A Prospective, Randomized, Active-Controlled, Evaluator-Blinded, Noninferiority Clinical Trial Examining a Non-Cross-Linked Bovine-Derived Type I/III Collagen Filler Combined with Hyaluronic Acid for Periocular Rejuvenation

Abstract Background The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERM TM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane ® (produced by Galderma SA, Switzerland) were used as the primary treatments. Objectives This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Methods Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Results Compared with monotherapies, the combination therapy yielded superior outcomes in terms of periocular volume restoration and longevity. The combination therapy effectively addressed both structural support (via periosteal injections) and superficial rejuvenation (via subdermal placement) while significantly reducing the incidence of the Tyndall effect in the HA monotherapy group. The combination therapy showed extended durability compared with collagen monotherapy. Conclusions The combination of collagen and HA offers a comprehensive approach for periocular rejuvenation. This method combines the volumizing benefits of HA with the tissue-regenerative properties of collagen. Furthermore, this approach minimizes complications while enhancing treatment longevity, thus establishing a new standard for minimally invasive periocular rejuvenation. Level of Evidence I This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .