Systemic metabolic dysfunction is associated with local treatment failure: the role of visceral adiposity index in anti-VEGF resistance in diabetic macular edema

Background A substantial number of patients with diabetic macular edema (DME) exhibit resistance to standard anti-vascular endothelial growth factor (anti-VEGF) therapy, representing a major clinical challenge. The Visceral Adiposity Index (VAI), a surrogate for visceral fat dysfunction and systemic metabolic derangement, has been linked to diabetic microvascular complications, but its power to serve as a prognostic marker for local therapeutic failure in DME is unknown. This study aimed to determine if baseline VAI, as a marker of systemic metabolic dysfunction, is associated with resistance to intravitreal anti-VEGF therapy in patients with DME. Methods This retrospective cohort study analyzed 298 patients with type 2 diabetes and center-involved DME initiating anti-VEGF therapy between January 2022 and December 2023. VAI was calculated at baseline. The primary outcome was a positive functional response, defined by pre-specified Best-Corrected Visual Acuity (BCVA) improvements at 24 months. Patients not meeting these criteria were classified as exhibiting treatment resistance. Multivariable logistic regression identified independent factors associated with response, ROC curve analysis assessed VAI’s prognostic performance, and Kaplan-Meier analysis evaluated time-to-response. Results Patients with treatment resistance (non-responders, 47.0%) had significantly higher baseline VAI scores than responders (4.4 ± 3.0 vs. 2.4 ± 1.9, p<0.001). After adjusting for confounders, a higher VAI was independently associated with a greater likelihood of treatment failure (Adjusted OR for positive response = 0.71 per unit increase; 95% CI: 0.61–0.82; p<0.001). VAI demonstrated acceptable prognostic ability for resistance (AUC = 0.73), with an optimal cut-off of 2.50. Patients with VAI ≥2.50 had a significantly lower and delayed probability of achieving a positive response (log-rank p < 0.0001). Conclusion Baseline VAI is a potent, independent prognostic marker associated with local treatment failure in response to anti-VEGF therapy in DME. This study demonstrates that a measure of systemic metabolic dysfunction can correlate with the efficacy of a localized treatment. VAI is an easily calculated, non-invasive index that can effectively risk-stratify patients, identifying those who may require more intensive or alternative management strategies from the outset to overcome this metabolic resistance.