Abstract : This paper addresses the problem of automatic classification of Spectral Domain OCT (SD-OCT) data for automatic identification of patients with Diabetic Macular Edema (DME) versus normal subjects. Optical Coherence Tomography (OCT) has been a valuable diagnostic tool for DME, which is among the most common causes of irreversible vision loss in individuals with diabetes. Here, a classification framework with five distinctive steps is proposed and we present an extensive study of each step. Our method considers combination of various pre-processings in conjunction with Local Binary Patterns (LBP) features and different mapping strategies. Using linear and non-linear classifiers, we tested the developed framework on a balanced cohort of 32 patients. Experimental results show that the proposed method outperforms the previous studies by achieving a Sensitivity (SE) and Specificity (SP) of 81.2% and 93.7%, respectively. Our study concludes that the 3D features and high-level representation of 2D features using patches achieve the best results. However, the effects of pre-processing is inconsistent with respect to different classifiers and feature configurations.