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

Year: 2025

Type: article

Abstract: INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Two distinct pathways cause neurodegeneration: compressive (PPE: choroidal thickening → choriocapillaris compression → neurodegeneration) and ischemic (AMD: choroidal thinning → hypoperfusion → neurodegeneration).

Source: Ophthalmology and Therapy

DOI: 10.1007/s40123-025-01246-4