Distinct Pathogenic Mechanisms of Neurodegeneration in Pachychoroid Pigment Epitheliopathy Versus Intermediate Age-Related Macular Degeneration

To investigate distinct neurodegeneration mechanisms in pachychoroid pigment epitheliopathy (PPE) versus age-related macular degeneration (AMD) using quantitative optical coherence tomography (OCT) with age-matched controls. This cross-sectional study of 184 subjects included 50 age-matched controls (25 young: 47–63 years; 25 elderly: 67–83 years), 57 PPE patients (47–63 years), 39 AMD drusen patients (64–80 years), and 38 AMD reticular pseudodrusen patients (67–83 years). Primary outcomes included ganglion cell layer–inner plexiform layer (GCL-IPL) thickness, subfoveal choroidal thickness, and choroidal volume using swept-source OCT. All pathologic conditions showed significant neurodegeneration versus age-matched controls (p < 0.001). PPE demonstrated choroidal thickening (410.5 ± 32.9 μm vs. 306.0 ± 10.8 μm controls) with inverse choroidal–neural correlations (r = −0.52 to −0.61, p < 0.001). AMD variants showed choroidal thinning (187–238 μm vs. 277 μm elderly controls) with positive correlations (drusen: r = +0.43, p = 0.006; RPD: r = +0.68, p < 0.001). Two distinct pathways cause neurodegeneration: compressive (PPE: choroidal thickening → choriocapillaris compression → neurodegeneration) and ischemic (AMD: choroidal thinning → hypoperfusion → neurodegeneration).