Acquired vitelliform lesions (AVLs) are associated with a large spectrum of retinal diseases, among which is age-related macular degeneration (AMD). The purpose of this study was to characterize AVLs’ evolution in AMD patients using optical coherence tomography (OCT) technology and ImageJ software. We measured AVLs’ size and density and followed their impacts over surrounding retinal layers. Average retinal pigment epithelium (RPE) thickness in the central 1 mm quadrant (45.89 ± 27.84 µm vs. 15.57 ± 1.40 µm) was significantly increased, as opposed to the outer nuclear layer (ONL) thickness, which was decreased (77.94 ± 18.30 µm vs. 88.64 ± 7.65 µm) in the vitelliform group compared to the control group. We found a continuous external limiting membrane (ELM) in 55.5% of the eyes compared to a continuous ellipsoid zone (EZ) in 22.2% of the eyes in the vitelliform group. The difference between the mean AVLs’ volume at baseline compared to the last visit for the nine eyes with ophthalmologic follow-up was not statistically significant (p= 0.725). The median follow-up duration was 11 months (range 5–56 months). Seven eyes (43.75%) were treated with intravitreal anti-vascular endothelium growth factor (anti-VEGF) agent injections, in which we noted a 6.43 ± 9 letter decrease in the best-corrected visual acuity (BCVA). The increased RPE thickness could suggest hyperplasia contrary to the decreased ONL, which could mirror the impact of the vitelliform lesion on photoreceptors (PR). Eyes that received anti-VEGF injections did not show signs of improvement regarding BCVA.