Multimodal Adaptive Optics Imaging of the Cellular Status and Progression of the Outer Retinal Complex in Bietti Crystalline Dystrophy

Abstract

Purpose : To evaluate and longitudinally follow the cellular status of the outer retinal complex (photoreceptor, retinal pigment epithelial cells (RPE), and choriocapillaris (CC)) in Bietti Crystalline Dystrophy (BCD) using multimodal adaptive optics (AO) imaging.

Methods : Four eyes from two unrelated patients (P1: 52, P2: 43 years old) with molecularly-confirmed mutations in the CYP4V2 gene and clinical phenotypes consistent with BCD were imaged using high resolution imaging including color fundus photography, spectral-domain (SD) optical coherence tomography (OCT), and a custom-built multimodal AO imager incorporating AO-SDOCT and indocyanine green (ICG) imaging capabilities (Comm Biol 1:189,2018) to reveal the cone photoreceptors, RPE cells, and CC.

Results : Discrete crystals found in non-atrophic macular areas of the retina were mostly localized in the outer retina near the RPE layer (SDOCT and AO-SDOCT). Near the fovea, contiguous mosaics of intact cone photoreceptors were observed above enlarged RPE and intact CC, including above crystals. In patient P1 (advanced BCD), quantitative morphological measurements of cones, RPE, and CC were significantly different from normal (p<0.05) with the greatest degree of change observed in the RPE and CC. Intact CC was observed with an abrupt loss at the edge of atrophy. In patient P2 (early BCD), cone spacing and CC flow voids were within or near normal limits, but RPE cells were significantly enlarged (Table 1). Follow-up imaging performed 7 months afterwards revealed a highly dynamic process of disappearance of old crystals and formation of new crystals with a dramatic redistribution of RPE cell fluorescence that mirrored the redistribution of crystals. Interestingly, RPE cells associated with crystals were largely hypofluorescent on late phase AO-ICG imaging. Despite the rapid reconfiguration of crystals and RPE, there was no difference in cone spacing attributed to the loss of a crystal (p=0.7, paired two-tailed t-test, n=10 pairs of regions containing a single crystal in visit 1 with no crystal in visit 2). Longitudinal assessment of the CC showed relative preservation of flow voids despite the overlying changes in the RPE.

Conclusions : Our data suggests that the RPE (and crystals associated with RPE) undergoes dramatic remodeling early in BCD, with photoreceptor and CC degeneration occurring as secondary events.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.