ABSTRACT
PURPOSE: To study the rate of multifocal electroretinographic (mfERG) response amplitude changes and their relation to other parameters of disease development in retinitis pigmentosa (RP). METHODS: Twenty-three patients (9 men and 14 women) with clinically defined RP were included in the study. Disease progression was monitored during a period of up to 10 years by psychophysical techniques and Ganzfeld electroretinography. In addition, ERGs were recorded with a mfERG imaging system (VERIS; Electro-Diagnostic Imaging, Inc., Redwood City, CA). The black and white stimulus consisted of 61 hexagons covering a visual field of approximately 60 degrees x 55 degrees . Responses were analyzed according to concentric ring averages. RESULTS: The progression of visual field loss for target III4e was approximately 14.5%. Using the same type of regression model, the yearly progression according to the mfERG values was found to be approximately 6% to 10% in the outer three rings. Visual acuity (median 0.8) correlated well with the amplitude of the central segment of the mfERGs, ring 5 amplitudes of the mfERG strongly correlated with the scotopic Ganzfeld ERG mixed cone-rod response amplitude. However, in advanced cases, reliable mfERG responses could still be recorded, even if the ISCEV scotopic Ganzfeld ERG was not reproducible. MfERG ring 5 amplitudes as well as the Ganzfeld ERG mixed cone-rod response amplitude showed only a mild correlation with visual field area. CONCLUSIONS: The mfERG allows long-term follow-up of disease progression in retinitis pigmentosa. It does not replace, but complements psychophysical methods and could be used as an objective outcome measure in upcoming treatment studies involving patients with advanced retinal diseases.
Subject(s)
Electroretinography , Photoreceptor Cells, Vertebrate/physiology , Retinitis Pigmentosa/physiopathology , Vision Disorders/physiopathology , Visual Fields/physiology , Adolescent , Adult , Aged , Child , Color Vision Defects/physiopathology , Dark Adaptation , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retinitis Pigmentosa/diagnosis , Visual Acuity/physiology , Visual Field TestsABSTRACT
Usher syndrome (USH) is an autosomal recessive condition characterized by sensorineural hearing loss, vestibular dysfunction, and visual impairment due to retinitis pigmentosa. Truncating mutations in the cadherin-23 gene (CDH23) result in Usher syndrome type 1D (USH1D), whereas missense mutations affecting strongly conserved motifs of the CDH23 protein cause non-syndromic deafness (DFNB12). Four missense mutations constitute an exception from this genotype-phenotype correlation: they have been described in USH1 patients in homozygous state. Using a minigene assay, we have investigated these changes (c.1450G>C, p.A484P; c.3625A>G, p.T1209A; c.4520G>A, p.R1507Q; and c.5237G>A, p.R1746Q) for a possible impact on mRNA splicing which could explain the syndromic phenotype. While in silico analysis suggested impairment of splicing in all four cases, we found aberrant splicing for only one mutation, p.R1746Q. However, splicing was normal in case of p.A484P, p.T1209A and p.R1507Q. These three latter CDH23 missense mutations could interfere with functions of both, the auditory and the visual system. Alternatively, they could represent rare non-pathogenic polymorphisms.
