Genetic, Clinical, and Biological Risk Factors Associated with Optic Nerve Thinning in Sickle Cell Disease.

Abstract Objectives To determine whether adults with sickle cell disease (SCD) without glaucoma exhibit subclinical optic neuropathy (ON) on optical coherence tomography (OCT) and to identify genetic, clinical, and biologic correlates of optic nerve thinning. Methods Monocentric, retrospective cross-sectional study of 185 eyes from 96 adults with SCD (116 eyes/59 HbSS; 69 eyes/37 HbSC) and 40 eyes from 20 controls. Spectral-domain OCT measured Bruch’s membrane opening–minimum rim width (BMO-MRW), peripapillary retinal nerve fiber layer (RNFL), and macular ganglion cell complex (GCC). ON was defined as concordant thinning across all three parameters. Patient-clustered models with Holm adjustment compared groups; multivariable clustered logistic regression identified risk factors. Results Compared with controls, SCD eyes showed thinner BMO-MRW, RNFL, and GCC (all p < 0.001). Within SCD, HbSC exhibited greater thinning than HbSS, especially in temporal and superonasal BMO-MRW sectors and RNFL average, inferotemporal, and superotemporal sectors. Proliferative SCR showed more pronounced loss than non-proliferative disease, including lower BMO-MRW, temporal RNFL thinning, and global GCC reduction. Hemoglobin correlated positively with BMO-MRW in HbSS (ρ = 0.41, p = 0.001), hematocrit tended toward a negative association with RNFL in HbSC (ρ=−0.29, p = 0.06), and reticulocytes were inversely associated with GCC in HbSS (ρ=−0.25, p = 0.038) and HbSC (ρ=−0.31, p = 0.038). Older age, recent acute chest syndrome, and ≥ 1 vaso-occlusive crisis within 2 years independently increased ON odds, whereas higher hemoglobin was protective. Conclusions Adults with SCD show OCT-detectable subclinical ON linked to genotype, retinopathy stage, anemia severity, and vaso-occlusive burden; combined BMO-MRW, RNFL, and GCC may aid risk-stratified surveillance.