Association Between Retinal Features From Multimodal Imaging and Schizophrenia

Siegfried K Wagner*, Mario Cortina-Borja, Steven M Silverstein, Yukun Zhou, David Romero-Bascones, Robbert R Struyven, Emanuele Trucco, Muthu R K Mookiah, Tom MacGillivray, Stephen Hogg, Timing Liu, Dominic J Williamson, Nikolas Pontikos, Praveen J Patel, Konstantinos Balaskas, Daniel C Alexander, Kelsey V Stuart, Anthony P Khawaja, Alastair K Denniston, Jugnoo S RahiAxel Petzold, Pearse A Keane

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)478-487
Number of pages10
JournalJAMA Psychiatry
Issue number5
Early online date22 Mar 2023
Publication statusPublished - 1 May 2023

Keywords / Materials (for Non-textual outputs)

  • Humans
  • Female
  • Aged
  • Middle Aged
  • Male
  • Retinal Ganglion Cells
  • Retrospective Studies
  • Cross-Sectional Studies
  • Schizophrenia/diagnostic imaging
  • Retina/diagnostic imaging
  • Hypertension
  • Tomography, Optical Coherence/methods
  • Multimodal Imaging


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