Retinal Vasoreactivity is a Marker for Cerebral Small Vessel Disease Progression

This is a prospective, observational nested pilot randomized controlled study to discover retinal biomarkers that would predict cerebral small vessel disease progression, and evaluate the safety/efficacy of cilostazols in slowing SVD progression. Twenty CADASIL, 40 sWMD, 20 lobar CMB, and 20 age-matched healthy controls from the Mayo Clinic Florida Familial Cerebrovascular Disease Registry and neurology clinic will be recruited. All participants will undergo OCTA retinal scan, MRI-BOLD brain scan, cognitive battery evaluation, and blood sample at baseline and a 12-month follow-up visit. Key outcome measures are: RVR, CVR, cognition, WMH volume, and CMB volume. The 40 patients diagnosed in the course of routine clinical care with sWMD will be randomized in 1:1 ratio to receive cilostazol 100mg bid (or 50 mg bid if taking medications known to affect metabolism of cilostazol) or no cilostazol, and followed for WMD progression, and secondarily for changes in cognition, RVR and CVR. Flow diagram below outlines the study design. Note that in addition to what is shown in the trial flow diagram, patients will have telephone visits between baseline and 12 month clinic visits biweekly for 3 months and then monthly thereafter. These visits will consist of a survey for adverse events and at the 1-, 3-, 6- and 9-month telephone visits patients will also get a modified Rankin scale assessment, a Six-item screener (cognitive assessment) and a PHQ-2 (depression screen).