Disease Course in Patients with Autosomal Recessive Retinitis Pigmentosa due to theUSH2AGene

Abstract

Purpose To estimate the mean rates of ocular function loss in patients with autosomal recessive retinitis pigmentosa due to USH2A mutations. Methods In 125 patients with USH2A mutations, we used longitudinal regression to estimate mean rates of change of Snellen visual acuity, Goldmann visual field area (V4e white test light), and 30 Hz (cone) full-field electroretinogram amplitude. We compared these rates to those of previously studied cohorts with dominant retinitis pigmentosa due to RHO mutations and with X-linked retinitis pigmentosa due to RPGR mutations. We also compared rates of change in patients with the Cys759Phe mutation, the USH2A mutation associated with nonsyndromic disease, with rates of change in patients with the Glu767fs mutation, the most common USH2A mutation associated with Usher syndrome, type II (i.e., retinitis pigmentosa and hearing loss). Results Mean annual exponential rates of decline for the USH2A patients were 2.6% for visual acuity, 7.0% for visual field area, and 13.2% for electroretinogram amplitude. The rate of acuity loss fell between the corresponding rates for the RHO and RPGR patients, while the rates for field and ERG amplitude loss were faster than those for the RHO and RPGR patients. No significant differences were found for patients with the Cys759Phe mutation versus patients with the Glu767fs mutation. Conclusions On average, USH2A patients lose visual acuity faster than RHO patients and slower than RPGR patients. USH2A patients lose visual field and cone electroretinogram amplitude faster than RHO patients and RPGR patients. Patients with a nonsyndromic USH2A mutation have the same retinal disease course as patients with syndromic USH2A disease.

Central Retina Functional Damage in Usher Syndrome Type 2: 22 Years of Focal Macular ERG Analysis in a Patient Population From Central and Southern Italy

“…This is in line with previous studies on RP patient cohorts, showing a 2% to 3% average annual rate of decline, once BCVA begins to decrease. 33,36,37 The finding that fERG losses precede BCVA decline by many years in USH2 patients is in accordance with a previous study on cone-rod dystrophies where we found that BCVA loss invariably followed fERG loss, with a variable delay of years. 24 We can only speculate as to why fERG is more sensitive than BCVA to central cone deficits.…”

“…[14][15][16]31,36,43 Conversely, fERG decline does not seem to depend on disease onset, but rather it follows an almost stereotyped course with age. It can still be used to estimate the average rate of central cone function decay, 23 but its restricted and almost invariant age window of decline makes it most of all a hallmark of the disease.…”

“…Indeed, whereas the onset of BCVA and Goldmann field decay varies from patient to patient, 14,15,36 fERG decline occurs in a restricted age window, with 75% of the loss occurring by 25 years of age in all patients.…”

Usher Syndrome: Genes, Proteins, Models, Molecular Mechanisms, and Therapies

“…. Additionally, although retinitis pigmentosa in USH is characterized to have an onset before www.intechopen.com Usher Syndrome: Genes, Proteins, Models, Molecular Mechanisms, and Therapies 299 or during puberty (Smith et al, 1994;Petit, 2001), more and more atypical USH patients have been found (Edwards et al, 1998;Sadeghi et al, 2006;Cohen et al, 2007;Fishman et al, 2007;Sandberg et al, 2008;Malm et al, 2010.;Bashir et al, 2011). These patients have relatively late onset vision loss, which may explain the lack of retinal phenotype in most USH mutant mice, whose lifespan is only about two years.…”

“…Type I (USH1) patients have congenital severe to profound deafness as well as vestibular dysfunction; Patients with USH2 exhibit congenital moderate degree of hearing loss and normal vestibular function; and those with USH3 display progressive hearing impairment and occasional vestibular dysfunction. The vision problem of all three types is manifested as retinitis pigmentosa (Hartong et al, 2006;Sadeghi et al, 2006;Fishman et al, 2007;Sandberg et al, 2008;Malm et al, 2011), showing early night and peripheral vision loss and eventual central vision loss.…”