Retinal Thinning Starts in Childhood in Sickle Cell Disease Patients

Thickness decreased over time in multiple parafoveal and perifoveal subfields in the inner retina, as well as multiple perifoveal subfields in the middle and total retina in the HbSS group, suggesting that microstructural and microvasculature abnormalities in the macula start in childhood in sickle cell disease. These ETDRS grids from the study show change per year for inner retinal thickness, SCP vessel density and DCP vessel density within HbSS and HbS Variant subjects. Red represents decrease with p<0.05, yellow represents decrease between p<0.1 and ≥0.05, green represents increase with p<0.05, while lime represents increase between p<0.1 and ≥0.05. Photo: Ong SS, et al. Ophthalmol Sci. June 24, 2025. Click image to enlarge. Researchers recently assessed longitudinal changes in retinal thickness and vessel density (VD) in pediatric sickle cell disease. They found progressive retinal thinning, predominantly in the inner retinal layers, was particularly notable in children with the HbSS genotype, suggesting that microstructural and microvasculature abnormalities in the macula start in childhood in sickle cell disease. The findings were reported in Ophthalmology Science.A total of 28 children (56 eyes) ages 18 and younger with HbSS and HbS variant genotypes were enrolled from a university-based retina subspecialty clinic and followed for at least two years. They received OCT and OCT-A scans at baseline and each follow-up visit comparing retinal thickness, superficial capillary plexus (SCP) and deep capillary plexus (DCP) VD over time.The same authors previously reported that HbSS children had qualitative retinal thinning compared to age-matched controls, although this was not observed when measurements of retinal thickness were quantitatively analyzed. In this follow-up longitudinal study, they found that retinal thickness decreased over time in both the parafoveal (inner retina) and perifoveal (inner, middle and total retina) regions for children with HbSS disease but mostly did not change over time in children with the HbS variant subtype. This is consistent with prior reports that showed that retinal thinning was most severe in patients with the HbSS subtype and that most retinal thinning was associated with retinal nerve fiber layer thinning.“Our results provide further support for the hypothesis that retinal thinning starts early in childhood in patients with HbSS disease compared to those with the HbS variant genotype,” the authors wrote in their paper in Ophthalmology Science. “By adulthood, retinal thinning may not progress as quickly in patients with HbSS compared to those with HbS variant disease since the former started with thinner retinas from childhood.”The authors’ first study showed that, compared to matched controls, HbSS children had lower VD in the deep capillary plexus but not the superficial layer, while HbS variant children had lower vessel density in both. The current study found similar vessel density increases over time, for the most part. “We speculate that this either represents a compensatory increase due to lower values at baseline or is part of normal growth during childhood, or both,” the authors explained in their article.Given prior evidence that vascular density both in the DCP and SCP physiologically increases in normal childhood until adolescence, these results show that this process is disrupted in the SCP in HbSS children, the authors explained. “We postulate that this is due to the severe sickling crisis in the macular microvasculature that can disproportionately affect the inner retina in HbSS disease, and which can start in infancy. This would also contribute to the disproportionate thinning of the inner retina over time.”Demographic and ocular characteristics did not differ across groups, but lower hemoglobin levels and higher rates of cerebrovascular accidents were observed for the HbSS group, reflecting more severe systemic manifestations in HbSS disease when compared to the HbS variant genotype, the authors noted.The authors suggest that clinicians should consider systemic disease-modifying therapies in children with sickle cell disease at an early age before permanent anatomic changes occur in the retina.Click here for the journal source. Ong SS, Nampomba A, Rahman S, et al. Macular thinning and microvasculature abnormalities in children with sickle cell disease: a longitudinal analysis. Ophthalmol Sci. June 24, 2025. [Epub ahead of print.]