Genetic, clinical, and biological risk factors associated with optic nerve thinning in sickle cell disease

Eye (Lond). 2026 May 6. doi: 10.1038/s41433-026-04318-2. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine whether adults with sickle cell disease (SCD) without glaucoma exhibit subclinical structural optic neuropathy (SON) 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 fibre layer (RNFL), and macular ganglion cell complex (GCC). SON 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. Haemoglobin correlated positively with BMO-MRW in HbSS (ρ = 0.41, p = 0.001), haematocrit 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 SON odds, whereas higher haemoglobin was protective.

CONCLUSIONS: Adults with SCD show OCT-detectable subclinical SON linked to genotype, retinopathy stage, anaemia severity, and vaso-occlusive burden; combined BMO-MRW, RNFL, and GCC may aid risk-stratified surveillance.

PMID:42092036 | DOI:10.1038/s41433-026-04318-2