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. 2025 Jun;206(6):1796-1805.
doi: 10.1111/bjh.20124. Epub 2025 Apr 29.

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

Rajani P Brandsen  1   2 , Roselie M H Diederen  1 , Ingeborg Klaassen  3 , Martijn Veldthuis  4 , Herbert Korsten  5 , Rob van Zwieten  4 , Reinier O Schlingemann  1   3   6 , Erfan Nur  2   7 , Bart J Biemond  2
Affiliations

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

Rajani P Brandsen et al. Br J Haematol. 2025 Jun.

Abstract

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.

Keywords: erythrocyte deformability; sickle cell disease; sickle cell maculopathy; sickle cell retinopathy; viscosity.

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Conflict of interest statement

RPB has received research grants from Stichting Pupil (Pupil Foundation, the Netherlands), Stichting UitZicht (UitZicht Foundation, the Netherlands), Het Sikkelcelfonds (the Netherlands), the Maarten Kappelle Stichting (the Netherlands) and the Rotterdamse Stichting Blindenbelangen (the Netherlands). ROS has received research grants from Novartis and Boeringer‐Ingelheim and participated in advisory board meetings of Apellis, Boeringer‐Ingelheim and Ciana Therapeutics. EN has received a research grant from Novartis and participated in the advisory board and speakers' bureau of Novartis. BJB has received research grants from Sanquin, Novartis, GBT/Pfizer and BMS/Celgene; participated in advisory board meetings of BMS/Celgene, Novo Nordisk and GBT/Pfizer; and received honoraria from Sanofi and Novo Nordisk. RMHD and IK have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
Illustration of normal and abnormal spectral‐domain coherence tomography (SD‐OCT) and optical coherence tomography angiography (OCTA) scans. (A, B) A normal SD‐OCT scan (A) with a completely green Early Treatment Diabetic Retinopathy Study (ETDRS) circle (B), indicating normal macular thickness. An example of a normal OCTA scan is shown in (C), displaying the typical macular vascular structure with clearly defined white vessels and a round, well‐formed foveal avascular zone (FAZ) at the centre of the macula, indicative of normal retinal vasculature. (D, E) An SD‐OCT scan with macular thinning. The yellow arrows in (D) show the focal areas of macular thinning. (E) The corresponding ETDRS circle, with several blue segments indicating macular thinning. The OCTA scan shown in (F) demonstrates an irregularly enlarged border of the foveal avascular zone, indicating local vascular loss (yellow arrow).
FIGURE 2
FIGURE 2
Hypothesised pathophysiology of sickle cell retinopathy and maculopathy. This diagram illustrates the sequence of events leading to sickle cell retinopathy and maculopathy, highlighting the complex interactions between sickling, blood viscosity and retinal damage. It depicts how these factors are hypothesized to contribute to the development and progression of the conditions.
See this image and copyright information in PMC

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