In this study the authors aim to evaluate the role of various factors for the development of retinal pigment epithelium (RPE) atrophy over a period of five years in patients with nAMD. Fifty-two newly diagnosed nAMD patients with complete absence of RPE atrophy prior to anti-VEGF treatment initiation were analysed using spectral domain optical coherence tomography (SD-OCT) for a mean follow-up time of 5.34±1.35 (± standard deviation) years. All patients had at least three years of follow-up. The total number of injections received from baseline until the last available examination was on average 24.46±9.96 with an average of 4.68±1.64 injections per year. Fourteen patients (29.6%) received only ranibizumab during the entire course of the study, whereas 38 patients (73.1%) were treated with various agents (ranibizumab and / or aflibercept and / or bevacizumab). Mean central retinal thickness (CRT) at baseline was 427.31±165.13µm. After six months, 11 of 52 patients (21.2%) developed RPE atrophy. The percentage of patients with newly developed RPE atrophy increased gradually to 28.8% after the first year, 40.4% at the second year, 44.2% at the third year, and 57.7% at the final visit after the third year. There was no statistical difference in the onset of RPE atrophy between patients who received a single-medication therapy with ranibizumab and those who switched medications (p=0.559). Atrophy onset was significantly associated with the duration of nAMD (mean 5.34 years; odds ratio = 1.83, p=0.012). Anti-VEGF injection number, age, C3d/C3 ratio, baseline intraocular VEGF, or delay to the first treatment had no influence on RPE atrophy. RPE atrophy has been suggested to occur as a result of choroidal neovascularisation (CNV)-associated mechanic, ischaemic, and inflammatory effects. Hence, it could be speculated that atrophy appears as a result of long-lasting disease effects and persisting local inflammation, independent of anti-VEGF therapy. Onset of macular atrophy (MA) seems to be an event that is not addressed by current anti-VEGF therapy and might additionally limit the long-term outcome of patients with nAMD. Limitations: Small sample size, a large range of follow-up time (3.13-7.26 years). The possibility of underlying RPE atrophy cannot be excluded in the cases with haemorrhage or exudates. Fundus fluorescein angiography (FFA) was not regularly available in the clinical follow-up, and hence, lack of measurements of atrophy size.