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 ¼ 11), central vision loss (n ¼ 1), or light-gazing (n ¼ 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 ¼ 11) were nondetectable (n ¼ 2; ages 31–60), reduced in a nonspecified pattern (n ¼ 2; ages 11–54), or showed rod–cone (n ¼ 6; ages 38–48) or cone–rod (n ¼ 1; age 29) dysfunction. Optical coherence tomography (n ¼ 4) showed retinal thinning but relative preservation of the (para-)foveal outer retinal layers in the second (n ¼ 1) and sixth decade of life (n ¼ 2), and profound chorioretinal degeneration from the eighth decade of life (n ¼ 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 ¼ 11), central vision loss (n ¼ 1), or light-gazing (n ¼ 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 ¼ 11) were nondetectable (n ¼ 2; ages 31–60), reduced in a nonspecified pattern (n ¼ 2; ages 11–54), or showed rod–cone (n ¼ 6; ages 38–48) or cone–rod (n ¼ 1; age 29) dysfunction. Optical coherence tomography (n ¼ 4) showed retinal thinning but relative preservation of the (para-)foveal outer retinal layers in the second (n ¼ 1) and sixth decade of life (n ¼ 2), and profound chorioretinal degeneration from the eighth decade of life (n ¼ 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074386274&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31448181
U2 - https://doi.org/10.1167/tvst.8.4.24
DO - https://doi.org/10.1167/tvst.8.4.24
M3 - Article
C2 - 31448181
SN - 2164-2591
VL - 8
JO - Translational Vision Science and Technology
JF - Translational Vision Science and Technology
IS - 4
M1 - 24
ER -