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. 2023 May 1;80(5):478-487.
doi: 10.1001/jamapsychiatry.2023.0171.

Association Between Retinal Features From Multimodal Imaging and Schizophrenia

Siegfried K Wagner  1   2   3 , Mario Cortina-Borja  4 , Steven M Silverstein  5   6   7   8 , Yukun Zhou  1   2   9 , David Romero-Bascones  3   10 , Robbert R Struyven  1   2   3   9 , Emanuele Trucco  11 , Muthu R K Mookiah  11 , Tom MacGillivray  12 , Stephen Hogg  11 , Timing Liu  3 , Dominic J Williamson  1   2   3   9 , Nikolas Pontikos  1   2   3 , Praveen J Patel  1   2   3 , Konstantinos Balaskas  1   2   3 , Daniel C Alexander  9 , Kelsey V Stuart  1   2   3 , Anthony P Khawaja  1   2   3 , Alastair K Denniston  13   14   15 , Jugnoo S Rahi  1   2   4   16   17   18 , Axel Petzold  1   3   19 , Pearse A Keane  1   2   3
Affiliations

Association Between Retinal Features From Multimodal Imaging and Schizophrenia

Siegfried K Wagner et al. JAMA Psychiatry. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Wagner reported having developed (with others) the AutoMorph retinal analysis system. Mr Zhou reported having developed (with others) the AutoMorph retinal analysis system. Dr Trucco reported having developed (with others) the VAMPIRE retinal analysis system. Dr Mookiah reported having developed (with others) the VAMPIRE retinal analysis system. Dr MacGillivray reported having developed (with others) the VAMPIRE retinal analysis system. Mr Hogg reported having developed (with others) the VAMPIRE retinal analysis system. Dr Alexander reported having developed (with others) the AutoMorph retinal analysis system. Dr Stuart reported an overseas research scholarship from University College London and grants from Fight for Sight (London) 1956A and the Desmond Foundation during the conduct of the study. Dr Khawaja reported grants from Alcon and consultant fees from AbbVie, Aerie, Google Health, Novartis, Reichert, Santen, and Thea outside the submitted work. Dr Petzold reported royalties from Up-to-Date (Wolters Kluver) and a speaking fee from Heidelberg Academy. Dr Keane reported having developed (with others) the AutoMorph retinal analysis system and receiving personal fees from AbbVie, Google Health, Roche, Apellis, Novartis, RetinAI, and Bitfount and nonfinancial support from Bayer outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Retinal Images Representing Optical Coherence Tomography With the Retinal Nerve Fiber Layer (RNFL) and Macular Ganglion Cell–Inner Plexiform Layer (mGC-IPL) Indicated, the 9 Regions of the Early Treatment Diabetic Retinopathy Study (ETDRS) Grid Centered on the Fovea, and a Sample Color Fundus Photograph
Note that for variables from optical coherence tomography, only measurements from the inner ETDRS regions were included. The regions of the ETDRS grid are C, center; II, inner inferior; IN, inner nasal; IS, inner superior; IT, inner temporal; OI, outer inferior; ON, outer nasal; OS, outer superior; and OT, outer temporal.
Figure 2.
Figure 2.. Flowchart of Included Patients With Patient-Level and Image-Level Inclusion and Exclusion Criteria Detailed
See this image and copyright information in PMC

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