Long-Term Follow-Up of Retinal Degenerations Associated With Mutations and Their Comparability to Phenotypes Associated With Mutations.

Purpose: To investigate the natural history in patients with -associated retinal degenerations (RDs), in the advent of clinical trials testing treatment options.

Methods: A retrospective cohort of 13 patients with -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 ( = 11), central vision loss ( = 1), or light-gazing ( = 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 ( = 11) were nondetectable ( = 2; ages 31-60), reduced in a nonspecified pattern ( = 2; ages 11-54), or showed rod-cone ( = 6; ages 38-48) or cone-rod ( = 1; age 29) dysfunction. Optical coherence tomography ( = 4) showed retinal thinning but relative preservation of the (para-)foveal outer retinal layers in the second ( = 1) and sixth decade of life ( = 2), and profound chorioretinal degeneration from the eighth decade of life ( = 1).

Conclusions: -associated phenotypes in this cohort were variable and unusual, but generally milder than those seen in -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 -RDs is essential in determining the window of opportunity in ongoing and future clinical trials for novel therapeutic options.