UC San Diego

OBJECTIVE: To quantitatively assess the retinal vascular tortuosity of patients with sickle cell disease (SCD) and retinopathy (SCR) using an automated deep learning (DL)-based pipeline. DESIGN: Cross-sectional study. SUBJECTS: Patients diagnosed with SCD and screened for SCR at an academic eye center between January 2015 and November 2022 were identified using electronic health records. Eyes of unaffected matched patients (i.e., no history of SCD, hypertension, diabetes mellitus, or retinal occlusive disorder) served as controls. METHODS: For each patient, demographic data, sickle cell diagnosis, types and total number of sickle cell crises, SCD medications used, ocular and systemic comorbidities, and history of intraocular treatment were extracted. A previously published DL algorithm was used to calculate retinal microvascular tortuosity using ultrawidefield pseudocolor fundus imaging among patients with SCD vs. controls. MAIN OUTCOME MEASURES: Cumulative tortuosity index (CTI). RESULTS: Overall, 64 patients (119 eyes) with SCD and 57 age- and race-matched controls (106 eyes) were included. The majority of the patients with SCD were females (65.6%) and of Black or African descent (78.1%), with an average age of 35.1 ± 20.1 years. The mean number of crises per patient was 3.4 ± 5.2, and the patients took 0.7 ± 0.9 medications. The mean CTI for eyes with SCD was higher than controls (1.06 ± vs. 1.03 ± 0.02, P < 0.001). On subgroup analysis, hemoglobin S, hemoglobin C, and HbS/beta-thalassemia variants had significantly higher CTIs compared with controls (1.07 vs. 1.03, P < 0.001), but not with sickle cell trait variant (1.04 vs. 1.03 control, P = .2). Univariable analysis showed a higher CTI in patients diagnosed with proliferative SCR, most significantly among those with sea-fan neovascularization (1.06 ± 0.02 vs. 1.04 ± 0.01, P < 0.001) and those with >3 sickle cell crises (1.07 ± 0.02 vs. 1.05 ± 0.02, P < 0.001). CONCLUSIONS: A DL-based metric of cumulative vascular tortuosity associates with and may be a potential biomarker for SCD and SCR disease severity. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.