Assessment of retinal neurodegeneration in metabolic syndrome and its vascular determinants

Abstract Purpose To evaluate retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) thickness in individuals with and without metabolic syndrome and examine associations with vascular risk factors. Methods In this prospective cross‐sectional study, adults without ocular disease undergoing cardiovascular risk assessment were examined using spectral‐domain optical coherence tomography (RTVue XR Avanti). RNFL and GCC thickness were measured. Associations between systemic factors and retinal layer thickness were analysed using linear regression with generalized estimating equations, stratified by metabolic syndrome status. Results Among 209 participants (median age (IQR) 52 (49–56) years; 56% female), 110 (53%) had metabolic syndrome. RNFL and GCC thickness did not differ significantly by metabolic syndrome status ( p > 0.05). In those with metabolic syndrome, higher mean arterial pressure (MAP; β = −0.18 μm/mmHg, p = 0.007), greater carotid intima‐media thickness ( β = −0.02 μm/μm, p = 0.006) and smoking ( β = −4.10 μm, p = 0.040) were associated with thinner RNFL. Similarly, higher MAP ( β = −0.17 μm/mmHg, p < 0.001) and smoking ( β = −5.72 μm, p < 0.001) were associated with thinner GCC. In participants without metabolic syndrome, no significant associations were observed for RNFL (all p > 0.05), while thinner GCC was associated with higher BMI ( β = −0.47 μm/kg/m 2 , p = 0.036) and higher urine albumin ( β = −0.03 μm/mg/L, p < 0.001). Across all participants, smoking was associated with thinner GCC ( β = −4.79 μm, p < 0.001). Conclusions In this cardiovascular high‐risk but ocular disease‐free cohort, vascular factors, rather than metabolic syndrome itself, were associated with thinner RNFL and GCC. These findings suggest that vascular stress may contribute to early retinal neurodegeneration.