Clinical Characteristics of Patients with Neovascular Age-Related Macular Degeneration and Responses to Anti-VEGF Therapy: Four-Group Stratification Based on Drusen and Punctate Hyperfluorescence

<b>Background/Objectives</b>: Different disease subtypes in neovascular age-related macular degeneration (nAMD) influence treatment burden, yet existing classifications such as the pachychoroid neovasculopathy (PNV)/non-PNV dichotomy may not fully capture clinical heterogeneity. This study aimed to compare the 12-month outcomes of intravitreal aflibercept (IVA) in treatment-naïve patients with unilateral nAMD stratified by the presence or absence of drusen and punctate hyperfluorescence (PH). <b>Methods</b>: This retrospective study included 130 eyes of 130 patients categorized into the Drusen-/PH-, Drusen+/PH-, Drusen-/PH+, and Drusen+/PH+ groups. Their best-corrected visual acuity, retinal thickness, choroidal thickness, number of injections, no-retinal fluid rate during the loading dose regimen, and 12-month retreatment rate following treatment initiation were determined. The primary outcome was 12-month retreatment rate for the four groups, which was determined using Kaplan-Meier curves and log-rank tests. Exploratory metric multidimensional scaling (MDS) was used to visualize the baseline profiles. <b>Results</b>: The 12-month retreatment rates of the groups were significantly different. The Drusen+/PH- group had a higher retreatment rate and required more injections than the Drusen-/PH+ and Drusen+/PH+ groups. The Drusen+/PH- group was older than the Drusen-/PH+ and Drusen-/PH- groups. The Drusen-/PH+ group had a thicker choroid than the Drusen+/PH- group. The MDS results clear separation of the groups, consistent with the older age of the Drusen+/PH- group and the thicker choroid of the Drusen-/PH+ group. <b>Conclusions</b>: nAMD stratified based on drusen and PH differed in age, choroidal thickness, and IVA outcomes. The four-category framework provides greater pathophysiologic and therapeutic resolution than the simple PNV/non-PNV dichotomy and may help anticipate injection demand to guide individualized dosing strategies.