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In diabetic patients presenting with macular edema (ME) shortly after cataract surgery, identifying the underlying pathology can be challenging and influence management. Our aim was to develop a simple clinical classifier able to confirm a diabetic etiology using few spectral domain optical coherence tomography parameters.We analyzed spectral domain optical coherence tomography data of 153 patients with either pseudophakic cystoid ME (n = 57), diabetic ME (n = 86), or “mixed” (n = 10). We used advanced machine learning algorithms to develop a predictive classifier using the smallest number of parameters.Most differentiating were the existence of hard exudates, hyperreflective foci, subretinal fluid, ME pattern, and the location of cysts within retinal layers. Using only 3 to 6 spectral domain optical coherence tomography parameters, we achieved a sensitivity of 94% to 98%, specificity of 94% to 95%, and an area under the curve of 0.937 to 0.987 (depending on the method) for confirming a diabetic etiology. A simple decision flowchart achieved a sensitivity of 96%, a specificity of 95%, and an area under the curve of 0.937.Confirming a diabetic etiology for edema in cases with uncertainty between diabetic cystoid ME and pseudophakic ME was possible using few spectral domain optical coherence tomography parameters with high accuracy. We propose a clinical decision flowchart for cases with uncertainty, which may support the decision for intravitreal injections rather than topical treatment.