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The purpose of this study was to evaluate the functional relevance of longitudinal changes in hyperautofluorescent areas and flecks in Stargardt disease (STGD1) using short-wavelength autofluorescence (SW-AF) imaging. In this prospective, longitudinal study, 31 patients with STGD1 (56 eyes) underwent microperimetry (MP) and SW-AF imaging twice in 3 to 5 years. A total of 760 MP test points were included in the statistical analysis based on stable fixation and accurate alignment of SW-AF and MP. Autofluorescence intensity was qualitatively assessed in all MP test points. Small circumscriptive hyperautofluorescent lesions were defined as flecks. Longitudinal imaging characteristics observed on SW-AF were classified into the following categories: appearing, disappearing, and stable flecks, stable hyperautofluorescent, and stable background autofluorescence. The relationship between SW-AF intensity changes and MP changes was analyzed using a linear mixed model corrected for baseline sensitivity. Retinal sensitivity declined most in locations without change in SW-AF intensity. Functional decline per year was significantly larger in flecks that disappeared (-0.72 ± 1.30 dB) compared to flecks that appeared (-0.34 ± 0.65 dB), if baseline sensitivity was high (≥10 dB; P < 0.01). The correlation between the change observed on SW-AF and the sensitivity change significantly depended on the sensitivity at baseline (P = 0.000). Qualitative longitudinal assessment of SW-AF poorly reflected the retinal sensitivity loss observed over the course of 3 to 5 years. When aiming to assess treatment effect on lesion level, a multimodal end point including MP focused on hyperautofluorescent lesions appears essential but needs further studies on optimizing MP grids, eye-tracking systems, and alignment software.


Patty P A Dhooge, Esmee H Runhart, Stanley Lambertus, Nathalie M Bax, Johannes M M Groenewoud, B Jeroen Klevering, Carel B Hoyng. Correlation of Morphology and Function of Flecks Using Short-Wave Fundus Autofluorescence and Microperimetry in Patients With Stargardt Disease. Translational vision science & technology. 2021 Mar 01;10(3):18

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PMID: 34003952

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