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To quantify the foveal avascular zone area at superficial capillary plexus (SCP) and deep capillary plexus (DCP) and the global, parafoveal, and perifoveal vessel densities at SCP, DCP, and choriocapillaris using optical coherence tomography angiography in patients affected by adult-onset foveomacular vitelliform dystrophy (AOFVD).Twenty eyes of 20 consecutive patients (10 females, 50%) with AOFVD and 20 eyes of 20 healthy controls presenting at the Department of Ophthalmology of San Raffaele Hospital, Milan, Italy were enrolled. All patients underwent a complete ophthalmic examination, including 3-mm × 3-mm optical coherence tomography angiography centered on the macula. The vessel density was calculated in the three plexuses (i.e., SCP, DCP, and choriocapillaris) by mean of image binarization, and foveal avascular zone area was manually outlined at SCP and DCP with ImageJ software.In the SCP, patients with AOFVD disclosed a significant reduction of global (P < 0.001), parafoveal (P = 0.0017), and perifoveal (P = 0.0019) vessel density. In the DCP, parafoveal vessel density was higher in patients with AOFVD (P = 0.0026), whereas no significant difference was appreciated for both the global image (P = 0.5) and the perifoveal area (P = 0.5). Patients with AOFVD showed less dense choriocapillaris (P = 0.012) and perifoveal circle (P = 0.0152), whereas no difference was observed in the perifoveal zone (P = 0.07). Foveal avascular zone area was significantly enlarged at the DCP (P = 0.0184), but not at the SCP.Patients with AOFVD have quantitative vascular alterations in all vascular layers.