Retinal Vascular Abnormalities related to Neurofibromatosis Type 1: Natural History and Classification by OCT Angiography in 473 Patients

PURPOSE: To analyze and classify neurofibromatosis type 1 (NF1) related retinal vascular abnormalities (RVAs), their natural history and correlation with disease severity, in a large cohort of patients.METHODS: This was an observational longitudinal study with prospective enrollment. Four hundred and seventy-three patients affected by NF1 and 150 age-matched healthy subjects were consecutively enrolled. RVAs were detected by means of near-infrared reflectance and studied by optical coherence tomography angiography (OCTA). The superficial vascular plexus (SVP) and the deep vascular complex (DVC) were quantitatively and qualitatively analyzed.RESULTS: We identified RVAs in 82 of 473 (17%) NF1 patients, but in none of the 150 healthy subjects. A comparison revealed that NF1 patients with RVAs showed a higher number of NF1 diagnostic criteria (4.3 ± 1.5 versus 3.9 ±1.5, respectively; p=0.02) than patients without RVAs. Three different RVA types were identified on OCTA: macrovascular angiomatosis of the sole SVP; macrovascular angiomatosis of the SVP combined with microvascular angiomatosis of the DVC; and combined macrovascular angiomatosis of both SVP and DVC. The prospective analysis of OCTA images showed no significant longitudinal evolution of RVAs (mean follow-up: 3.7 ± 2.8 years). A single patient developed de novo a single RVA, and two RVAs showed detectable changes during follow-up.CONCLUSION: In NF1 patients RVAs are a characteristic sign that correlates with a more severe systemic disease expression, usually remaining stable during time. OCTA allows for the identification of different RVAs subtypes.