Visual Acuity in a Large USH2A Cohort

Abstract

Purpose : To describe a large cohort of Usher syndrome (USH) and non-syndromic retinitis pigmentosa (RP) due to disease-causing variants in USH2A.

Methods : Patients with Usher syndrome or non-syndromic RP caused by pathogenic or likely pathogenic variants in USH2A were enrolled under protocols dedicated to study USH or RP and clinical data was collected prospectively between 2004 and 2019 in the Ophthalmic Genetics clinic of the National Eye Institute. Patients underwent ophthalmologic evaluations including visual acuity and field testing. Audiology was performed on patients with a diagnosis of USH. Molecular diagnosis was established through Sanger sequencing of USH genes or Next-Generation Sequencing.

Results : Sixty-seven patients with disease-causing variants in USH2A were enrolled, of which 49 (73.1%) had clinical diagnoses of USH and 18 (26.9%) non-syndromic RP. Forty-one (61.2%) were female, and 26 (38.8%) were male. Forty-six (68.7%) patients were followed longitudinally for a median of three visits and five years. The average age at last visit was 42.3 years (SD=15.6). At last visit, the average logMAR best corrected visual acuity in the better seeing eye was 0.38 (SD=0.66). Patients younger than 50 years of age (n=44) had an average logMAR of 0.15 in the better acuity eye and 0.25 in the worse acuity eye. Better eye logMAR was 0.53 for patients between 50 and 59 years of age (n=11) and 1.07 for patients older than 60 years. The most prevalent disease-causing variants were c.2299delG and p.C759F. Eleven (22.4%) patients with USH had one truncating variant and 29 (59.2%) had two. No patients with non-syndromic RP had two truncating variants.

Conclusions : Our cohort has a diverse profile of genetic variants in USH2A. Despite progressive visual field loss, note is made of relative visual acuity preservation at least through the fifth decade of life in this cohort of USH2A patients. This has implications for visual function prognostication and for planning of therapeutic clinical trials.

This is a 2020 ARVO Annual Meeting abstract.