Paramacular thinning in homozygous sickle cell disease is correlated with systemic markers of disease severity

Abstract

Purpose : Cerebral vasculopathy is the most severe complication of homozygous sickle cell disease (SCD) in children. Recently, the paramacular atrophy of the inner retinal layers found on optical coherence tomography (OCT) in SCD has been suggested to represent a retinal equivalent of silent cerebral infarcts. We performed a prospective clinical pilot study to look for correlations between the retinal thickness and neurological and systemic markers of the severity of SCD.

Methods : Seventeen children (12 girls) with homozygous SCD, clinically stable at the time of inclusion, were included. The mean age was 13 years (SD=3.7). Patients with a past history of stroke, patients having been or presently included in a transfusion program, and patients with a history of abnormal transcranial Doppler, were not included. The following data were collected: past medical history; hematological, hemolysis and hemorrheological parameters extracted from a single blood sample; estimation of brain oxygenation with cerebral oxymetry using near infrared spectroscopy; retinal thickness measurements with OCT scans along the temporal median raphe. Comparisons of means were made with Mann-Whitney test and correlations were obtained with Spearman and Pearson tests.

Results : Eight children (38% of eyes) were found with areas of paramacular atrophy on OCT. Red cell deformability was found significantly lower in children with atrophy (p=0.01), as well as cerebral oxymetry (p=0.02). Children with atrophy were also found with a tendency of higher hemolysis parameters (aspartate aminotransferase: 28.9 vs 18.4, p=0.008). Regardless of the presence of areas of paramacular atrophy, the average retinal thickness between right and left eyes at 4000µm temporally from the fovea was significantly correlated positively with red cells deformability (ρ=0.69, p=0.01), and inversely with several hemolysis parameters (alanine aminotransferase: ρ=-0.54, p=0.03). A significant correlation was also found between temporal retinal thickness and cerebral oxymetry (ρ=0.50, p=0.04).

Conclusions : In children with homozygous SCD, decreased retinal thickness is correlated with systemic markers of the disease severity. These results suggest that paramacular retinal atrophy is a witness of a decrease in the brain oxygenation, and therefore offers the potential for being used as a biomarker for the early detection of cerebral vasculopathy in SCD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.