Retinal nerve fiber layer and macular thickness in patients with schizophrenia: Influence of recent illness episodes

Abstract

Optical coherence tomography (OCT) has been recently used to investigate neuropsychiatric disorders. We aimed to study retinal OCT measures of patients with schizophrenia with respect to healthy controls, and to evaluate possible differences between recent illness episode (RIE) and non-recent illness episode (NRIE) patients. Thirty schizophrenia patients were classified as RIE (n=10) or NRIE (n=20), and compared with 30 matched controls. Statistical analyses included linear mixed-effects models to study the association between OCT measures and group membership. Multivariate models were used to control for potential confounders. In the adjusted linear mixed-effects regression model, patients had a significantly thinner retinal nerve fiber layer (RNFL) in overall measurements, and in the nasal, superior and inferior quadrants. Macular inner ring thickness and macular volume were also significantly smaller in patients than controls. Compared with controls, in the adjusted model only NRIE (but not RIE) patients had significantly reduced RNFL overall measures, superior RNFL, nasal RNFL, macular volume, and macular inner ring thickness. No significant correlation was found between illness duration and retinal measurements after controlling for age. In conclusion, retinal parameters observed using OCT in schizophrenia patients could be related to clinical status and merit attention as potential state biomarkers of the disorder.

Introduction

Schizophrenia is one of the most severe mental disorders and a serious public health problem. The diagnosis of schizophrenia relies primarily on identifying the characteristic symptoms of the disorder through a clinical interview. Nevertheless, in view of the variety of clinical presentations of schizophrenia among different patients, and the symptom overlap with other disorders (Demirci and Calhoun, 2009), objective markers for diagnosing schizophrenia and related conditions are currently being sought (Zarogianni et al., 2013). The interest of biomarkers in schizophrenia has been emphasized in recent reports (Kasper, 2013), especially those based on neuroimaging methods. Neuroimaging techniques have been extensively studied over the past years, and there is now a considerable number of studies including structural and functional magnetic resonance imaging that aim to develop new diagnostic markers for schizophrenia. Relevant findings of neuroimaging studies in patients with schizophrenia include gray (Glahn et al., 2008) and white (Takayanagi et al., 2013, Bracht et al., 2014) matter abnormalities. Nevertheless, at the present moment it is difficult to draw firm conclusions regarding the precise nature of the underlying neuropathology of the disorder (Fornito et al., 2009). In this context, optical coherence tomography (OCT), a non-invasive imaging technique, provides reproducible, high-resolution cross-sectional imaging of the retinal nerve fiber layer (RNFL) and optic nerve head topography, providing an objective tool to diagnose axonal damage and thus constituting a “window into the brain” (London et al., 2013). A significant reduction in peripapillary RNFL thickness has been reported in patients with various neurological disorders such as multiple sclerosis (Sergott et al., 2007, Thrower, 2007), Alzheimer's disease (Parisi et al., 2001, Berisha et al., 2007, Marziani et al., 2013, Larrosa et al., 2014, Ascaso et al., 2014) or Parkinson's disease (Inzelberg et al., 2004, Hajee et al., 2009, Garcia-Martin et al., 2014, Jimenez et al., 2014), suggesting that this technique may also prove to be useful in other neuropsychiatric disorders.

Together with these neuroimaging findings, the impaired functioning of the visual system and the retinal alterations found in patients with schizophrenia support the use of OCT to investigate this disorder (Meier et al., 2013). In the first study reported in the literature, our group found a decreased RNFL thickness as measured with OCT in patients with schizophrenia (Ascaso et al., 2010). Similar results have been later reported by Lee et al. (2013), who additionally found a relationship between abnormal OCT parameters and illness duration, but not by Chu et al. (2012), who did not find significant differences in retinal parameters between patients in the early stages of illness and controls.

Thus, the goal of our study was to confirm in a larger sample of patients with schizophrenia the findings described in our first report, testing the hypothesis that a significant thinning of peripapillary RNFL and macular thickness would be found in schizophrenia patients when compared with controls. In addition, on the basis of the contradictory findings reported in the literature, we explored the hypothesis that abnormal OCT parameters would be observed in patients with non-recent illness episodes (NRIE) of schizophrenia, but not in patients with a recent illness episode (RIE). Finally, we studied the correlation between abnormal OCT parameters and illness duration.