AbstractDrusen are an important biomarker for age-related macular degeneration (AMD). Their accurate segmentation based on optical coherence tomography (OCT) is therefore relevant to the detection, staging, and treatment of disease. Since manual OCT segmentation is resource-consuming and has low reproducibility, automatic techniques are required. In this work, we introduce a novel deep learning based architecture that directly predicts the position of layers in OCT and guarantees their correct order, achieving state-of-the-art results for retinal layer segmentation. In particular, the average absolute distance between our model’s prediction and the ground truth layer segmentation in an AMD dataset is 0.63, 0.85, and 0.44 pixel for Bruch's membrane (BM), retinal pigment epithelium (RPE) and ellipsoid zone (EZ), respectively. Based on layer positions, we further quantify drusen load with excellent accuracy, achieving 0.994 and 0.988 Pearson correlation between drusen volumes estimated by our method and two human readers, and increasing the Dice score to 0.71 ± 0.16 (from 0.60 ± 0.23) and 0.62 ± 0.23 (from 0.53 ± 0.25), respectively, compared to a previous state-of-the-art method. Given its reproducible, accurate, and scalable results, our method can be used for the large-scale analysis of OCT data.