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To investigate the relationship of the pre–anti-vascular endothelial growth factor (VEGF) retinal tissue area (RTA) and optical density (ODRT) of the retinal optical slice portion located in the central subfield, and their ratio (RTA/ODRT), in the presence of diabetic macular edema or of inraretinal cystic fluid in neovascular age-related macular degeneration, to central retinal thickness and best-corrected visual acuity after anti-VEGF treatment with ME resolution.The optical coherence tomography images and medical records of 33 patients (41 eyes) with neovascular age-related macular degeneration, 15 (21 eyes) with diabetic macular edema and 9 healthy individuals (15 eyes) were retrospectively analyzed. RTA, ODRT, and RTA/ODRT were calculated on pre–anti-VEGF B-scan images. Spearman rank correlation was used to assess the relationship of central retinal thickness and best-corrected visual acuity after anti-VEGF treatment with the variables under study.Pre–anti-VEGF RTA was positively correlated with post–anti-VEGF central retinal thickness (ρ = 0.76; P < 0.001) and best-corrected visual acuity (ρ = 0.67; P < 0.001), whereas pre–anti-VEGF ODRT was moderately negatively correlated (ρ = −0.26; P = 0.049 and ρ = −0.48; P = 0.001, respectively) and pre–anti-VEGF RTA/ODRT ratio was strongly positively correlated (ρ = 0.75; P < 0.001 and ρ = 0.85; P < 0.001, respectively). The area under curve for RTA/ODRT ratio was 0.93 (P < 0.001), and the cut-off value for post–anti-VEGF LogMAR best-corrected visual acuity of 0.4 (20/50 Snellen equivalent) or worse was 1,406.7 μm2/U (sensitivity: 0.94; specificity: 0.78).Both RTA and ODRT, or, preferably, RTA/ODRT ratio alone can be used as predictors of functional and anatomic outcomes in patients with diabetic macular edema or neovascular age-related macular degeneration treated with anti-VEGF therapy.