TY - JOUR
T1 - Genotypic and Phenotypic Characteristics of CRB1-Associated Retinal Dystrophies: A Long-Term Follow-up Study
AU - Talib, Mays
AU - van Schooneveld, Mary J.
AU - van Genderen, Maria M.
AU - Wijnholds, Jan
AU - Florijn, Ralph J.
AU - ten Brink, Jacoline B.
AU - Schalij-Delfos, Nicoline E.
AU - Dagnelie, Gislin
AU - Cremers, Frans P. M.
AU - Wolterbeek, Ron
AU - Fiocco, Marta
AU - Thiadens, Alberta A.
AU - Hoyng, Carel B.
AU - Klaver, Caroline C.
AU - Bergen, Arthur A.
AU - Boon, Camiel J. F.
PY - 2017
Y1 - 2017
N2 - To describe the phenotype, long-term clinical course, clinical variability, and genotype of patients with CRB1-associated retinal dystrophies. Retrospective cohort study. Fifty-five patients with CRB1-associated retinal dystrophies from 16 families. A medical record review of 55 patients for age at onset, medical history, initial symptoms, best-corrected visual acuity, ophthalmoscopy, fundus photography, full-field electroretinography (ffERG), Goldmann visual fields (VFs), and spectral-domain optical coherence tomography. Age at onset, visual acuity survival time, visual acuity decline rate, and electroretinography and imaging findings. A retinitis pigmentosa (RP) phenotype was present in 50 patients, 34 of whom were from a Dutch genetic isolate (GI), and 5 patients had a Leber congenital amaurosis phenotype. The mean follow-up time was 15.4 years (range, 0-55.5 years). For the RP patients, the median age at symptom onset was 4.0 years. In the RP group, median ages for reaching low vision, severe visual impairment, and blindness were 18, 32, and 44 years, respectively, with a visual acuity decline rate of 0.03 logarithm of the minimum angle of resolution per year. The presence of a truncating mutation did not alter the annual decline rate significantly (P = 0.75). Asymmetry in visual acuity was found in 31% of patients. The annual VF decline rate was 5% in patients from the genetic isolate, which was significantly faster than in non-GI patients (P < 0.05). Full-field electroretinography responses were extinguished in 50% of patients, were pathologically attenuated without a documented rod or cone predominance in 30% of patients, and showed a rod-cone dysfunction pattern in 20% of RP patients. Cystoid fluid collections in the macula were found in 50% of RP patients. Mutations in the CRB1 gene are associated with a spectrum of progressive retinal degeneration. Visual acuity survival analyses indicate that the optimal intervention window for subretinal gene therapy is within the first 2 to 3 decades of life
AB - To describe the phenotype, long-term clinical course, clinical variability, and genotype of patients with CRB1-associated retinal dystrophies. Retrospective cohort study. Fifty-five patients with CRB1-associated retinal dystrophies from 16 families. A medical record review of 55 patients for age at onset, medical history, initial symptoms, best-corrected visual acuity, ophthalmoscopy, fundus photography, full-field electroretinography (ffERG), Goldmann visual fields (VFs), and spectral-domain optical coherence tomography. Age at onset, visual acuity survival time, visual acuity decline rate, and electroretinography and imaging findings. A retinitis pigmentosa (RP) phenotype was present in 50 patients, 34 of whom were from a Dutch genetic isolate (GI), and 5 patients had a Leber congenital amaurosis phenotype. The mean follow-up time was 15.4 years (range, 0-55.5 years). For the RP patients, the median age at symptom onset was 4.0 years. In the RP group, median ages for reaching low vision, severe visual impairment, and blindness were 18, 32, and 44 years, respectively, with a visual acuity decline rate of 0.03 logarithm of the minimum angle of resolution per year. The presence of a truncating mutation did not alter the annual decline rate significantly (P = 0.75). Asymmetry in visual acuity was found in 31% of patients. The annual VF decline rate was 5% in patients from the genetic isolate, which was significantly faster than in non-GI patients (P < 0.05). Full-field electroretinography responses were extinguished in 50% of patients, were pathologically attenuated without a documented rod or cone predominance in 30% of patients, and showed a rod-cone dysfunction pattern in 20% of RP patients. Cystoid fluid collections in the macula were found in 50% of RP patients. Mutations in the CRB1 gene are associated with a spectrum of progressive retinal degeneration. Visual acuity survival analyses indicate that the optimal intervention window for subretinal gene therapy is within the first 2 to 3 decades of life
U2 - https://doi.org/10.1016/j.ophtha.2017.01.047
DO - https://doi.org/10.1016/j.ophtha.2017.01.047
M3 - Article
C2 - 28341475
SN - 0161-6420
VL - 124
SP - 884
EP - 895
JO - Ophthalmology
JF - Ophthalmology
IS - 6
ER -