Patient-reported visual functioning in persons with bi-allelic USH2A variants

Abstract

Purpose : To describe a patient-reported visual functioning outcome (PRO) at baseline in RUSH2A participants and explore relationships between PRO, visual acuity (VA) and hill of vision (V_TOT).

Methods : The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) is a multicenter, international, longitudinal natural history study of individuals with biallelic disease-causing variants in USH2A. History of hearing loss and baseline audiology exams were used to assign a clinical diagnosis of Usher syndrome type 2 (USH2) or autosomal recessive non-syndromic retinitis pigmentosa (ARRP). The VALVVFQ-48 was administered verbally in the local language of participants ≥18 years. ETDRS VA was measured in both eyes. V_TOT was determined from full-field static perimetry in the study eye (better VA). Baseline PRO measure was calculated using the method of successive dichotomizations, a type of Rasch analysis.

Results : Median age of the 120 participants at enrollment was 41 years (range: 19 to 80); 65 (54%) were female. Clinical diagnosis was USH2 in 75 participants and ARRP in 45. Median age of onset was 16 years [IQR: 13-22] in USH2 and 32 [IQR: 20-41] in ARRP, and median duration of disease was 17 [IQR: 10-27] and 13 years [IQR: 6.8-18], respectively. Median VA was 80 letters (interquartile range (IQR): 75, 85) in the study eye and 75 letters (IQR: 69, 82) in the fellow eye, and median V_TOT in the study eye was 20 dB-sr (IQR: 5.4 – 45). A wide range of PROs was seen with person measures ranging from -2.0 to 7.4 logits (median (IQR): 2.9 (1.5-3.8)). ARRP participants had similar PRO to USH2, both before (mean (95% CI): 2.8 (2.3-3.4) and 2.7 (2.3-3.2), respectively), and after adjusting for baseline differences in age, VA, duration of VA loss, and V_TOT [mean (95% CI): 2.5 (2.1-3.0) and 2.9 (2.6-3.3), respectively; p=0.25]. VA and V_TOT, separately, accounted for 29% and 26% of variation in PRO, respectively; (p<0.001 for each). Together, they accounted for 36% of variation in PRO.

Conclusions : Bi-allelic USH2A variants are associated with a large range of PRO using VALVVFQ-48. PRO in AARP and in USH2 were similar, despite concomitant hearing loss in USH2. VA and V_TOT appear to be significant and approximately equal contributors to PRO in this population. However, these 2 measures account for less than ½ of variation in PRO.

This is a 2021 ARVO Annual Meeting abstract.