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

Mays Talib; Mary J van Schooneveld; Roos J G van Duuren; Caroline Van Cauwenbergh; Jacoline B Ten Brink; Elfride De Baere; Ralph J Florijn; Nicoline E Schalij-Delfos; Bart P Leroy; Arthur A Bergen; Camiel J F Boon

doi:10.1167/tvst.8.4.24

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

Mays Talib, Mary J van Schooneveld, Roos J G van Duuren, Caroline Van Cauwenbergh, Jacoline B Ten Brink, Elfride De Baere, Ralph J Florijn, Nicoline E Schalij-Delfos, Bart P Leroy, Arthur A Bergen, Camiel J F Boon

Netherlands Institute for Neuroscience (NIN)

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

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.

Original language	English
Pages (from-to)	24
Journal	Translational Vision Science & Technology
Volume	8
Issue number	4
DOIs	https://doi.org/10.1167/tvst.8.4.24
Publication status	Published - 2019

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10.1167/tvst.8.4.24

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Talib, M., van Schooneveld, M. J., van Duuren, R. J. G., Van Cauwenbergh, C., Ten Brink, J. B., De Baere, E., Florijn, R. J., Schalij-Delfos, N. E., Leroy, B. P., Bergen, A. A., & Boon, C. J. F. (2019). Long-Term Follow-Up of Retinal Degenerations Associated With LRAT Mutations and Their Comparability to Phenotypes Associated With RPE65 Mutations. Translational Vision Science & Technology, 8(4), 24. https://doi.org/10.1167/tvst.8.4.24

Talib, Mays ; van Schooneveld, Mary J ; van Duuren, Roos J G ; Van Cauwenbergh, Caroline ; Ten Brink, Jacoline B ; De Baere, Elfride ; Florijn, Ralph J ; Schalij-Delfos, Nicoline E ; Leroy, Bart P ; Bergen, Arthur A ; Boon, Camiel J F. / Long-Term Follow-Up of Retinal Degenerations Associated With LRAT Mutations and Their Comparability to Phenotypes Associated With RPE65 Mutations. In: Translational Vision Science & Technology. 2019 ; Vol. 8, No. 4. pp. 24.

@article{268303000f5047d6b3e35a12716f42d5,

title = "Long-Term Follow-Up of Retinal Degenerations Associated With LRAT Mutations and Their Comparability to Phenotypes Associated With RPE65 Mutations",

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.",

author = "Mays Talib and {van Schooneveld}, {Mary J} and {van Duuren}, {Roos J G} and {Van Cauwenbergh}, Caroline and {Ten Brink}, {Jacoline B} and {De Baere}, Elfride and Florijn, {Ralph J} and Schalij-Delfos, {Nicoline E} and Leroy, {Bart P} and Bergen, {Arthur A} and Boon, {Camiel J F}",

year = "2019",

doi = "10.1167/tvst.8.4.24",

language = "English",

volume = "8",

pages = "24",

journal = "Translational Vision Science & Technology",

issn = "2164-2591",

publisher = "Association for Research in Vision and Ophthalmology Inc.",

number = "4",

}

Talib, M, van Schooneveld, MJ, van Duuren, RJG, Van Cauwenbergh, C, Ten Brink, JB, De Baere, E, Florijn, RJ, Schalij-Delfos, NE, Leroy, BP, Bergen, AA & Boon, CJF 2019, 'Long-Term Follow-Up of Retinal Degenerations Associated With LRAT Mutations and Their Comparability to Phenotypes Associated With RPE65 Mutations', Translational Vision Science & Technology, vol. 8, no. 4, pp. 24. https://doi.org/10.1167/tvst.8.4.24

Long-Term Follow-Up of Retinal Degenerations Associated With LRAT Mutations and Their Comparability to Phenotypes Associated With RPE65 Mutations. / Talib, Mays; van Schooneveld, Mary J; van Duuren, Roos J G; Van Cauwenbergh, Caroline; Ten Brink, Jacoline B; De Baere, Elfride; Florijn, Ralph J; Schalij-Delfos, Nicoline E; Leroy, Bart P; Bergen, Arthur A; Boon, Camiel J F.

In: Translational Vision Science & Technology, Vol. 8, No. 4, 2019, p. 24.

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

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 -

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

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