To assess the effects of intravitreal ranibizumab therapy on intraocular pressure (IOP) and retinal nerve fiber (RNFL) thickness. Forty-nine eyes of 49 patients with neovascular age-related macular degeneration (AMD) treated with intravitreal ranibizumab injections and 27 fellow eyes not requiring treatment were followed for 1 year. RNFL thickness, as measured by Fourier domain optical coherence tomography, and IOP were determined pre- and postinjection. After 12 months, the mean number of injections received was 4.8 ± 1.6. The incidence of IOP elevations (>5 mm Hg over baseline) observed at the time of injection was 0.4%. Baseline RNFL thickness was 105.7 ± 12.2 μm in the treatment group compared with 101.8 ± 11.6 μm in the control group (P = 0.176). At the end of follow-up, significant RNFL thinning was noted in the treatment group (100.2 ± 11.0 μm, P < 0.001), whereas no differences were found in the control group (100.5 ± 10.8 μm, P = 0.477). Intravitreal ranibizumab injections used to treat AMD caused a significant change in RNFL thickness after 12 months of follow-up.