Degeneration of Melanin-Containing Structures Observed Longitudinally in the Eyes of SOD1(−/−) Mice Using Intensity, Polarization, and Spectroscopic OCT

PURPOSE: Melanin plays an important function in maintaining eye health, however there are few metrics that can be used to study retinal melanin content in vivo. METHODS: The slope of the spectral coefficient of variation (SSCoV) is a novel biomarker that measures chromophore concentration by analyzing the local divergence of spectral intensities using optical coherence tomography (OCT). This metric was validated in a phantom and applied in a longitudinal study of superoxide dismutase 1 knockout (SOD1(−/−)) mice, a model for wet and dry age-related macular degeneration. We also examined a new feature of interest in standard OCT image data, the ratio of maximum intensity in the retinal pigment epithelium to that of the choroid (RC ratio). These new biomarkers were supported by polarization-sensitive OCT and histological analysis. RESULTS: SSCoV correlated well with depolarization metrics both in phantom and in vivo with both metrics decreasing more rapidly in SOD1(−/−) mice with age (P < 0.05). This finding is correlated with reduced melanin pigmentation in the choroid over time. The RC ratio clearly differentiated the SOD1(−/−) and control groups (P < 0.0005) irrespective of time and may indicate lower retinal pigment epithelium melanin in the SOD1(−/−) mice. Histological analysis showed decreased melanin content and potential differences in melanin granule shape in SOD1(−/−) mice. CONCLUSIONS: SSCoV and RC ratio biomarkers provided insights into the changes of retinal melanin in the SOD1(−/−) model longitudinally and noninvasively. TRANSLATIONAL RELEVANCE: These biomarkers were designed with the potential for rapid adoption by existing clinical OCT systems without requiring new hardware.