Multicenter Natural History Study and Long-Term Cochlear Implant Outcomes in Usher Syndrome Subtypes

OBJECTIVES: Usher syndrome (USH) is an inherited disorder that causes bilateral sensorineural hearing loss (SNHL), retinitis pigmentosa, and vestibular defects. It represents the most common cause of combined deaf-blindness worldwide. Mutations in the nine known underlying genes are categorized into three types: USH type 1 has the earliest, most severe onset, while the much more common USH type 2 is comparatively mild with delayed onset and moderate symptoms. USH type 3 is very rare and exhibits variable clinical manifestations. The current standard of care for SNHL in USH is comprised of conventional hearing aids and/or cochlear implantation depending on the severity of symptoms. However, existing studies on treatment outcomes generally have rather short follow-up durations from a single institution and rarely distinguish between the individual USH subtypes. DESIGN: This retrospective multicenter cohort study analyzed 655 audiograms of 33 patients (66 ears) with genetically confirmed USH. Patient-specific characteristics and treatments were correlated with pure-tone average thresholds and speech perception performance over a mean (SD) of 7 yrs and 10 mo (9 yrs and 11 mo) overall and 8 yrs and 2 mo (6 yrs and 3 mo) after cochlear implantation. RESULTS: Conventional hearing aids improved thresholds on average (SD) by 20.1 (10.9) dB HL regardless of age, but aided hearing still deteriorated concurrently with the natural progression of SNHL. In patients with severe-to-profound SNHL or complete deafness, cochlear implantation rescued hearing to average thresholds of 37.9 (7.0) dB HL 1 yr post-implantation, 37.3 (10.3) dB HL after 2 years, and 27.5 (7.1) dB HL after 15 to 20 yrs. Every single patient who received an implant benefited from it, irrespective of the age at implantation or the causative USH mutation. CONCLUSIONS: With new gene therapies for USH in development, the findings reported here can serve as a benchmark for the comparison of novel treatments with the current clinical standard of care around the world. Larger-scale studies with more consistent monitoring of hearing and speech perception ability, as well as more extensive genetic testing, could further elucidate the benefits of current treatments for different (sub-)types of USH.