The role of red blood cell characteristics and viscosity in sickle cell retinopathy and maculopathy

Sickle cell disease (SCD), encompassing genotypes such as HbSS and HbSC, causes chronic haemolysis and microvascular occlusion, leading to organ damage. The retina is particularly vulnerable, often resulting in sickle cell retinopathy (SCR) or sickle cell maculopathy (SCM). The precise underlying mechanisms are unclear, though various factors are suggested to contribute. This study explored the role of whole blood viscosity and red blood cell (RBC) deformability in SCR and SCM. Adult HbSS (n = 34) and HbSC patients (n = 34) were offered an ophthalmic examination to determine SCR stage. A venous ethylenediaminetetraacetic acid (EDTA) sample was collected from each participant. Whole blood viscosity was measured using a Brookfield viscometer and RBC deformability was assessed using the Oxygenscan feature of the Laser Optical Rotational Red Cell Analyser as a function of the (varying) partial oxygen pressure. HbSC patients with proliferative sickle cell retinopathy (PSCR) had a lower delta elongation index (p = 0.012) and point of sickling (p = 0.002) than those without PSCR, suggesting that RBC sickling might not play a central role in the pathogenesis of PSCR in HbSC patients. Despite hyperviscosity being a commonly proposed mechanism, no associations were found between blood viscosity, SCR and SCM. These results point to alternative mechanisms contributing to SCR and SCM, highlighting the complexity and need for further research to fully understand the underlying factors.