The aim of this study was to evaluate the long-term effect of intravitreal ranibizumab on the retinal nerve fiber layer (RNFL) in exudative age-related macular degeneration (AMD). Patients with treatment naive neovascular AMD in one eye were enrolled into the study. Following 3 monthly intravitreal ranibizumab injections, the patients were evaluated according to disease activity and re-injections were performed according to "treat and extend" protocol. During the follow-up, peripapillary nerve fiber layer thickness measurements were compared with normal fellow eyes. Forty-four eyes of 11 women and 11 men with the mean age of 66.3 ± 8.8 years (50-80) were enrolled into the study. All patients had completed at least 12 months of follow-up time. Patients received an average of 4.7 (3-11 injections) intravitreal injections. At baseline, no significant difference was observed between two groups for RNFL thickness, which was assessed as quadrants (p = 0.250-0.944) and globally (p = 0.814). In each group, there was a significant RNFL thinning (p = 0.009 and 0.022) after the third month, whereas no significant difference was observed between treated and untreated eyes. Patients were also classified according to the number of injections, and RNFL thickness showed no difference between eyes treated with less or more than five intravitreal injections (p = 0.757-0.973). Although there was no statistically significant difference in RNFL thickness between study and control eyes during 12 months of follow-up, a significant thinning was recorded in both groups compared with baseline values. Cross-sectional images with higher resolutions and precise segmentation opportunities are needed to investigate the hypothesis "VEGF neutralization and inhibition of cell maintenance" in detail.