Circulating angiogenesis‐related biomarkers in sickle cell retinopathy and maculopathy

Sickle cell disease (SCD), encompassing genotypes such as HbSS and HbSC, leads to retinal complications such as sickle cell retinopathy (SCR) and maculopathy (SCM) through poorly understood mechanisms. This study explored associations of a panel of circulating angiogenesis-related factors with SCR and SCM. Adult HbSS (homozygous SCD; n = 33) and HbSC (compound heterozygous SCD; n = 33) patients underwent ophthalmic examination, including optical coherence tomography angiography, to assess SCR stage and presence of SCM. Plasma levels of circulating angiogenesis-related factors were analysed, with selected markers (angiopoietin-2, vascular endothelial growth factor [VEGF], granulocyte colony-stimulating factor, endoglin, endostatin, interleukin [IL]-6 and IL-10) assessed using enzyme-linked immunosorbent assay. Proliferative SCR (PSCR) was present in 5 (15.2%) HbSS and 21 (63.6%) HbSC patients. Foveal avascular zone abnormalities and macular thinning were present in 50.8% and 48.4% of patients respectively. Most vascular factors, including VEGF, showed no association with SCR or SCM. However, angiopoietin-2 was higher in HbSS patients, independent of SCR stage or SCM, and correlated with IL-6, IL-10, VEGF, reticulocyte counts, and lactate dehydrogenase (LDH). In HbSC patients, endostatin levels were highest in those with PSCR (p = 0.030). While most proteins were unrelated to retinal outcomes, angiopoietin-2 elevation may reflect HbSS-specific systemic hypoxia. Elevated endostatin in HbSC patients with PSCR suggests a potential role in PSCR development. These findings offer new leads for understanding SCD-related retinal disease.