Aqueous Interleukin-6 (IL-6) Level Is a Marker for Treatment Resistance to Bevacizumab in Age-Related Macular Degeneration —Aqueous Cytokines after Bevacizumab

Background: To prospectively evaluate the effect of intravitreal bevacizumab on aqueous levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in patients with exudative age-related macular degeneration (AMD) and to correlate clinical outcomes of patients and aqueous cytokine levels before and after injection. Methods: The study group consisted of 30 eyes from 30 patients with exudative AMD who underwent intravitreal injection of bevacizumab three times at monthly intervals. The aqueous samples prior to the 1st injection (baseline) and 3rd injection were analyzed for VEGF and IL-6 levels, evaluating the effect of 2 doses of intravitreal bevacizumab. Study patients were sub-grouped based upon change in central subfield (CSF) macular thickness on SD-OCT, at 8 weeks. Group 1 included patients (n = 14) with a decrease in CSF thickness greater than 10% from the baseline and were categorized to have “improved”. Group 2 included patients (n = 16) who had a decrease in CSF thickness 10% or less and were considered “treatment-resistant”. Results: There was no statistically significant change in aqueous VEGF and IL-6 levels after intravitreal bevacizumab. In sub-group analysis, in both Groups 1 and 2 patients, aqueous IL-6 levels showed a better correlation with CSF thickness on SD-OCT (r = 0.72 and 0.71, respectively). Conclusions: Data from our study suggest that aqueous IL-6 may be an important marker of treatment response or resistance. Future therapeutic strategies may include targeted treatment against both VEGF and IL-6, in patients who do not respond to anti-VEGF treatment alone.