Serum Ang-1, sFLT-1, and sST2 Profiles Distinguish Anti-VEGF Responders in Diabetic Macular Edema

Abstract

Purpose: Diabetic macular edema (DME) remains a significant cause of vision loss despite the widespread use of anti-VEGF therapy. Nearly half of patients experience suboptimal responses in both anatomical and functional outcomes. This study correlates molecular signatures with clinical outcomes to identify associative markers of early treatment response and optimize DME management. Methods: Serum samples from 44 DME patients, treated with ≥3 anti-VEGF injections and 6 months follow-up, classified as responders or non-responders. Multiplex bead-based assays were used to measure cytokines related to vascular integrity, inflammatory, and adhesion molecules. Statistical analysis was performed using GraphPad. Results: Responders demonstrated improvement in BCVA from 20/63 (0.5 logMAR) to 20/35 (0.25 logMAR) and CRT (443 µm to 270 µm) (p < 0.01), while non-responders worsened in both parameters. The macular fluid area was 5-fold lower in responders (p < 0.001). Responders had higher Ang-1, sFLT-1, sST2, TNF-a, MCP-1( p< 0.01). Ang-1 and sFLT-1 correlated strongly with CRT reduction and improvement in BCVA. ROC analysis identified Ang-1, CRT (AUC = 0.9), and the Ang-1 ratio having superior diagnostic accuracy. Ang-1/sFLT-1 and Ang-1/sST2 ratios enhanced discrimination (AUC=0.9; p < 0.001). Conclusion: Ang-1, sFLT-1, and sST2 are closely associated with treatment response to anti-VEGF therapy in DME patients, highlighting their roles in vascular integrity, endogenous VEGF blockade, and inflammation regulation. Both the cytokines individual levels and their ratios serve as early indicators of the success of anti-VEGF treatment in DME. Integrating these cytokines with BCVA and CRT measurements could enhance the efficiency of DME management.