Early-onset foveal involvement in retinitis punctata albescens with mutations in RLBP1

摘要

Importance Retinitis punctata albescens (RPA) is an autosomal recessive form of retinitis pigmentosa characterized by white dotlike deposits in the fundus, in most cases caused by mutations in RLBP1. Objective To study disease progression and visual function in RPA. DESIGN We performed clinical and molecular investigations in patients with RPA at various ages, from November 5, 2003, through June 20, 2012, with no planned patient follow-up. Setting The National Reference Center for Genetic Sensory Diseases (Montpellier). Participants Eleven patients with RPA (mean age, 24 [range, 3-39] years) from 7 families and 11 control subjects undergoing evaluation. EXPOSURE Optical coherence tomography measurements. Main Outcomes And Measures Screening for mutations by polymerase chain reaction sequencing of the 9 RLBP1 exons. Patients underwent standard ophthalmic examination, fundus imaging, autofluorescence testing, Goldmann visual field measurement, optical coherence tomography, adaptive optics-based infrared fundus ophthalmoscopy, dark adaptometry, and electroretinography. Results We found 2 novel RLBP1 mutations (p.Tyr111X and p.Arg9Cys), and 8 patients from Morocco were homozygous for the recurrent 7.36-kilobase RLBP1 deletion of exons 7 through 9. All patients had night blindness (before age 6 years in 10). The dotlike deposits were generally dense but could be rare, appearing in adaptive optics as elongated structures with variable orientation and no foveal involvement.We found no specific refractive error, and visual acuity varied widely from normal (1.2) to counting fingers. Variable degrees of visual field impairment were present, and all patients had severely decreased electroretinographic responses with predominant rod impairment. No correlation between visual acuity (P =.27) or visual field and age (P =.08) was present. On optical coherence tomography, the mean (SD) central foveal (122 [23] vs 187 [30] μm in controls) and foveal (147 [19] vs 217 [17] μm) thicknesses were significantly (P 01) decreased, independently of age, whereas the retinal thickness at the 3-and 6-mm rings around the fovea progressively decreased with age. Mean (SD) cone number was normal in 1 patient aged 13 years (21 000/mm2 [2000/mm2]) but dropped to 10 500/mm2 (5244/mm2), 8667/mm2 (2944/mm 2), and 5833/mm2 (983/mm2) in 3 other patients aged 39, 32, and 29 years, respectively. Conclusions And Relevance Patients with RPA show variable degrees of foveal cone death, even at an early stage. This finding has implications for future treatment.