Enlarged retinal pigment epithelial cells observed in Stargardt disease assessed by adaptive optics enhanced indocyanine green ophthalmoscopy

Abstract

Purpose : To characterize retinal pigment epithelial (RPE) cells in Stargardt disease (STGD1) using adaptive optics enhanced indocyanine green (AO-ICG) (IOVS 57:4376-4384, 2016).

Methods : Four patients with Stargardt disease and confirmed pathogenic variants in ABCA4 were recruited for this study. Participants had preserved foveal structure, visual acuity 20/25 or better and varying disease severity. Following injection of indocyanine green (ICG) dye, both eyes of each patient were imaged in the late phase using a custom-built AO-ICG instrument to assess RPE cells labeled by ICG dye in the context of multimodal clinical imaging. RPE cell-to-cell spacing was quantified across the macula in areas with intact RPE as assessed by fundus autofluorescence and spectral domain optical coherence tomography imaging, including at the fovea, adjacent to fovea, and in some eyes, near atrophy.

Results : Overall, AO-ICG revealed a heterogeneous distribution of RPE cell size across the macula. RPE cells could not be successfully imaged beneath flecks due to presumed blocking of the late phase AO-ICG signal by the flecks. Across all eyes, in the fovea, RPE cells exhibited the characteristic heterogeneous AO-ICG pattern but with increased average spacing (23.2±3.3 µm, N=8 locations, ~65% above normal). In the 2 eyes without frank atrophy, there was a region surrounding the fovea in which RPE cells were irregularly enlarged (spacing: 40.7±9.8 µm, N=6). In contrast, in the 6 eyes with frank atrophy, enlarged RPE cells with increased spacing (52.9±12.5 µm, N=18) were observed near the atrophy. Interestingly, in the eyes with earlier stages of the disease (mild, juxtafoveal atrophy or no atrophy), the RPE cells were less affected in the perifoveal regions (26.0±1.9 µm, N=6 in eyes without atrophy; 23.3±2.0 µm, N=8 in eyes with the initial stages of juxtafoveal atrophy). In contrast, in the 4 eyes which were at a more advanced stage (large central area of atrophy with foveal sparing), the RPE was disrupted (58.9±9.5 µm, N=12) in the perifovea.
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Conclusions : Enlargement of RPE cells were observed in all eyes with STGD1, especially in the proximity of atrophy. The spatial extent of enlarged RPE may depend on the severity of the disease. Monitoring RPE cell spacing may be an important parameter for evaluating eyes with STGD1.

This is a 2020 ARVO Annual Meeting abstract.