have increased rates of cardiovascular and cerebrovascular disease. Interestingly, it has been reported that retinal microvessels, a proxy cerebrovascular measure, non-invasively assessed via retinal imaging, predict future cardiovascular disease, with some studies also showing anomalous retinal microvascular caliber in SMI. Therefore, this review and meta-analysis evaluated whether retinal microvascular caliber differs between individuals with SMI vs controls and summarized current findings.

Methods: A systematic literature search for retinal microvascular caliber and SMI was conducted in Embase and MEDLINE. Studies needed to be published in English before 2022 December 1st and examine retinal microvascular caliber in individuals diagnosed with a SMI. Finally, a meta-analysis of arteriolar and venular caliber in SMI case-controlled studies was also conducted.

Results: The search yielded 65 unique articles, 11 were included in the review and 6 in the meta-analysis. The meta-analysis found that the SMI group had significantly wider venules than controls (SMD = 0.53; 95 % CI = 0.24, 0.81; p = 0.0004) but not arterioles (SMD = 0.07; 95 % CI = -0.29, 0.44; p = 0.70). Additionally, the systematic review found that poorer retinal microvascular health is associated with greater illness severity.

Limitations: Large heterogeneity of findings and small sample size.

Conclusion: This systematic review and meta-analysis found that SMI, specifically SZ, is associated with wider retinal venules. Retinal imaging, a fast, cost-effective, and non-invasive assay of cerebrovascular health, may provide insight into the pathophysiological processes of SMI. However, future longitudinal studies investigating these findings are warranted.