BACKGROUND AND OBJECTIVE To determine whether optical density measurements of pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (AMD) can predict the response to treatment with anti-VEGF therapy. PATIENTS AND METHODS Retrospective review of SD-OCT scans of 21 eyes of 21 patients with neovascular AMD and PED. Response to treatment was determined using SD-OCT volumetric analysis. The authors used optical density measurements of PED lesions on SD-OCT images to calculate the serous index, which is a measure of the serous component of PEDs. RESULTS The serous index was found to correlate with the response to anti-VEGF treatment (r = .69, P = .0005), and to be predictive of the response to treatment (P = .007). CONCLUSION The serous index of PEDs can help predict the response to anti-VEGF treatment. This measure may be useful in decisions regarding switching anti-VEGF agents in the clinical care of patients with neovascular AMD and PED.