Cross-sectional studies have provided compelling evidence that NOTCH3 variant risk category is a major modifier of NOTCH3-SVD severity,11, -, 18 although this was not found in 2 studies of French patients.28,29 Prospective CADASIL follow-up studies taking into account NOTCH3 risk category have not been performed so far. Here, NOTCH3 is linked to snowflake vitreoretinal degeneration.