Optical Coherence Tomography in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-analysis.

Background: Inner retinal atrophy has been demonstrated in schizophrenia spectrum disorder (SSD) using optical coherence tomography (OCT). This systematic review and meta-analysis investigated the role of contemporary Fourier domain OCT devices in SSD.

Methods: MEDLINE, PubMed, Scopus, Embase, PsycInfo, PYSNDEX, World Health Organization, and Cochrane databases were searched from inception until May 2022. All peer-reviewed adult SSD case-control studies using Fourier domain OCT were included. Ocular pathologies known to affect retinal OCT scans were excluded. Search, data appraisal, and summary data extraction were independently performed by 2 authors.

Results: The review criteria was met by k = 36 studies, with k = 24 studies (1074 cases, 854 controls) suitable for meta-analysis. The SSD group exhibited a thinner global peripapillary retinal nerve fiber layer (-3.26 μm, 95% CI, -5.07 to -1.45,  = 64%, k = 21), thinner average macular layer (-7.88 μm, 95% CI, -12.73 to -3.04,  = 65%, k = 11), and thinner macular ganglion cell-inner plexiform sublayer (-2.44 μm, 95% CI, -4.13 to -0.76,  = 30%, k = 8) compared with the control group. Retinal nerve fiber layer findings remained significant after exclusion of metabolic disease, low quality, outlier, and influential studies. Studies involving eye examinations to exclude eye disease were associated with greater atrophy in SSD. Except for cardiometabolic disease, most studies did not report clinically significant covariate data known to influence retinal thickness.

Conclusions: Individuals with SSD generally exhibited retinal atrophy, possibly paralleling reduced brain volumes documented in clinical imaging. Prospective longitudinal studies that collect clinical data, including various illness phases, and control for confounders will be necessary to evaluate retinal atrophy as a biomarker in SSD.