Serum–vitreous biomarker ratios of RBP3, IBA-1, and VEGFA in proliferative diabetic retinopathy: an age-stratified analysis

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Proliferative diabetic retinopathy (PDR) is an advanced neurovascular complication of diabetes mellitus that can result in irreversible visual loss. This study evaluated serum and vitreous concentrations of vascular endothelial growth factor A (VEGFA), ionized calcium-binding adapter molecule 1 (IBA-1), and retinol-binding protein 3 (RBP3), their ratios, and their associations with PDR and age.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This analytical observational cross-sectional study included 30 patients with high-risk PDR undergoing pars plana vitrectomy and 10 nondiabetic controls undergoing vitrectomy for non-diabetic vitreoretinal conditions. Vitreous and serum samples were analyzed using enzyme-linked immunosorbent assays. Biomarker concentrations and ratios were compared between groups, and associations were assessed using nonparametric tests, logistic regression, and ridge-regularized logistic regression. Age-stratified analyses used three predefined groups: &lt;45, 45–60, and &gt; 60 years.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> Patients with PDR had significantly higher vitreous and serum IBA-1 concentrations, higher vitreous VEGFA concentrations, and lower vitreous RBP3 concentrations than controls (all <jats:italic>p</jats:italic>  ≤ 0.014). Vitreous RBP3/IBA-1 and RBP3/VEGFA showed the strongest inverse associations with PDR. Vitreous IBA-1 demonstrated the strongest discrimination between the PDR and control groups (AUC = 1.000), followed by the vitreous RBP3/IBA-1 ratio (AUC = 0.993). Age-stratified analysis showed significant differences in vitreous IBA-1 concentrations across the &lt; 45, 45–60, and &gt; 60-year groups, with the highest concentrations observed in the &gt; 60-year group. No significant age-group differences were observed for vitreous VEGFA or RBP3. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Serum and vitreous IBA-1, VEGFA, and RBP3 profiles were associated with PDR, supporting the involvement of inflammatory, angiogenic, and neuroprotective pathways. The RBP3/IBA-1 and RBP3/VEGFA ratios may provide complementary information regarding these interacting pathways. Vitreous IBA-1 showed the strongest discrimination between the PDR and nondiabetic control groups within this cohort, while age-stratified analysis demonstrated significant differences in vitreous IBA-1 across age groups. These exploratory findings should be interpreted cautiously given the small sample size, the very high within-cohort discriminatory performance, and the absence of external validation. Validation in larger, age-matched, independent, and longitudinal cohorts is required to establish the reproducibility and clinical relevance of these biomarkers before considering any diagnostic or prognostic application.</jats:p> </jats:sec>