This study investigated the pathophysiological features of pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD) by analysing and comparing cytokine profiles in aqueous humour (AH) collected from 18 PNV, 18 nAMD and 11 control patients. Responses to intravitreal injection of aflibercept were also analysed in the PNV and nAMD groups. In the PNV group, vascular endothelial growth factor (VEGF)-A was significantly lower than in the nAMD group (p = 0.03) but was almost identical to that in the control group (p = 0.86). The nAMD group showed positive correlations between interleukin (IL)-6 and IL-8 (r = 0.78, p < 0.001), IL-6 and monocyte chemoattractant protein (MCP)-1 (r = 0.68, p = 0.002) and IL-8 and MCP-1 (r = 0.68, p = 0.002). In the nAMD group, eyes with dry maculae one month after the first aflibercept injection showed significantly lower VEGF-A and placental growth factor (PlGF) at baseline than those with wet maculae (p = 0.02 for both). However, there was no significant difference between dry and wet maculae in the PNV group. The results suggest that angiogenic factors and proinflammatory cytokines may play the distinct roles in the pathogenesis of PNV and nAMD.