Neuroretinal Alterations in Schizophrenia and Bipolar Disorder: An Updated Meta-analysis

Abstract

Schizophrenia (SZ) and bipolar disorder (BD) are characterized by major symptomatic, cognitive, and neuroanatomical changes. Recent studies have used optical coherence tomography (OCT) to investigate retinal changes in SZ and BD, but their unique and shared changes require further evaluation. Articles were identified using PubMed and Google Scholar. 39 studies met the inclusion criteria. Diagnostic groups were proband (SZ/BD combined), SZ, BD, and healthy control (HC) eyes. Meta-analyses utilized fixed and random effects models when appropriate, and publication bias was corrected using trim-and-fill analysis ("meta" package in R). Results are reported as standardized mean differences with 95% CIs. Data from 3145 patient eyes (1956 SZ, 1189 BD) and 3135 HC eyes were included. Studies identified thinning of the peripapillary retinal nerve fiber layer (pRNFL, overall and in 2 subregions), m-Retina (overall and all subregions), mGCL-IPL, mIPL, and mRPE in SZ patients. BD showed thinning of the pRNFL (overall and in each subregion), pGCC, and macular Retina (in 5 subregions), but no changes in thickness or volume for the total retina. Neither SZ nor BD patients demonstrated significant changes in the fovea, mRNFL, mGCL, mGCC, mINL, mOPL, mONL, or choroid thicknesses. Moderating effects of age, illness duration, and smoking on retinal structures were identified. This meta-analysis builds upon previous literature in this field by incorporating recent OCT studies and examining both peripapillary and macular retinal regions with respect to psychotic disorders. Overall, this meta-analysis demonstrated both peripapillary and macular structural retinal abnormalities in people with SZ or BD compared with HCs.

Keywords: bipolar disorder; macula; peripapillary; retinal imaging; schizophrenia.

Fig. 1.

Diagram of study selection process. Diagram demonstrating the number of articles identified and screened, as well as those that were eligible and then those that were included in the meta-analysis.

Fig. 2.

Summary bar plots of retinal differences in the peripapillary and macular area. Peripapillary measures for Total pRetina, pRNFL, pGCL, pGCL-IPL, pGCC, and pIPL. Note: GCC, ganglion cell complex; GCL, ganglion cell layer; GCL-IPL, ganglion cell layer-inner plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; p, peripapillary; RNFL, retinal nerve fiber layer. *P < .05.

Fig. 3.

Summary bar plots of retinal differences in the macular area. (A) m-Total Retina, fovea, inner and outer m-Total Retina superior, inferior, nasal, and temporal subregion thicknesses, and macular volume (MV); (B) mRNFL, mGCL, mGCL-IPL, mGCC, mIPL, mINL, mOPL, mONL, mRPE, mChoroid thicknesses, and GCL and IPL volumes. Note: GCC, ganglion cell complex; GCL, ganglion cell layer; GCL-IPL, ganglion cell layer-inner plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; m, macular; ONL, outer nuclear layer; OPL, outer plexiform layer; RNFL, retinal nerve fiber layer; RPE, retinal pigmented epithelium. *P < .05.