Retinal Changes in Schizophrenia: A Systematic Review and Meta-analysis Based on Individual Participant Data

Background: Retinal assessment has indicated the presence of neuronal loss in neurodegenerative disorders, but its role in schizophrenia remains unclear. We sought to synthesize the available evidence considering 3 noninvasive modalities: optical coherence tomography, electroretinography, and fundus photography, and examine their diagnostic accuracy based on unpublished individual participant data, when provided by the primary study authors. Methods: We searched MEDLINE, SCOPUS, clinicaltrials.gov, PSYNDEX, Cochrane Controlled Register of Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and Google Scholar, up to October 30, 2018. Authors were contacted and invited to share anonymized participant-level data. Aggregate data were pooled using random effects models. Diagnostic accuracy meta-analysis was based on multiple cutoffs logistic generalized linear mixed modeling. This study was registered with PROSPERO, number CRD42018109344. Results: Pooled mean differences of peripapillary retinal nerve fiber layer thickness in micrometer between 694 eyes of 432 schizophrenia patients and 609 eyes of 358 controls, from 11 case-control studies, with corresponding 95% confidence intervals (CIs) by quadrant were the following: -4.55, 95% CI: -8.28, -0.82 (superior); -6.25, 95% CI: -9.46, -3.04 (inferior); -3.18, 95% CI: -5.04, -1.31 (nasal); and -2.7, 95% CI: -4.35, -1.04 (temporal). Diagnostic accuracy, based on 4 studies, was fair to poor, unaffected by age and sex; macular area measurements performed slightly better. Conclusion: The notion of structural and functional changes in retinal integrity of patients with schizophrenia is supported with current evidence, but diagnostic accuracy is limited. The potential prognostic, theranostic, and preventive role of retinal evaluation remains to be examined.