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

[PURPOSE] Several injectable hyaluronic acid dermal fillers exist in 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-L, Juvéderm Ultra, Juvéderm 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 to 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-min time point through 3 h time point, with continued gradual degradation through week 2. A mild dose response was found for Juvéderm and Restylane; however, a clear dose response was seen from 2.5 to 10 units for Voluma, with 2.5 units showing features more like those of saline only or no hyaluronidase control. 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, i.e., more than 20 units per 0.2 mL of filler. Restylane appeared to respond most readily to hyaluronidase, at the dose of even 2.5 units, but it also was fastest to dissolve on its own.