PURPOSE. To determine whether baseline cytokine aqueous humor (AH) levels are associated with diabetic macular edema (DME) anatomic response to dexamethasone intravitreal implant (DEX) injection. METHODS. This was a prospective cohort study of DME cases receiving DEX treatment. Seventy patients were recruited with center-involving DME with spectral-domain (SD) optical coherence tomography (OCT) detection of central macular thickness (CMT) ‡300 lm on macular cube 518 3 128-lm scan protocol (Cirrus SD-OCT). DEX injection and anterior chamber tap to obtain an AH sample were performed at the same time. Multiplex immunoassay was carried out for interleukin (IL)-1b, IL-3, IL-6, IL-8, IL-10; monocyte chemoattractant protein (MCP)-1; interferon gamma-induced protein (IP)-10; tumor necrosis factor (TNF)-a; and vascular endothelial growth factor (VEGF). A follow-up visit and OCT exam were undertaken 6 to 8 weeks afterward. The association between AH cytokine baseline levels and change in CMT and macular volume (MV) was defined as main outcome measure. RESULTS. Multivariate linear regression analysis showed a higher decrease in MV to be associated (R s of 0.512) with four baseline items: higher MCP-1 (b ¼ À0.4; P ¼ 0.028), higher CMT (b ¼ À0.003; P ¼ 0.024), decreased visual acuity (b ¼ À0.7; P ¼ 0.040), and a diffuse retinal thickening (DRT) OCT pattern (b ¼ À1.3; P < 0.001). Logistic regression found DRT also to be associated with higher odds of a good MV response (odds ratio, 31.96; 95% confidence interval [CI] 7.11-143.72; P < 0.001). CONCLUSIONS. Even though visual acuity response and anatomic effect are not always correlated in DME, we found that baseline elevated MCP-1 AH levels and DRT pattern were biomarkers that predicted a future favorable anatomic response to DEX.