Retinal Microvasculature in Schizophrenia

Abstract

Purpose: Schizophrenia is associated with alterations in neural structure and function of the retina that are similar to changes seen in the retina and brain in multiple neurodegenerative disorders. Preliminary evidence suggests that retinal microvasculature may also be compromised in schizophrenia. The goal of this study was to determine, using optical coherence tomography angiography (OCTA), whether 1) schizophrenia is associated with alterations in retinal microvasculature density; and 2) microvasculature reductions are associated with retinal neural layer thinning and performance on a measure of verbal IQ.

Patients and methods: Twenty-eight outpatients with schizophrenia or schizoaffective disorder and 37 psychiatrically healthy control subjects completed OCT and OCTA exams, and the Wechsler Test of Adult Reading.

Results: Schizophrenia patients were characterized by retinal microvasculature density reductions, and enlarged foveal avascular zones, in both eyes. These microvascular abnormalities were generally associated with thinning of retinal neural (macular and peripapillary nerve fiber layer) tissue (but the data were stronger for the left than the right eye) and lower scores on a proxy measure of verbal IQ. First- and later-episode patients did not differ significantly on OCTA findings.

Conclusion: The retinal microvasculature impairments seen in schizophrenia appear to be a biomarker of overall brain health, as is the case for multiple neurological conditions. Additional research is needed, however, to clarify contributions of social disadvantage and medical comorbidities to the findings.

Keywords: OCT angiography; OCTA; arteriole; retina; schizophrenia; venule.

Figure 1

OCTA images of superficial retinal layer vasculature in a psychiatrically healthy control subject (top left) that was age-matched to a later-episode schizophrenia patient (bottom left). Reduced microvasculature density is clearly visible in the lower image (see also Figures 2–4 for additional information). The foveal avascular zone is highlighted with a red border. This region was larger in the schizophrenia sample (see Table 3). The same subsection of each image, bounded by a yellow square, is enlarged and shown to the right of each primary image. Microvasculature reduction is more easily visible in these enlargements, despite the lowered resolution.

Figure 2

Perfusion density traces of the images shown in Figure 1. These images are binarized, so that regions that exceed a standard brightness threshold are rendered in white, while all other regions are rendered in black. These images depict the total area of the image containing blood vessels. The smaller images to the right are magnified views of the regions bordered by yellow squares. These images offer an additional perspective on retinal microvasculature reduction observed in schizophrenia.

Figure 3

Box plots of perfusion density values for the left eye (left panel) and right eye (right panel), by group. Density is expressed the proportion of total area in the 3×3 mm² image in which blood vessels are visible. Asterisks signify data points between 1–3 interquartile ranges from the lower hinge (25th percentile) of the boxplot. The main effect of group was significant in both cases. See text for statistical test results.

Figure 4

Box plots of vessel density values for the left eye (left panel) and right eye (right panel), by group. Density is expressed as total length of all vessels in the 3×3 mm² image, in mm⁻¹. Asterisks signify data points between 1–3 interquartile ranges from the lower hinge (25th percentile) of the boxplot. The main effect of group was significant in both cases. See text for statistical test results.

Figure 5

Scatterplots of relationships between left eye (OS) perfusion and vessel density values as predictors of left eye macula central subfield (CSF) thickness and cube volume, for the entire sample. Each panel shows all data points along with the best-fitting least-squares regression line (in red, labeled as “estimate”), upper and lower 95% confidence limits for a single mean response (inner, blue lines), and prediction limits for new observations (outer, cyan lines). The Spearman rho correlation coefficient and accompanying p-value, expressing the strength of the relationship between variables, is shown in the lower right portion of each panel. Panels display relationships between: (A) perfusion density and CSF thickness; (B) vessel density and CSF thickness; (C) perfusion density and cube volume; and (D) vessel density and cube volume. The same overall pattern of positive relationships existed in the right eye data, but relationships between variables were weaker than for the left eye in all cases. The relationships between variables were similar for patients and control subjects when considered as separate groups.