Patients with X-linked retinitis pigmentosa due to RPGR mutations lose visual acuity and visual field more rapidly than do patients with dominant retinitis pigmentosa due to RHO mutations.

To determine whether a therapeutic dose of docosahexaenoic acid (DHA), an-3 fatty acid, will slow the course of retinal degeneration in adult patients with retinitis pigmentosa who are also receiving vitamin A. Design: Randomized, controlled, double-masked trial of 221 patients, aged 18 to 55 years, evaluated over a 4-year interval. Patients were given either 1200 mg/d of docosahexaenoic acid or control capsules. All were given 15000 IU/d of vitamin A (given as retinyl palmitate). Randomization considered genetic type and baseline dietary-3 fatty acid intake. Main Outcome Measures: The primary outcome measure was the total point score for the 30-2 program of the Humphrey field analyzer; secondary outcome measures were the total point score for the 30-2 and 30/60-1 programs combined, 30-Hz electroretinogram amplitude, and Early Treatment Diabetic Rentinopathy Study visual acuity. Results: No significant differences in decline in ocular function were found between the docosahexaenoic

INTRODUCTION Spinocerebellar ataxia type 7 is a neurodegenerative polyglutamine disease characterized by ataxia and retinal degeneration. The longitudinal course is unknown, and relationships between repeat expansion, clinical manifestations, and neuropathology remain uncertain. METHODS We followed 16 affected individuals of a 61-member kindred over 27 years with electroretinograms, neurological examinations including the Brief Ataxia Rating Scale, neuroimaging in 5, and autopsy in 4 cases. RESULTS We identified 4 stages of the illness. Stage 0; gene positive but phenotypically silent. Stage 1; no symptoms, but hyperreflexia and/or abnormal electroretinograms. Stage 2; symptoms and signs progress modestly. Stage 3; rapid clinical progression. CAG repeat length correlated inversely with age of onset of visual or motor signs (r=-0.74, p=0.002). Stage 3 rate of progression did not differ between cases (p=0.18). Electroretinograms correlated with Brief Ataxia Rating Scale score and were a biomarker of disease onset and progression. All symptomatic patients developed gait ataxia, extremity dysmetria, dysarthria, dysrhythmia, and oculomotor abnormalities. Funduscopy revealed pale optic discs and pigmentary disturbances. Visual acuity declined to blindness in those with longer CAG expansions. Hyperreflexia was present from Stage 1 onwards. Restless legs syndrome and sensory impairment were common. Neuropathological hallmarks were neuronal loss in cerebellar cortex, deep cerebellar nuclei, inferior olive, and anterior horns of the spinal cord, and axonal loss in spinocerebellar tracts, dorsal nerve roots and posterior columns. Retinal pathology included photoreceptor degeneration and disruption of retinal pigment epithelium. DISCUSSION Spinocerebellar ataxia type 7 evolves through 4 clinical stages; neuropathological findings underlie the clinical presentation; electroretinograms are a potential biomarker of disease progression.

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.