Choriocapillaris Flow Signal Impairment in Sorsby Fundus Dystrophy

Abstract: Purpose: To quantify choriocapillaris flow alterations in early Sorsby Fundus Dystrophy (SFD) and to investigate the relationship of choriocapillaris flow with the choroidal and outer retinal microstructure. Methods: In this prospective case-control study, 18 eyes of 11 patients with early SFD and 32 eyes of 32 controls without ocular pathology underwent multimodal imaging including spectral-domain optical coherence tomography (OCT)followed by deep-learning-based layer segmentation. OCT-angiography (OCT-A) was performed to quantify choriocapillaris flow signal deficits (FDs). Differences in choriocapillaris flow area percentage between SFD patients and controls were determined and a structure-function correlation with outer retinal layer thicknesses were analyzed based on mixed model analysis. Results: SFD patients exhibited a significantly greater choriocapillaris FDs area percentage than controls (estimate [95% CI] 32.05% [24.31-39.80] vs. 23.36% [20.64-26.09], P<0.001), even when adjusting for age. Choroidal thickness was a structural OCT surrogate of the choriocapillaris FD area percentage (-0.82% per 100 micrometer, P=0.017), whereas retinal-pigment-epithelium-drusen-complex thickness was not informative regarding choriocapillaris FDs (P=0.932). The choriocapillaris FD area percentage was associated with an altered microstructure of the overlying photoreceptors (outer-segments, inner-segments and outer-nuclear-layer thinning of -0.31, -0.12 and -0.47 $\mu$m per %FD, respectively, P<0.001). Conclusions: Patients with early SFD exhibit pronounced abnormalities of choriocapillaris flow signal on OCT-A, which are not limited to areas of sub-RPE deposits seen in OCT imaging. Thus, analysis of the choriocapillaris flow may enable clinical trials at earlier disease stages in SFD and possibly in mimicking diseases with an impaired Bruchs membrane including age-related macular degeneration.