The RUSH2A Study: Best-Corrected Visual Acuity, Full-Field Electroretinography Amplitudes, and Full-Field Stimulus Thresholds at Baseline.

Abstract

<h4>Purpose</h4>The purpose of this study was to evaluate baseline best corrected visual acuity (BCVA), full-field electroretinography (ERG), full-field stimulus thresholds (FST), and their relationship with baseline demographic and clinical characteristics in the Rate of Progression in Usher syndrome type 2 (<i>USH2A</i>)-related Retinal Degeneration (RUSH2A) multicenter study.<h4>Methods</h4>Participants had Usher syndrome type 2 (USH2, <i>N</i> = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP, <i>N</i> = 47) associated with biallelic variants in the <i>USH2A</i> gene. Associations of demographic and clinical characteristics with BCVA, ERG, and FST were assessed with regression models.<h4>Results</h4>In comparison to ARRP, USH2 had worse BCVA (median 79 vs. 82 letters; <i>P</i> < 0.001 adjusted for age), lower rod-mediated ERG b-wave amplitudes (median 0.0 vs. 6.6 µV; <i>P</i> < 0.001) and 30 Hz flicker cone-mediated ERG amplitudes (median 1.5 vs. 3.1 µV; <i>P</i> = 0.001), and higher (white, blue, and red) FST thresholds (means [-26, -31, -23 dB] vs. [-39, -45, -28 dB]; <i>P</i> < 0.001 for all stimuli). After adjusting for age, gender, and duration of vision loss, the difference in BCVA between diagnosis groups was attenuated (<i>P</i> = 0.09). Only diagnosis was associated with rod- and cone-mediated ERG parameters, whereas both genders (<i>P</i> = 0.04) and duration of visual loss (<i>P</i> < 0.001) also were associated with FST white stimulus.<h4>Conclusions</h4>USH2 participants had worse BCVA, ERG, and FST than ARRP participants. FST was strongly associated with duration of disease; it remains to be determined whether it will be a sensitive measure of progression.<h4>Translational relevance</h4>Using standardized research protocols in RUSH2A, measures have been identified to monitor disease progression and treatment response and differentiate features of prognostic relevance between USH2 and ARRP participants with <i>USH2A</i> mutations.