Combined Application of Hyaluronidase and Collagenase for Late-Onset Edema in Periocular Area After Hyaluronic Acid Volume Repositioning: A Six-Case Retrospective Review

Abstract

Background and objective: Although generally low-risk, hyaluronic acid (HA) dermal fillers can lead to late-onset edema, particularly in the periocular region. This condition typically manifests three to four months post-injection and requires specialized management, usually with hyaluronidase. However, increased use of hyaluronidase has resulted in instances of post-hyaluronidase syndrome, leading to unaesthetic outcomes. This study presents a retrospective case series that utilizes a novel technique combining two enzymes to improve late-onset edema and prevent post-hyaluronidase syndrome development. Methods: From 2019 to 2024, six patients in our aesthetic clinic received a novel therapeutic approach involving co-administration of 1,500 IU of hyaluronidase and collagenase with a cannula to address late-onset edema in the periocular area. Results: The combination of high-dose hyaluronidase and low-dose collagenase improved late-onset edema in all patients after a single treatment. Statistical analysis showed a significant improvement in aesthetic scores (P < 0.05), with effect sizes of 0.89 for Hirmand, 1.3 for the Teoxane Infraorbital Hollows Scale (TIOHS), and 1.2 for O'Mahoney's photo-numeric scale. No post-hyaluronidase syndrome or complications were observed. Conclusions: This combined technique utilizing 1,500 IU of hyaluronidase and collagenase GH PB220 from Pbserum (Madrid, Spain) effectively achieves significant aesthetic improvements with a high safety profile, offering a promising alternative for managing late-onset edema after HA dermal filler treatments.