Association Between Retinal Features From Multimodal Imaging and Schizophrenia
Authors: Wagner Siegfried K. , Cortina-Borja Mario , Silverstein Steven M. , Zhou Yukun , Romero-Bascones David , Struyven Robbert R. , Trucco Emanuele , Mookiah Muthu R. K. , MacGillivray Tom , Hogg Stephen , Liu Timing , Williamson Dominic J. , Pontikos Nikolas , Patel Praveen J. , Balaskas Konstantinos , Alexander Daniel C. , Stuart Kelsey V. , Khawaja Anthony P. , Denniston Alastair K. , Rahi Jugnoo S. , Petzold Axel , Keane Pearse A. 
Published: March 2023

Importance

The potential association of schizophrenia with distinct retinal changes is of clinical interest but has been challenging to investigate because of a lack of sufficiently large and detailed cohorts.

Objective

To investigate the association between retinal biomarkers from multimodal imaging (oculomics) and schizophrenia in a large real-world population.

Design, Setting, and Participants

This cross-sectional analysis used data from a retrospective cohort of 154 830 patients 40 years and older from the AlzEye study, which linked ophthalmic data with hospital admission data across England. Patients attended Moorfields Eye Hospital, a secondary care ophthalmic hospital with a principal central site, 4 district hubs, and 5 satellite clinics in and around London, United Kingdom, and had retinal imaging during the study period (January 2008 and April 2018). Data were analyzed from January 2022 to July 2022.

Main Outcomes and Measures

Retinovascular and optic nerve indices were computed from color fundus photography. Macular retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer (mGC-IPL) thicknesses were extracted from optical coherence tomography. Linear mixed-effects models were used to examine the association between schizophrenia and retinal biomarkers.

Results

A total of 485 individuals (747 eyes) with schizophrenia (mean [SD] age, 64.9 years [12.2]; 258 [53.2%] female) and 100 931 individuals (165 400 eyes) without schizophrenia (mean age, 65.9 years [13.7]; 53 253 [52.8%] female) were included after images underwent quality control and potentially confounding conditions were excluded. Individuals with schizophrenia were more likely to have hypertension (407 [83.9%] vs 49 971 [48.0%]) and diabetes (364 [75.1%] vs 28 762 [27.6%]). The schizophrenia group had thinner mGC-IPL (−4.05 μm, 95% CI, −5.40 to −2.69; P = 5.4 × 10−9), which persisted when investigating only patients without diabetes (−3.99 μm; 95% CI, −6.67 to −1.30; P = .004) or just those 55 years and younger (−2.90 μm; 95% CI, −5.55 to −0.24; P = .03). On adjusted analysis, retinal fractal dimension among vascular variables was reduced in individuals with schizophrenia (−0.14 units; 95% CI, −0.22 to −0.05; P = .001), although this was not present when excluding patients with diabetes.

Conclusions and Relevance

In this study, patients with schizophrenia had measurable differences in neural and vascular integrity of the retina. Differences in retinal vasculature were mostly secondary to the higher prevalence of diabetes and hypertension in patients with schizophrenia. The role of retinal features as adjunct outcomes in patients with schizophrenia warrants further investigation.