OBJECTIVES: To determine real-life quantitative changes in OCT biomarkers in a large set of treatment naive patients in a real-life setting undergoing anti-VEGF therapy. For this purpose, we devised a novel deep learning based semantic segmentation algorithm providing the first benchmark results for automatic segmentation of 11 OCT features including biomarkers for neovascular age-related macular degeneration (nAMD). METHODS: Training of a Deep U-net based semantic segmentation ensemble algorithm for state-of-the-art semantic segmentation performance which was used to analyze OCT features prior to, after 3 and 12 months of anti-VEGF therapy. RESULTS: High F1 scores of almost 1.0 for neurosensory retina and subretinal fluid on a separate hold-out test set with unseen patients. The algorithm performed worse for subretinal hyperreflective material and fibrovascular PED, on par with drusenoid PED, and better in segmenting fibrosis. In the evaluation of treatment naive OCT scans, significant changes occurred for intraretinal fluid (mean: 0.03 µm3 to 0.01 µm3, p < 0.001), subretinal fluid (0.08 µm3 to 0.01 µm3, p < 0.001), subretinal hyperreflective material (0.02 µm3 to 0.01 µm3, p < 0.001), fibrovascular PED (0.12 µm3 to 0.09 µm3, p = 0.02) and central retinal thickness C0 (225.78 µm3 to 169.40 µm3). The amounts of intraretinal fluid, fibrovascular PED, and ERM were predictive of poor outcome. CONCLUSIONS: The segmentation algorithm allows efficient volumetric analysis of OCT scans. Anti-VEGF provokes most potent changes in the first 3 months while a gradual loss of RPE hints at a progressing decline of visual acuity. Additional research is required to understand how these accurate OCT predictions can be leveraged for a personalized therapy regimen.