Biomarkers in Usher syndrome: ultra-widefield fundus autofluorescence and optical coherence tomography findings and their correlation with visual acuity and electrophysiology findings

Purpose To investigate the functional and structural biomarkers and their correlation with Usher syndrome (USH). Methods Medical records, imaging and electrophysiology test results of USH patients attending the Save Sight Institute between 2012 and 2017 were reviewed. Best corrected visual acuity (BCVA), ultra-widefield autofluorescence (UW-FAF), spectral-domain optical coherence tomography (SD-OCT), full-field electroretinogram and pattern electroretinogram (pERG) were performed. SD-OCT scans assessed central macular thickness (CMT), greatest linear diameter of preserved outer retinal layers-macular island (MI) and presence of cystoid macular edema (CME). UW-FAF images were qualitatively graded to identify hypo/hyperfluorescence patterns in the peripheral fundus. Results Thirty-six eyes from 18 subjects were included. Mean BCVA was 0.22 +/- 0.3 LogMAR. MI extent was significantly associated with better vision (beta = - 0.175 per 1000 mu m; R-2 = 0.487; P = 0.002; Fig. 4). A higher pERG P50 was associated with a larger macular island (beta = 782 per mu V; R-2 = 0.238; P = 0.025), while a higher pERG N95 was associated with a smaller macular island (beta = - 499 per mu V; R-2 = 0.219; P = 0.030). Mean CMT was 271 +/- 35 mu m and was significantly associated with better vision (beta = - 0.083 per 10 mu m; R-2 = 0.612; P < 0.001). CME was diagnosed in 47.2% (n = 17) eyes. There was no significant difference in mean BCVA for those with CME (0.19 +/- 0.2 LogMAR) and without CME (0.40 +/- 0.5; R-2 = 0.081; P = 0.17). All patients had abnormal UW-FAF. Four main patterns of change were identified (granular 55%, annular 11%, bone spicule 17% and patchy 17%). Patients with the patchy pattern demonstrated worse BCVA in comparison with those with granular (P < 0.0001) and bone spicule (P = 0.0179) patterns. Conclusions Structural changes identified on OCT and UW-FAF correlated with BCVA and pERG in this cohort representing different stages of the disease. These parameters could represent reliable biomarkers in therapeutic clinical trials on USH.