Prospective, in vivo evaluation of three different hyaluronic acid gels to varying doses of hyaluronidase with long-term follow up

Summary Purpose Several injectable hyaluronic acid dermal fillers exist on the market, each with different rheologic and cross-linking properties. Their reversibility is useful for managing complications. We sought to determine the response of three different hyaluronic acid gels to varying doses of hyaluronidase. Methods Each of 18 arms of nine subjects were prospectively randomized to receive intradermal injections of hyaluronic acid gel (Restylane, Juvederm, or Voluma). Seven sites on each arm were randomized to receive 0.2 mL of hyaluronic acid gel in anticipation of dissolution 1 week later with varying doses of hyaluronidase (Hylenex), 2.5, 5, 10, or 20 units, or be a control site. The outcome measures of diameter, elevation and firmness were measured pre-injection, and at varying time points to beyond 4 years. Subjects, graders, and injectors were masked. Results The most dramatic changes for all fillers occurred starting at the 30-minute time point through hour three, with continued gradual degradation through week two. A mild dose response was found for Juvederm and Restylane; however, a clear dose response was seen from 2.5 to 10 units for Voluma, with 2.5 units behaving more like saline only or no hyaluronidase controls. One Restylane arm had controls lasting four years. Conclusions All fillers had a dose response, with Voluma exhibiting it most clearly. Voluma required higher doses of hyaluronidase for dissolution, more than 20 units per 0.2 mL of filler. Restylane appeared to respond most quickly to hyaluronidase, even 2.5 units, but it also was fastest to dissolve on its own.