Purpose:The administration frequency of intravitreal anti-vascular endothelial growth factor (anti-VEGF) in neovascular age-related macular degeneration (AMD) have been widely discussed. The primary objective of the study was to explore the association between anatomical outcomes and changes in functional outcome. Methods:This was a retrospective cohort study of patients with newly diagnosed neovascular AMD with a minimum of 12 months of follow-up. Only one eye per patient was included. Patients were treated according to the observe-and-plan or the pro-re-nata regimen. All patients were regularly examined from the time of diagnosis up to 24 months. The effect of intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelium detachment (PED) at any time point on visual acuity (VA) was tested, as well as the long-term effect and the risk of losing VA.Further, the variability of central retinal thickness (CRT) was calculated for each eyes' individual measures during the observation period, excluding the monthly loading phase. The prognostic effect of each factor on VA was estimated by regression analysis. The primary outcome measure was VA, which was correlated with the presence or absence of fluid, seen as IRF, SRF or PED.Results: A total of 504 treatment naïve eyes from 504 patients was included. The presence of IRF was associated with lower VA at all visits (p < 0.001). However, the presence of SRF or PED was not significantly associated with worse VA at any time point during the observation period. Patients in the upper quartile of CRT variance had a greater loss in VA after 12 and 24 months (p < 0.001). Conclusions:In this retrospective cohort study, the presence of intraretinal fluid was associated with poorer visual outcome in neovascular AMD patients treated with anti-VEGF, but the presence of subretinal fluid and PEDs was not. This suggests that IRF is worse than subretinal fluid and PEDs for AMD outcomes and therefore requires the most intensive treatment. Further, we found that patients with the highest CRT variability during the study period had poorer visual outcomes after 12 and 24 months, indicating that stringent control of retinal fluid volume fluctuations is important to prevent visual acuity decline over time.