PURPOSE. The purpose of this study was to examine retinal topographical differences between intermediate age-related macular degeneration (iAMD) with reticular pseudodrusen (RPD) versus iAMD without RPD, using high-density optical coherence tomography (OCT) cluster analysis. METHODS. Single eyes from 153 individuals (51 with iAMD+RPD, 51 with iAMD, and 51 healthy) were propensity-score matched by age, sex, and refraction. High-density OCT grid-wise (60 × 60 grids, each approximately 0.01 mm2 area) thicknesses were custom-extracted from macular cube scans, then compared between iAMD+RPD and iAMD eyes with correction for confounding factors. These “differences (μm)” were clustered and results de-convoluted to reveal mean difference (95% confidence interval [CI]) and topography of the inner retina (retinal nerve fiber, ganglion cell, inner plexiform, and inner nuclear layers) and outer retina (outer plexiform/Henle’s fiber/outer nuclear layers, inner and outer segments, and retinal pigment epithelium-to-Bruch’s membrane [RPE-BM]). Differences were also converted to Z-scores using normal data. RESULTS. In iAMD+RPD compared to iAMD eyes, the inner retina was thicker (up to +5.89 [95% CI = +2.44 to +9.35] μm, P < 0.0001 to 0.05), the outer para-central retina was thinner (up to −3.21 [95% CI = −5.39 to −1.03] μm, P < 0.01 to 0.001), and the RPE-BM was thicker (+3.38 [95% CI = +1.05 to +5.71] μm, P < 0.05). The majority of effect sizes (Z-scores) were large (−3.13 to +1.91). CONCLUSIONS. OCT retinal topography differed across all retinal layers between iAMD eyes with versus without RPD. Greater para-central photoreceptor thinning in RPD eyes was suggestive of more advanced degeneration, whereas the significance of inner retinal thickening was unclear. In the future, quantitative evaluation of photoreceptor thicknesses may help clinicians monitor the potential deleterious effects of RPD on retinal integrity.