Neurofibromatosis Type 1 May Induce Abnormal Retinal Pigment Epithelium Functioning

Retinal scan testing for glaucoma. Woman with her head resting in a machine (left) being used by an ophthalmologist (right) to scan the retinas of her eyes and examine them for signs of glaucoma. The retina is the light-sensitive layer at the back of the eye responsible for vision. Glaucoma is a build-up of pressure inside the eye causing blurring and blindness. The technique in use here is optical coherence tomography (OCT) using a confocal scanning laser ophthalmoscope (SLO) device. This machine is from the Optovue company. The results of the scan are shown on the screens and in image C028/1548.
Researchers suspect patients with neurofibromatosis type 1 experience a dysregulation of melanocytogenesis, inducing abnormal polarization on both sides of RPE.

Retinal pigment epithelium (RPE) functioning is abnormal in patients with neurofibromatosis type 1 (NF1), according to a study published in Investigative Ophthalmology & Visual Science.

The researchers conducted a prospective case-control study to evaluate the function of the RPE using electrooculography (EOG), comparing RPE function in patients with NF1 versus control participants ( Identifier NCT04153344). As a secondary goal, they also evaluated whether choroidal abnormalities correlated with RPE dysfunction in patients with NF1 with choroidal abnormalities.

All participants underwent complete ophthalmologic assessment with multimodal imaging, EOG, and full-field electroretinography. Case and control participants were matched for age. The primary outcome was the EOG light peak (LP)/dark trough (DT) ratio, also known as the Arden ratio.

The study included 20 patients with NF1 (n=10, with choroidal abnormalities and n=10 without choroidal abnormalities) and 10 healthy control participants. Patients had a median age of 10 years (range, 8-19). 

The researchers found that patients with NF1 had a significantly higher LP/DT ratio than control participants (3.02±0.52 vs 2.63±0.31; P =.02), with significantly lower DT values in patients with NF1 than in control participants (240 vs 325 µV; P =.02). They found no significant difference in the light peak values or peak latencies between the groups (P =.26). 

The team did not observe significant differences in the LP or DT values of the patients with and without choroidal abnormalities. In patients with choroidal abnormalities, they did not find any significant correlations between the median number or surface area of choroidal abnormalities and EOG parameters.

“This study confirms that patients with NF1 exhibit a supra-normal Arden ratio on EOG, which results from low DT amplitudes,” researchers explain. “We hypothesize that these responses are explained by a dysregulation of melanocytogenesis, inducing abnormal polarization on both sides of RPE (apical and basal membranes).”

The primary limitation noted for the study was the exclusion of all patients with clinical parameters that could have led to variability of values obtained during electrophysiologic assessment (strictly following the International Society for Clinical Electrophysiology of Vision guidelines).


Touzé R, Abitbol MM, Bremond-Gignac D, Robert MP. Function of the retinal pigment epithelium in patients with neurofibromatosis type 1. Invest Ophthalmol Vis Sci. 2022;63(4):6. doi:10.1167/iovs.63.4.6