ObjectiveTo compare the visibility and accessibility of the outer retina in neovascular age-related macular degeneration (nAMD) between 2 OCT devices. MethodsIn this prospective, cross-sectional exploratory study, differences in thickness and loss of individual outer retinal layers in eyes with nAMD and in age-matched healthy eyes between a next-level High-Res OCT device and the conventional SPECTRALIS OCT (both Heidelberg Engineering GmbH, Heidelberg, Germany) were analyzed. Eyes with nAMD and at least 250 nL of retinal fluid, quantified by an approved deep-learning algorithm (Fluid Monitor, RetInSight, Vienna, Austria), fulfilled the inclusion criteria. The outer retinal layers were segmented using automated layer segmentation and were corrected manually. Layer loss and thickness were compared between both devices using a linear mixed-effects model and a paired t test. ResultsNineteen eyes of 17 patients with active nAMD and 17 healthy eyes were included. For nAMD eyes, the thickness of the retinal pigment epithelium (RPE) differed significantly between the devices (25.42 μm [95% CI, 14.24–36.61] and 27.31 μm [95% CI, 16.12–38.50] for high-resolution OCT and conventional OCT, respectively; p = 0.033). Furthermore, a significant difference was found in the mean relative external limiting membrane loss (p = 0.021). However, the thickness of photoreceptors, RPE integrity loss, and photoreceptor integrity loss did not differ significantly between devices in the central 3 mm. In healthy eyes, a significant difference in both RPE and photoreceptor thickness between devices was shown (p < 0.001). ConclusionCentral RPE thickness was significantly thinner on high-resolution OCT compared with conventional OCT images explained by superior optical separation of the RPE and Bruch's membrane.