Cellular-Level Characterization of Cone Photoreceptors and Retinal Pigment Epithelium in Stargardt Disease with Adaptive Optics Imaging

Structured Abstract Purpose The purpose of this study was to simultaneously visualize cone photoreceptors (cone) and retinal pigment epithelium (RPE) cells at the cellular level in Stargardt disease (STGD) using adaptive optics imaging. In addition, the feasibility of quantitative analysis was explored. Design Observational case series. Subjects Patients with STGD. Method Cone and RPE cells were simultaneously imaged at the cellular level using adaptive optics flood-illumination ophthalmoscopy (AO-FIO) and AO-transscleral flood illumination (AO-TFI). Quantitative metrics were derived and normalized as Z-scores to provide an exploratory assessment of the feasibility of cellular-level quantification. Main Outcome Measures Cellular-level cone and RPE integrity and abnormalities assessed by simultaneous AO-FIO and AO-TFI imaging. Results Using AO-FIO and AO-TFI, cone and RPE cells could be simultaneously visualized in eyes with STGD. In a subset of cases, cellular-level quantitative analysis was feasible. Imaging findings varied across patients and retinal regions, showing heterogeneous degrees of structural alteration in cone and RPE cells. In the quantitatively analyzed cases, cone density Z-scores showed marked reductions, with the lowest values of –3.28 in Case 1 and –2.90 in Case 2, whereas RPE cell density Z-scores showed only mild deviations and remained within the reference range in the analyzed regions. Conclusions AO-FIO and AO-TFI enable simultaneous cellular-level visualization of cone and RPE cells in STGD. This study characterized cellular-level structural features in STGD and demonstrated the feasibility of quantitative analysis in a subset of cases. These findings could contribute to a deeper understanding of STGD pathology and support future investigations aimed at treatment optimization.