A Natural History Study of Visual Function in Patients with Usher Syndrome Type 1C.

Abstract

Purpose : Usher syndrome (Usher) is the most common cause of concurrent hearing and vision impairment. There is considerable genetic and clinical heterogeneity with 15 causal genes and three clinic subtypes associated with Usher. Type 1 Usher (USH1), the most severe form, is characterized by deafness and vestibular areflexia at birth, and adolescent-onset retinitis pigmentosa (RP). Mutations in the USH1C gene account for approximately 6-8% of USH1 cases, however, the USH1C c.216G>A mutation (Acadian mutation) is responsible for nearly all USH1 cases in the Acadian population in Louisiana, USA and Canada. Despite having identified mutations responsible for Usher, a genotype-phenotype correlation has not been studied. We hypothesize that an early molecular diagnosis and better understanding of the natural clinical history of Usher will help determine the prognosis, management and rehabilitation options, and inform the design for clinical trials. We aim to characterize the deafness, vestibular areflexia and RP in Acadian USH1C patients.

Methods : Hearing, balance and visual function, including visual acuity (VA), and visual fields (VF), will be evaluated by retrospective chart review. Recruitment of patients will occur through multiple means, including blind-deaf support groups, community physicians, and Usher Syndrome symposiums throughout Louisiana. We will assess VA and VF over time and measure slopes of decline functions.

Results : 79 participants are currently enrolled, including 60 with USH1, ranging in age from 3 to 90 years. 88.4% (53/60) of USH1 cases have Acadian USH1C, 3.3% (2/60) have non-Acadian USH1C, and 8.3% (5/60) have not received genetic testing. Preliminary visual acuity (VA) and visual field (VF) data suggest that these visual indices decline in USH1C patients over time. VA data suggests a relative stability until age 40 and then rapid decline, while VF data suggest a more constant decline from 3 – 60 years.

Conclusions : A careful understanding of the natural progression of USH1C will provide clinical endpoints and improve care for patients. Clinical trials are planned based on these endpoints and natural history studies.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.