To quantitatively compare the spectral-domain optical coherence tomography (SD-OCT) characteristics of inner and outer intraretinal hyperreflective foci (IHRF) in eyes with age-related macular degeneration (AMD) and to investigate their potential pathophysiological implications.

This retrospective study included 64 eyes from 64 treatment-naive AMD patients. SD-OCT imaging (Spectralis, Heidelberg Engineering) was performed using a 20° × 20° macular scan centered on the fovea. Inner IHRF were defined as lesions located above the inner border of the inner nuclear layer, while outer IHRF were situated below the inner border of outer nuclear layer. Semi-automated segmentation and quantitative analysis of IHRF were performed using ImageJ. Parameters analyzed included mean area, normalized mean reflectivity, greatest linear dimension (GLD), and mean circularity.

A total of 32 eyes with 68 inner IHRF and 32 eyes with 113 outer IHRF were included. The mean area of inner and outer IHRF was 887.09 ± 942.63 μm2 and 832.27 ± 881.75 μm2, respectively (p = 0.69). Normalized reflectivity was 1.18 ± 0.14 for inner IHRF versus 1.20 ± 0.17 for outer IHRF (p = 0.54), and circularity was 0.81 ± 0.19 for inner IHRF versus 0.79 ± 0.20 for outer IHRF (p = 0.71). The mean GLD measured 42.8 ± 35.2 μm for inner IHRF and 45.3 ± 30.4 μm for outer IHRF (mean difference: 2.5 μm, 95 % CI: 7.57 to 12.57; p = 0.595). No statistically significant differences were observed between inner and outer IHRF in any evaluated parameters.

Inner and outer IHRF in AMD share similar quantitative SD-OCT characteristics, suggesting common pathological mechanisms irrespective of retinal location. These findings challenge the notion of distinct cellular origins and highlight the need for further research.