INTRODUCTION: Aflibercept 8 mg administered in extended dosing intervals has shown non-inferior visual gains and comparable safety profile to aflibercept 2 mg in the PULSAR pivotal randomized clinical trial and has the potential to reduce the treatment burden of treating neovascular age-related macular degeneration (nAMD). This study aimed at gathering robust evidence to assess the comparative efficacy, safety, and treatment burden of aflibercept 8 mg against other anti-vascular endothelial growth factor (VEGF) agents as ranibizumab, brolucizumab, faricimab, and bevacizumab in patients with nAMD. METHODS: A systematic literature review (SLR) was conducted, targeting clinical trials of anti-VEGF agents in patients with nAMD. The results of the SLR were included in a network meta-analysis (NMA) comparing aflibercept 8 mg to other anti-VEGF treatments in nAMD, considering a 1-year time horizon. Treatment efficacy was assessed based on the change in best-corrected visual acuity (BCVA) from baseline, the proportion of patients gaining or losing 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and changes in anatomical outcomes measured as change in central retinal thickness (CRT) or central subfield thickness (CST). Safety was assessed considering the incidence of ocular and non-ocular adverse events. Treatment burden was defined as the mean number of intravitreal injections over the study period. RESULTS: The base-case NMA involving 21 studies did not show significant differences between aflibercept 8 mg and comparators regarding BCVA change from baseline and proportion of patients with a gain or loss of ≥ 15 letters. On the anatomical endpoints, aflibercept 8 mg was associated with statistically significant improvement in CRT/CST change from baseline compared with ranibizumab in fixed and pro re nata regimens. No significant differences were identified versus the other anti-VEGF. The analysis of the safety outcomes did not identify any significant differences between aflibercept 8 mg and any of the comparators. During the first year of treatment, patients treated with aflibercept 8 mg (following 12- or 16-week injection intervals) received on average 5.9 and 5.1 injections, respectively. For the same period, patients treated with faricimab received from 6.2 to 6.7 injections, patients treated with ranibizumab from 7.62 to 12.14 injections, and patients treated with aflibercept 2 mg up to 7.67 injections. CONCLUSION: Aflibercept 8 mg demonstrates a comparable efficacy and safety to currently available anti-VEGF treatments for nAMD, with the potential added benefit of requiring fewer injections. These results suggest that aflibercept 8 mg could be a favourable treatment option for nAMD, achieving sustained disease control while alleviating the burden of injections on patients, caregivers, and healthcare providers.