Original Investigation | Clinical Sciences

Early-Onset Foveal Involvement in Retinitis Punctata Albescens With Mutations in RLBP1

Elodie Dessalces, BS, EBOD1; Béatrice Bocquet, PhD2,3,4; Jérôme Bourien, PhD2,3,4; Xavier Zanlonghi, MD5; Robert Verdet, MD6; Isabelle Meunier, MD, PhD1,2,3,4; Christian P. Hamel, MD, PhD1,2,3,4
[+] Author Affiliations
1Genetics of Sensory Diseases, Centre Hospitalier Régional Universitaire de Montpellier, Montpellier, France
2Institut des Neurosciences de Montpellier, Institut National de la Santé et de la Recherche Médicale (INSERM) U1051, Hôpital Saint-Eloi, Montpellier, France
3INSERM U1051, Université Montpellier 1, Montpellier, France
4INSERM U1051, Université Montpellier 2, Montpellier, France
5ElectroDiagnostic Imaging Unit, Low Vision Center, Clinique Sourdille, Nantes, France
6currently in private practice, Avignon, France
JAMA Ophthalmol. 2013;131(10):1314-1323. doi:10.1001/jamaophthalmol.2013.4476.
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Importance  Retinitis punctata albescens (RPA) is an autosomal recessive form of retinitis pigmentosa characterized by white dotlike deposits in the fundus, in most cases caused by mutations in RLBP1.

Objective  To study disease progression and visual function in RPA.

Design  We performed clinical and molecular investigations in patients with RPA at various ages, from November 5, 2003, through June 20, 2012, with no planned patient follow-up.

Setting  The National Reference Center for Genetic Sensory Diseases (Montpellier).

Participants  Eleven patients with RPA (mean age, 24 [range, 3-39] years) from 7 families and 11 control subjects undergoing evaluation.

Exposure  Optical coherence tomography measurements.

Main Outcomes and Measures  Screening for mutations by polymerase chain reaction sequencing of the 9 RLBP1 exons. Patients underwent standard ophthalmic examination, fundus imaging, autofluorescence testing, Goldmann visual field measurement, optical coherence tomography, adaptive optics–based infrared fundus ophthalmoscopy, dark adaptometry, and electroretinography.

Results  We found 2 novel RLBP1 mutations (p.Tyr111X and p.Arg9Cys), and 8 patients from Morocco were homozygous for the recurrent 7.36-kilobase RLBP1 deletion of exons 7 through 9. All patients had night blindness (before age 6 years in 10). The dotlike deposits were generally dense but could be rare, appearing in adaptive optics as elongated structures with variable orientation and no foveal involvement. We found no specific refractive error, and visual acuity varied widely from normal (1.2) to counting fingers. Variable degrees of visual field impairment were present, and all patients had severely decreased electroretinographic responses with predominant rod impairment. No correlation between visual acuity (P = .27) or visual field and age (P = .08) was present. On optical coherence tomography, the mean (SD) central foveal (122 [23] vs 187 [30] µm in controls) and foveal (147 [19] vs 217 [17] µm) thicknesses were significantly (P < .01) decreased, independently of age, whereas the retinal thickness at the 3- and 6-mm rings around the fovea progressively decreased with age. Mean (SD) cone number was normal in 1 patient aged 13 years (21 000/mm2 [2000/mm2]) but dropped to 10 500/mm2 (5244/mm2), 8667/mm2 (2944/mm2), and 5833/mm2 (983/mm2) in 3 other patients aged 39, 32, and 29 years, respectively.

Conclusions and Relevance  Patients with RPA show variable degrees of foveal cone death, even at an early stage. This finding has implications for future treatment.

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Figure 1.
Pedigrees of 7 Families With Retinitis Punctata Albescens and RLBP1 Mutations

Squares indicate male; circles, female; and plus sign, wild-type allele. Blackened symbols are individuals affected with retinitis punctata albescens. A double horizontal line between the mating pair indicates consanguinity, and black arrows, probands. The patient numbers show the generation in roman numerals and the order in the generation in arabic numbers. The genotype of the tested patients is indicated.

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Figure 2.
Fundus Images of Patients With Retinitis Punctata Albescens

Pedigrees for each patient are given in Figure 1. A and B, Patient III-2 from family MTP1633 and patient II-1 from family MTP1254, respectively, show widespread white dotlike deposits throughout the fundus. C, Patient III-6 from family MTP1838 shows foveal sparing of the white deposits. D, Patient II-1 from family MTP857 has widespread white deposits. E, Patient II-3 from family MTP857 has only a few bone spicule-shaped pigment deposits (arrow). F, The same patient has a few white deposits on the superior temporal vascular arcade area of the left eye (arrow). G, Patient II-3 from family MTP1789 has an abnormal foveal reflex. H, Patient II-3 from family MTP857 has foveal and perifoveal atrophy. I, Patient IV-1 from family MTP1838 has an advanced disease stage with scallop-shaped peripheral atrophic spots containing pigment deposits, foveal atrophy, a moderately pale optic disc, and narrowing of the retinal vessels. J and K, A color photograph and autofluorescence, respectively, of the macular area in patient II-1 from family MTP857. Insets show magnification of spots of decreased autofluorescence that do not exactly correspond to white dotlike deposits. L and M, Autofluorescence and a color photograph, respectively, of the macular area in patient II-1 from family MTP1254. Insets show magnification of heterogeneous autofluorescence and white dotlike deposits in part M that are not localized in part L.

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Figure 3.
Retinal Thickness of the Macular Area of Patients With Retinitis Punctata Albescens

A, Fundus image indicates foveal thickness (crossing of the axes) and thickness at the inner (3-mm) and outer (6-mm) rings along the vertical and horizontal axes. B and C, Retinal thickness of the 22 eyes (11 patients) along the vertical and horizontal axes, respectively, compared with 22 eyes from 11 healthy control subjects shows significant differences at the fovea and 3-mm ring. aP < .001.bP < .01.

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Figure 4.
Visual Function of Patients With Retinitis Punctata Albescens as a Function of Age

A, Mean visual acuity of both eyes of the 11 patients as a function of age. B, Retinal thickness of the 22 eyes (11 patients) was measured in the central fovea, in the fovea, and at the 3- and 6-mm rings in the superior, temporal, inferior, and nasal quadrants and plotted as a function of age. C, Percentage of the remaining visual field as determined by the Goldmann V-4-e isopter for 22 eyes as a function of age.

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Figure 5.
Adaptive Optics–Based Infrared Fundus Ophthalmoscopy Images of the Parafoveal Area

Family and patient numbers (or normal for control subjects), visual acuity, and age in years are indicated at the top of each image. A, C, and D, Patients have an abnormal cone mosaic. B, Control subject with a normal cone mosaic. E, White dotlike deposits. F, Visualization and magnification (white box) of the image in part E. G, No dotlike deposits are found in the fovea (right side of the picture). H, Similar area in a control.

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