Reversing Facial Fillers: How Much Hyaluronidase Is Needed to Dissolve Unwanted Filler?

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Hyaluronic acid (HA) fillers are among the most commonly injected soft-tissue fillers worldwide. However, even with proper technique, there may be instances in which the filler becomes visible (Tyndall effect) or edematous, prompting the need to dissolve it. Not all HA fillers are identical; many differ in their degree of cross-linking or classification as monophasic or biphasic, which may affect the success in dissolving them with hyaluronidase. Rao et al (J Drugs Dermatol. 2014;13:1053-1056) published a study that looked at 2 commonly used hyaluronidase agents and how well they dissolved 4 commonly used HA fillers in the United States.

Rao et al performed an in vitro study using Vitrase (ovine testicular hyaluronidase)(Bausch & Lomb Incorporated) and Hylenex (recombinant human hyaluronidase)(Halozyme Therapeutics). The HA fillers tested were Restylane (Galderma Laboratories, LP), Juvéderm and Juvéderm Voluma (Allergan), and Belotero (Merz Aesthetics).

Phase 1 of the study looked at the volume of hyaluronidase on 3 of 4 fillers. The researchers utilized 0.1 mL of Vitrase or Hylenex to treat 0.2 mL of Restylane, Belotero, and Juvéderm. A control slide was kept for each filler. For Vitrase, 0.1 mL is 20 U of hyaluronidase. For Hylenex, 0.1 mL is 15 U of hyaluronidase. The filler and hyaluronidase were mixed together for 10 seconds using a 27-gauge needle. Photograph assessment of the slides was taken at 1 and 5 minutes.

Phase 2 of the study looked at the number of units of hyaluronidase on all 4 fillers. For this phase, 15 U and 30 U of Hylenex were mixed with 0.2 mL aliquots of each filler. Photographs and qualitative observations were taken at 1 and 5 minutes. The aliquots were observed for a total of 15 minutes.

For phase 1, the 2 hyaluronidase agents worked similarly on all 3 HA fillers. The greatest effect on dissolving or changing the shape of a filler was on Restylane, followed by Juvéderm and Belotero (a monophasic filler). The greatest effect was in the first minute and continued through the fifth minute. Even at 5 minutes, Belotero maintained most of its shape.

Phase 2 showed similar results with Restylane reacting the most to the hyaluronidase, followed by Juvéderm Voluma, Juvéderm, and Belotero. The higher dose (30 U) of hyaluronidase had a more dramatic effect on all fillers compared to the lower dose (15 U). Results were time dependent with the greatest changes seen at 5 minutes as opposed to 1 minute. The results of the 15-minute observation did not show any further changes. Belotero also maintained most of its shape during this phase.

What’s the issue?

With the increased number of HA fillers coming onto the market, it will become more important to understand the interaction between HA fillers and hyaluronidase. Hyaluronic acid fillers will vary in their degree of cross-linking, water absorption, and classification as monophasic (cohesive) or biphasic. Oftentimes, it is not until we use fillers in off-label manners that we realize some unintended consequences. We realized all too quickly that fillers, such as Restylane, placed superficially under eyelid skin gave an unsightly Tyndall effect. We then relied on hyaluronidase injections to resolve this issue. Furthermore, we learned that Juvéderm Ultra Plus XC could hold approximately 300% of its weight in water, causing unsightly eyelid edema in some patients. Luckily, the use of hyaluronidase can be a saving grace for physicians. However, the success of hyaluronidase injections varies. From the results of this study, it may be true that certain fillers need higher volumes or a higher number of units than other fillers to dissolve them. I would like to see this study expanded as newer HA fillers are brought onto the market.

Have you found that you have had to use varying amounts of hyaluronidase to address different filler complications?

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