AIM: To investigate thickness characteristics and vascular plexuses in retinas with reticular pseudodrusen (RPD) as an early detection strategy for age-related macular degeneration (AMD). METHODS: This retrospective study included 24 subjects (33 eyes) with RPD and 25 heathy control subjects (34 eyes). The superficial capillary plexus (SCP) and the deep capillary plexus (DCP) of the retinal posterior poles were investigated with optical coherence tomography angiography (OCTA). Retinal thicknesses and vessel densities were analyzed statistically. RESULTS: The general retinal thicknesses of RPD eyes were significantly decreased (95%CI -14.080, -0.655; P=0.032). The vessel densities of DCP in RPD eyes were significantly increased in the global (95%CI 1.067, 7.312; P=0.027), parafoveal (95%CI 0.417, 5.241; P=0.022), and perifoveal (95%CI 0.181, 6.842; P=0.039) quadrants. However, the vessel densities of the SCP were rarely increased in the eyes with RPD. CONCLUSION: The thinning of retinas in the RPD group suggests a reduction in the number of cells. Additionally, the increased vessel density of the DCP in retinas with RPD indicates a greater demand for blood supply, possibly due to the hypoxia induced RPD compensation caused by RPD in the outer retina. This study highlights the pathological risks associated with RPD and emphasizes the importance of early intervention to retard the progression of AMD.