The Association of Sickle-Cell Disorders With Diabetic Retinopathy: A Large Database Study

Purpose: To evaluate the association of sickle-cell disease (SCD) and sickle-cell trait (SCT) disease with diabetic retinopathy (DR) in patients with diabetes mellitus (DM).

Design: Population-based, retrospective cohort study utilizing data from the TriNetX Research Network, including 119 million patients across 80 health care organizations worldwide.

Participants: Diabetes mellitus patients (type 1 [T1DM] or 2 [T2DM]), with or without SCD and SCT, were included. Three cohorts were analyzed, including (1) DM patients without SCD, SCT, or sickle-cell/hemoglobin-C; (2) DM with SCD; and (3) DM with SCT.

Methods: All patients with DM were categorized into 3 cohorts based on the presence of SCD and SCT. Each cohort underwent 1:1 propensity score matching for demographics, blood glucose levels, hemoglobin A1C, and other relevant comorbidities.

Main outcome measures: Risk of DR in DM patients with and without SCD or SCT.

Results: There was no significant difference in the risk of any T1DR between those with and without SCD. However, for those with SCT, there was a notable twofold increased risk for T1-proliferative DR (PDR) (relative risk [RR]: 2.03; 95% confidence interval [CI]: 1.33-3.01). In contrast, there was an elevated risk for any T2DR in patients with SCD (RR: 1.50; 95% CI: 1.19-1.88), particularly due to higher PDR risks in T2DM patients (RR: 1.83; 95% CI: 1.29-2.60). The risk of mild to moderate T2DM non-PDR was also found to be higher in patients with SCT.

Conclusions: The risk of any DR was increased in T2DM patients with SCD or SCT, with increased risks for PDR in patients with SCT and T1DM. This indicates there may be a potential role of sickle-cell disorders in diabetic eye disease progression.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.