Backgrounds and Objectives: To analyze the influence of multiple anti-VEGF intravitreal injections for exudative age-related macular degeneration on the thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GC + IPL) using spectral domain optical coherence tomography (SD-OCT). Materials and Methods: A prospective interventional study of consecutive patients treated with intravitreal bevacizumab (IVB) was performed. Average and sectorial values of RNFL and GC + IPL thickness were recorded using Cirrus SD-OCT at 0, 6, 12, and 24 months. Patients suffering from any ocular disease that could affect RNFL or GC + IPL thickness were excluded. Results: A total of 135 patients (70 women and 65 men, aged 65 ± 15 years) were included. The average number of injections per patient was 12.4 ± 2.4. Average RNFL and GC + IPL thickness prior to the first injection (87.6 ± 12.2 and 47.2 ± 15.5 respectively), and after 24-month follow-up (86.2 ± 12.6 and 46.7 ± 11.9 respectively) did not differ significantly (p > 0.05). There was a significant decrease in GC2, GC5 segments, and minimum GC + IPL thickness. Conclusion: Repeated anti-VEGF treatment did not cause significant changes in the thickness of RNFL and GC + IPL layers over a period of 24 months. The detected decrease in GC2 and GC5 sectors, as well as in minimum GC + IPL thickness, could be a sign of ganglion cell damage induced by the treatment or could occur during the natural course of the disease.