Sex-Specific Changes in Choroid Vasculature Among Patients with Schizophrenia and Bipolar Disorder

Chloe Y Li,1,* Itika Garg,1,2,* Deepthi Bannai,3 Megan Kasetty,1 Raviv Katz,1,2 Iniya Adhan,3 Konstantinos AA Douglas,1 Jay C Wang,1 Leo A Kim,2 Matcheri Keshavan,3 Paulo Lizano,3,* John B Miller1,2,* 1Harvard Retinal Imaging Laboratory, Massachusetts Eye and Ear, Boston, MA, USA; 2Retina Service, Massachusetts Eye and Ear, Boston, MA, USA; 3Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA*These authors contributed equally to this workCorrespondence: John B Miller, Harvard Medical School, Department of Ophthalmology, Massachusetts Eye and Ear, 243 Charles St, Boston, MA, 02114, USA, Tel +1 617-573-3529, Email john_miller@meei.harvard.edu Paulo Lizano, Harvard Medical School, Department of Psychiatry, Beth Israel Deaconess Medical Center, 75 Fenwood Road, Room 612, Boston, MA, 02115, USA, Tel +1 617-754-1227, Email plizano@bidmc.harvard.eduPurpose: While structural changes within the retina of psychosis patients have been established, no detailed studies of choroidal microvasculature in these patients have been performed. Given evidence of microvascular disruption in psychosis patients, this study sought to determine whether there exists evidence of microvascular disruption in the choroids in these patients.Methods: Fifty-six subjects (20 controls and 36 psychosis patients) were recruited from April 2018 to February 2020. Five were excluded due to imaging artifact or missing demographic information. Swept-source optical coherence tomography angiography (SS-OCTA) images were obtained. Choroid vascular enface images (12 mm × 9mm) were exported every 2.6 μm from Bruch’s membrane to the choroid–scleral interface from Topcon to ImageJ. The images were binarized using Otsu’s method, signal from the optic disk and retinal vasculature was removed, and average choroid vascular density (CVD) was calculated as the average of percent area occupied by choroidal vasculature across images in the stack. Choroid vascular volume (CVV) was calculated as the CVD multiplied by maximum CT and image area. During image analysis, study staff were blinded to the phenotype of the study subjects.Results: Compared with same-sex controls, male psychiatric patients had significantly lower CVD. Compared with same-sex controls, female psychiatric patients had significantly lower maximum CT with correspondingly decreased CVV, after adjusting for age. When all psychiatric patients were compared with all healthy controls, no significant differences in CT, CVD, or CVV were noted.Conclusion: These results suggest that the pathogenesis of psychotic illness affects choroidal microvasculature in a sex-specific manner.Keywords: choroid vascular density, swept source optical coherence tomography angiography, psychosis, schizophrenia, bipolar disorder