Exploring systemic erythropoietin in diabetic retinopathy: Longitudinal associations and biomarker potential in the LANDMark cohort

Aims Diabetes mellitus (DM) is a chronic, multifactorial disease with systemic effects, demanding ongoing clinical vigilance and risk-reduction strategies. Among its most prevalent microvascular complications is diabetic retinopathy (DR), affecting 30–40% of individuals with DM and associated with sustained hyperglycaemia. This study investigates the role of erythropoietin (EPO), a glycoprotein primarily known for its role in erythropoiesis, in retinal pathology. Methods Secondary analysis was conducted on 117 participants from the Australian cohort of the LANDMark study, examining the relationship between systemic EPO levels and DR severity, as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Severity Scale. Results Significant positive correlations were observed between serum EPO and DR severity at both baseline and the four-year follow-up (baseline: ρ = 0.212, p = 0.025; four-year ρ = 0.205, p = 0.030). Ordinal regression indicated that both baseline and four-year EPO levels were associated with higher DR severity at the four-year follow-up (baseline: log-odds coefficient = 2.258, OR ≈ 9.57, p < 0.01; four-year: log-odds coefficient = 2.111, OR ≈ 8.26, p = 0.01). Conclusion These findings suggest that systemic EPO shows a modest association with subsequent retinopathy severity and may reflect an exploratory biomarker of ocular disease activity.