Macular degeneration (MD) affects central vision and represents the leading cause of visual diseases in elderly population worldwide. As a consequence of central vision loss, MD patients develop a preferred retinal locus (PRL), an eccentric fixation point that replaces the fovea. Here, our aim was to determine whether and to what extent spontaneous plasticity takes place in the cortical regions formerly responding to central vision and whether a visual training based on perceptual learning (PL) can boost this plasticity within the PRL area. Spontaneous and PL-induced cortical plasticity were characterized by using lateral masking, a contrast sensitivity modulation induced by collinear flankers. This configuration is known to be sensitive to neural plasticity and underlies several rehabilitation trainings. Results in a group of 4 MD patients showed that collinear facilitation was similar to what observed in age- and eccentricity-matched controls. However, MD patients exhibited significantly reduced collinear inhibition, a sign of neural plasticity, consistent with the hypothesis of partial cortical reorganization. Three AMD patients from the same group showed a further reduction of inhibition after training, but not controls. This result suggests that PL might further boost neural plasticity, opening promising perspectives for the development of rehabilitation protocols for MD patients.