TY - JOUR
T1 - Long-Term Follow-Up of Retinal Degenerations Associated With LRAT Mutations and Their Comparability to Phenotypes Associated With RPE65 Mutations
AU - Talib, Mays
AU - van Schooneveld, Mary J
AU - van Duuren, Roos J G
AU - Van Cauwenbergh, Caroline
AU - Ten Brink, Jacoline B
AU - De Baere, Elfride
AU - Florijn, Ralph J
AU - Schalij-Delfos, Nicoline E
AU - Leroy, Bart P
AU - Bergen, Arthur A
AU - Boon, Camiel J F
PY - 2019
Y1 - 2019
N2 - Purpose: To investigate the natural history in patients with LRAT-associated retinal degenerations (RDs), in the advent of clinical trials testing treatment options.Methods: A retrospective cohort of 13 patients with LRAT-RDs.Results: Twelve patients from a genetic isolate carried a homozygous c.12del mutation. One unrelated patient carried a homozygous c.326G>T mutation. The mean follow-up time was 25.3 years (SD 15.2; range 4.8-53.5). The first symptom was nyctalopia (n = 11), central vision loss (n = 1), or light-gazing (n = 1), and was noticed in the first decade of life. Seven patients (54%) reached low vision (visual acuity < 20/67), four of whom reaching blindness (visual acuity < 20/400), respectively, at mean ages of 49.9 (SE 5.4) and 59.9 (SE 3.1) years. The fundus appearance was variable. Retinal white dots were seen in six patients (46%). Full-field electroretinograms (n = 11) were nondetectable (n = 2; ages 31-60), reduced in a nonspecified pattern (n = 2; ages 11-54), or showed rod-cone (n = 6; ages 38-48) or cone-rod (n = 1; age 29) dysfunction. Optical coherence tomography (n = 4) showed retinal thinning but relative preservation of the (para-)foveal outer retinal layers in the second (n = 1) and sixth decade of life (n = 2), and profound chorioretinal degeneration from the eighth decade of life (n = 1).Conclusions: LRAT-associated phenotypes in this cohort were variable and unusual, but generally milder than those seen in RPE65-associated disease, and may be particularly amenable to treatment. The window of therapeutic opportunity can be extended in patients with a mild phenotype.Translational Relevance: Knowledge of the natural history of LRAT-RDs is essential in determining the window of opportunity in ongoing and future clinical trials for novel therapeutic options.
AB - Purpose: To investigate the natural history in patients with LRAT-associated retinal degenerations (RDs), in the advent of clinical trials testing treatment options.Methods: A retrospective cohort of 13 patients with LRAT-RDs.Results: Twelve patients from a genetic isolate carried a homozygous c.12del mutation. One unrelated patient carried a homozygous c.326G>T mutation. The mean follow-up time was 25.3 years (SD 15.2; range 4.8-53.5). The first symptom was nyctalopia (n = 11), central vision loss (n = 1), or light-gazing (n = 1), and was noticed in the first decade of life. Seven patients (54%) reached low vision (visual acuity < 20/67), four of whom reaching blindness (visual acuity < 20/400), respectively, at mean ages of 49.9 (SE 5.4) and 59.9 (SE 3.1) years. The fundus appearance was variable. Retinal white dots were seen in six patients (46%). Full-field electroretinograms (n = 11) were nondetectable (n = 2; ages 31-60), reduced in a nonspecified pattern (n = 2; ages 11-54), or showed rod-cone (n = 6; ages 38-48) or cone-rod (n = 1; age 29) dysfunction. Optical coherence tomography (n = 4) showed retinal thinning but relative preservation of the (para-)foveal outer retinal layers in the second (n = 1) and sixth decade of life (n = 2), and profound chorioretinal degeneration from the eighth decade of life (n = 1).Conclusions: LRAT-associated phenotypes in this cohort were variable and unusual, but generally milder than those seen in RPE65-associated disease, and may be particularly amenable to treatment. The window of therapeutic opportunity can be extended in patients with a mild phenotype.Translational Relevance: Knowledge of the natural history of LRAT-RDs is essential in determining the window of opportunity in ongoing and future clinical trials for novel therapeutic options.
U2 - 10.1167/tvst.8.4.24
DO - 10.1167/tvst.8.4.24
M3 - Article
C2 - 31448181
VL - 8
SP - 24
JO - Translational Vision Science & Technology
JF - Translational Vision Science & Technology
SN - 2164-2591
IS - 4
ER -