Neurofibromatosis Type 1 (NF1)–Related Ocular Signs: New Insights on Their Prevalence, Incidence, and Genotype-Phenotype Correlation in NF1 Children

PURPOSE: To assess, in a large pediatric population affected by neurofibromatosis type 1 (NF1), the prevalence, incidence, age of onset, and genotype correlation of the main NF1-related ocular signs, including optic pathway glioma (OPG), Lisch nodules (LNs), choroidal abnormalities (CAs), and retinal vascular abnormalities (RVAs). METHODS: NF1 patients ≤16 years old followed at our institution between 2010 and 2022 were included. Presence of NF1-related ocular signs was assessed at baseline and during follow-up evaluations through slit lamp observation (LNs), near-infrared imaging (CAs and RVAs), and neuroimaging revision (OPG). Patients were categorized according to their genetic variant. RESULTS: A total of 237 patients were enrolled. Among those, 204 underwent at least 1 follow-up and genetic test was available for 210. Prevalence of OPG, LNs, CAs, and RVAs at baseline was, respectively, 20.7%, 43.5%, 46.8%, and 6.8%. Their incidence during follow-up was 6.4%, 22.4%, 21.4%, and 5.4%, respectively, and the mean age at onset was 6.3±3.6, 7.1±3.0, 6.4±3.0, and 6.6±2.9 years. Patients with truncating mutations presented a higher number of ocular signs than those with non-truncating mutations (1.7±1.0 vs 0.9±0.9, P =.0019). CONCLUSIONS: Data on prevalence and incidence of NF1-related ocular signs in pediatric patients evidences that the development of these signs seems negligible after the age of 7. LNs and CAs seem to develop independently and, therefore, can be considered as two separate diagnostic criteria. Truncating mutations correlate with a higher number of NF1-related ocular signs phenotype. Note: Publication of this article is sponsored by the American Ophthalmological Society.