The retina across the psychiatric spectrum: a systematic review and meta-analysis

The identification of structural retinal layer differences between patients diagnosed with certain psychiatric disorders and healthy controls has provided a potentially promising route to the identification of biomarkers for these disorders. Optical coherence tomography has been used to study whether retinal structural differences exist in schizophrenia spectrum disorders (SSD), bipolar disorder (BPD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and alcohol and opiate use disorders. However, there is considerable variation in the amount of available evidence relating to each disorder and heterogeneity in the results obtained. We conducted the first systematic review and meta-analysis of evidence across all psychiatric disorders for which data was available. The quality of the evidence was graded and key confounding variables were accounted for. Of 381 screened articles, 87 were included. The evidence was of very low to moderate quality. Meta-analyses revealed that compared to healthy controls, the peripapillary retinal nerve fiber layer (pRNFL) was significantly thinner in SSD (SMD = -0.32; p<0.001), BPD (SMD = -0.4; p<0.001), OCD (SMD = -0.26; p=0.041), and ADHD (SMD = -0.48; p=0.033). Macular thickness was only significantly less in SSD (SMD = -0.59; p<0.001). pRNFL quadrant analyses revealed that reduced pRNFL thickness in SSD and BPD was most prominent in the superior and inferior quadrants. Macular subfield analyses indicated that BPD may have region-specific effects on retinal thickness. In conclusion, these findings suggest substantial retinal differences in SSD and BPD, reinforcing their potential as biomarkers in clinical settings.