Function of the Retinal Pigment Epithelium in Patients With Neurofibromatosis Type 1

Abstract

Purpose: Retinal and choroidal abnormalities in neurofibromatosis type 1 (NF1) remain poorly studied. It has been reported, however, that the function of the retinal pigment epithelium (RPE) in NF1 was abnormal, with a supra-normal Arden ratio of the electro-oculogram (EOG). This study aims to evaluate the function of the RPE, using EOG, first in patients with NF1 compared to controls and second in patients with NF1 with choroidal abnormalities compared to patients with NF1 without choroidal abnormalities.

Methods: This prospective case-control study included 20 patients with NF1 (10 patients with choroidal abnormalities and 10 patients without) and 10 healthy patients, matched for age. A complete ophthalmologic assessment with multimodal imaging, an EOG, and a full-field electroretinogram were performed for each included patient. The main outcome measured was the EOG light peak (LP)/dark trough (DT) ratio.

Results: The LP/DT ratio was 3.02 ± 0.52 in patients with NF1 and 2.63 ± 0.31 in controls (P = 0.02). DT values were significantly lower in patients with NF1 than in controls (240 vs. 325 µV, P = 0.02), while light peak values were not significantly different (P = 0.26). No difference was found for peak latencies. No significant correlation between the surface and number of choroidal abnormalities and EOG parameters was demonstrated.

Conclusions: This study confirms the dysfunction of the RPE in patients with NF1, involving a lower DT and a corresponding higher LP/DT ratio. We hypothesize that this pattern may be due to a dysregulation of the melanocytogenesis, inducing a disruption in Ca2+ ion flux and an abnormal polarization of the RPE.

Conflict of interest statement

Disclosure: R. Touzé, None; M.M. Abitbol, None; D. Bremond-Gignac, None; M.P. Robert, None

Figures

Figure 1.

Typical supra-normal EOG results obtained in a child with NF1 (A) and a control (B). In the child with NF1, the dark trough occurred at 9 minutes with values of 163 µV for the right eye and 144 µV for the left eye, and the light peak occurred at 23 to 24 minutes with values of 611 µV for the right eye and 654 µV for the left eye with an LP/DT ratio of 3.74 and 4.54, respectively. In the healthy child, the dark trough occurred at 12 minutes with values of 260 µV for the right eye and 328 µV for the left eye, and the light peak occurred at 23 to 24 minutes with values of 746 µV for the right eye and 856 µV for the left eye with an LP/DT ratio of 2.87 and 2.61, respectively. OD, oeil droit meaning right eye; OG, oeil gauche meaning left eye.

Figure 2.

Boxplot of electro-oculogram values obtained between patients with NF1 and controls. Each value, including LP, DT, and LP/DT ratio, is represented. The first quartile is the bottom of the box and the third quartile the top of the box. The center line represents the median value; whiskers include the 5th to 95th percentiles of data; outliers are represented as black dots. P values are indicated above.

Figure 3.

Near-infrared imaging fundus in a 12-year-old boy with NF1: (A) right eye and (B) left eye. Typical patchy bright lesions were observed in both eyes, representing typical choroidal abnormalities (white arrow). Area of these abnormalities was 12.18 mm² on the right eye and 11.36 mm² on the left eye. Normal near-infrared imaging fundus in a healthy 11-year-old girl is presented for comparison: (C) right eye and (D) left eye.

Figure 4.

Comparative spectral-domain optical coherence tomography scans with EDI in children with NF1 and choroidal abnormalities (A), without choroidal abnormalities (B), and without NF1 (C). The subfoveal choroidal thickness was assessed in each patient in a single point located behind the fovea (black arrow). These scans compared choroidal thickness of a choroidal abnormality (red arrow, A) and correspondent area in a patient with NF1 but without a choroidal abnormality (red arrow, B) and control (red arrow, C). The opposite choroidal thickness, 2000 µm from the fovea temporally, was measured (white arrow). No statistical difference of choroidal thickness was observed between groups.