Neurofibromatosis Type 1 Detectable Through Functional Abnormalities

Dysfunction in the retinal pigment epithelium (RPE) is associated with lower dark trough (DT) and higher light peak (LP)/DT ratio on electro-oculogram (EOG) testing in patients with neurofibromatosis type one (NF1), according to a prospective case-control study published in Retina. 

Patients (n=20) with NF1 and healthy patients placed into a control group (n=10) were recruited for this study at the Hospital Necker–Enfants Malades in France in 2020. All participants underwent clinical and electrophysiology evaluations and retinal imaging. Researchers compared the RPE functioning between the patient and control groups and between patients with (n=10) and without (n=10) choroidal abnormalities (CA).

The CA, no CA, and control cohorts had boy-to-girl ratios of 5/5, 2/8, and 6/4, and they were aged median 10 (range, 8-19), 9 (range, 8-12), and 11.9 (range, 8-16.4) years, respectively. The 3 groups all had visual acuity of 0.0 logarithm of the minimum angle of resolution (logMAR).

Among the NF1 group, more patients with CAs had Lisch nodules (70% vs 60%) and fewer had glioma (30% vs 40%), respectively. For patients with CAs, the median number of abnormalities was 10 (range, 2-21) with a median area of 10.6 (range, 0.66-57.64) mm².

Compared with controls, the patients with NF1 had significantly lower DT (mean, 240 vs 325 μV; P =.02) and higher LP/DT ratio (mean, 3.02 vs 2.63; P =.02) but no difference in LP (mean, 747 vs 850 μV; P =.26), respectively. Among the NF1 group, no differences were observed on the basis of CAs (all P ≥.72).

Comparing controls with only the patients with CAs, the difference in DT (mean, 239 vs 325 μV; P <.01) and LP/DT ratio (mean, 3.03 vs 2.63; P =.01) were even more pronounced, respectively.

A potential limitation of this study was the variability of values obtained during electrophysiologic assessment.

“We hypothesize that the disruption in melanocytogenesis observed in patients with NF1 results in an RPE dysfunction characterized by low DT amplitudes and supra-normal EOG,” according to the study authors. “Disruption in melanocytogenesis and abnormal macromelanosomes are present in both patients with NF1 and patients with OA, who both exhibit a similar EOG pattern, which likely results from a comparable disruption in Ca2+ ion flux.”