Retinal Microvascular Alterations in Sickle Cell Disease: A Systematic Review and Meta-Analysis of Octa Findings Based on Genotype and Stages of Retinopathy Publisher Pubmed



Amanollahi M ; Mozafar M ; Farrokhpour H ; Gouravani M ; Samiee R ; Amiri F ; Rezaei S ; Rasouli S ; Jameie M ; Mozafar N ; Pour EK ; Zhang AY
Source: Graefe's Archive for Clinical and Experimental Ophthalmology Published:2026

Abstract

Purpose: Sickle cell disease (SCD) is one of the most prevalent genetic disorders that notably impacts the retinal microvasculature. This study aims to conduct a systematic review and meta-analysis of studies on optical coherence tomography angiography (OCTA) measurements in SCD. Methods: A systematic search was performed through PubMed and Embase from the earliest record until July 2024. Data extraction was performed considering the important characteristics of the studies’ populations (e.g., genotype and sickle cell retinopathy (SCR)) and OCTA measurements (e.g., vessel density (VD) and foveal avascular zone (FAZ)). Quantitative synthesis was conducted on the metrics assessed in at least two studies with comparable study populations. Results: Thirty-one studies were included. There was a significant increase in FAZ in SCD patients compared to the controls (Hedge’s g = 0.72, CI = 0.43 to 1.01, p < 0.001). However, the superficial capillary plexus (SCP) VD showed no significant differences for the foveal, parafoveal area, and each parafoveal sector, except for a lower VD in the temporal parafoveal area in SCD compared to the control (Hedge’s g = -0.58, CI = -0.99 to -0.18, p = 0.01). Meta-analysis revealed significantly smaller values for deep capillary plexus (DCP) VD in all parafoveal subregions (p < 0.05), except for the inferior, in patients than in controls. Concerning genotype differences, whole DCP VD (but not SCP VD) was significantly lower in the hemoglobin SS (HbSS) genotype than in controls (Hedge’s g = -1.51, CI = -2.33 to -0.68, p < 0.001). Meta-analysis demonstrated a nonsignificant increase in FAZ size in HbSC compared to HbSS (Hedge’s g = -0.19, CI = -0.63 to 0.25, P = 0.39). Conclusion: This review demonstrates retinal microvasculature alterations in SCD patients, affected by SCR and the disease genotype. The changes were more notable in the temporal subfield, aligning with reported temporal retinal thinning. DCP appeared more susceptible to ischemia than SCP, with stronger changes in HbSS. Heterogeneity in OCTA parameters, genotype distribution, and SCR stage limited conducting meta-analysis on all studies. Future studies should encompass different standardized OCTA parameters and SCD populations regarding SCR and genotype. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2026.