Aqueous Cytokine Expression and Higher-Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study

Abstract Purpose To identify biomarkers for predicting response to anti-VEGF therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and OCT phenotype. Design IMAGINE DME is a post-hoc image analysis and cytokine expression assessment of the DAVE randomized clinical trial. Methods Subjects were categorized as anatomical Responders or Nonresponders,and within the Responder group as Rebounders and Nonrebounders based on quantitative, longitudinal optical coherence tomography (OCT) criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines at multiple timepoints. Expression was compared between Responder groups and correlated with OCT imaging biomarkers. Results Of the 24 eyes studied, 79% were anatomical Responders with 38% Super Responders, 17% Early Responders, 25% Slow Responders. Twenty-one percent were Nonresponders. Super Responders had increased baseline VEGF (880.0 vs 245.4 pg/mL, p=0.012) and decreased MCP-1 (513.3 vs 809.5 pg/mL, 0.042) concentrations compared to Nonresponders. IL-6 (-24.9 vs 442.8 pg/mL, p=0.032) concentrations increased among Nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r=0.49, p=0.01). Panmacular retinal volume correlated with increased IL-6 (r=0.47, p=0.02) and decreased MCP-1 (r=-0.45, p=0.03). MMP-1 correlated with SRF volume (r=0.50, p=0.01). Conclusions OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, indicating a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.