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Transl Vis Sci Technol. 2019 Aug 19;8(4):24. doi: 10.1167/tvst.8.4.24. eCollection 2019 Jul.

Long-Term Follow-Up of Retinal Degenerations Associated With LRAT Mutations and Their Comparability to Phenotypes Associated With RPE65 Mutations.

Author information

1
Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.
2
Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands.
3
Bartiméus, Diagnostic Center for Complex Visual Disorders, Zeist, the Netherlands.
4
Department of Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium.
5
Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
6
Department of Clinical Genetics, Academic Medical Center, Amsterdam, the Netherlands.
7
Ophthalmic Genetics & Visual Electrophysiology, Division of Ophthalmology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
8
The Netherlands Institute for Neuroscience (NIN-KNAW), Amsterdam, the Netherlands.

Abstract

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.

KEYWORDS:

cone-rod degeneration; disease progression; genetic diseases; retinitis pigmentosa

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