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Retinal layers and associated clinical factors in schizophrenia spectrum disorders: a systematic review and meta-analysis

A Correction to this article was published on 09 February 2023

A Correction to this article was published on 27 May 2022

This article has been updated

Abstract

Introduction

The retina shares structural and functional similarities with the brain. Furthermore, structural changes in the retina have been observed in patients with schizophrenia spectrum disorders (SSDs). This systematic review and meta-analysis investigated retinal abnormalities and their association with clinical factors for SSD.

Methods

Studies related to retinal layers in SSD patients were retrieved from PubMed, Scopus, Web of Science, Cochrane Controlled Register of Trials, International Clinical Trials Registry Platform, and PSYNDEX databases from inception to March 31, 2021. We screened and assessed the eligibility of the identified studies. EZR ver.1.54 and the metafor package in R were used for the meta-analysis and a random-effects or fixed-effects model was used to report standardized mean differences (SMDs).

Results

Twenty-three studies (2079 eyes of patients and 1571 eyes of controls) were included in the systematic review and meta-analysis. The average peripapillary retinal nerve fiber layer (pRNFL) thickness, average macular thickness (MT), and macular ganglion cell layer-inner plexiform layer (GCL-IPL) thickness were significantly lower in patients than in controls (n = 14, 6, and 3, respectively; SMD = −0.33, −0.49, and −0.43, respectively). Patients also had significantly reduced macular volume (MV) compared to controls (n = 7; SMD = −0.53). The optic cup volume (OCV) was significantly larger in patients than in controls (n = 3; SMD = 0.28). The meta-regression analysis indicated an association between several clinical factors, such as duration of illness and the effect size of the pRNFL, macular GCL-IPL, MT, and MV.

Conclusion

Thinning of the pRNFL, macular GCL-IPL, MT, and MV and enlargement of the OCV in SSD were observed. Retinal abnormalities may be applicable as state/trait markers in SSDs. The accumulated evidence was mainly cross-sectional and requires verification by longitudinal studies to characterize the relationship between OCT findings and clinical factors.

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Fig. 1: PRISMA flow diagram for the meta-analysis and systematic review.
Fig. 2: Meta-analysis of pRNFL thickness, macular volume, average macular thickness, macular GCL-IPL thickness, and optic cup volume.
Fig. 3: Meta-analysis of the inferior, nasal, superior, and temporal quadrants of the pRNFL thickness.
Fig. 4: Meta-analysis of the eight segments in the macular thickness, and of the central foveal thickness and cup-to-disc area ratio.

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Data availability

The data that support the findings of this study are available from the corresponding author, HK, upon reasonable request.

Change history

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Acknowledgements

This work was partially supported by the Tohoku University Advanced Research Center for Innovations in Next-Generation Medicine. We would like to thank Dr Francisco J. Ascaso, Thomas Krege, and Schönfeldt-Lecuona for their comments on our inquiry. We would like to thank Editage (www.editage.com) for English language editing.

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HK, GO, and HT made substantial contributions to the conception and design of the study. HK and GO collected the data needed for a systematic review and meta-analysis. HK performed statistical analyses based on data collected. HK, OG, and HT contributed to the interpretation of the data and results of the statistical analysis. HK was involved in drafting the manuscript. TY, TN, YK, TO, SF, SJ, NK, and HT critically revised the manuscript for important intellectual content. All authors read and approved the final version of the manuscript and agreed on the order in which their names were listed in the manuscript.

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Correspondence to Hiroshi Komatsu.

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The original online version of this article was revised: Incorrect search terms listed in the methods section of the published article: retinal OR retina OR optical coherence tomography AND schizophrenia OR psychosis.

The original online version of this article was revised: We found an error in the formula for adding the standard deviations of the retinal layer thickness of the left and right eyes in the methods section. The formula in the methods section is incorrect. The results of the present study do not change because the correct formula is used in the calculation.

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Komatsu, H., Onoguchi, G., Jerotic, S. et al. Retinal layers and associated clinical factors in schizophrenia spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 27, 3592–3616 (2022). https://doi.org/10.1038/s41380-022-01591-x

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