Abstract / Summary
Abstract Periorbital ageing is characterized by dynamic wrinkles, volume loss, and dermal quality decline. Injectable polynucleotides (PN) have emerged as biostimulatory agents for periorbital rejuvenation, and this review evaluates their efficacy and safety for this indication. The review was conducted per PRISMA 2020 guidelines and registered on PROSPERO (CRD420261288052). MEDLINE and Embase were searched from inception to 30 January 2026 for studies of adults receiving injectable PN for periorbital rejuvenation; no meta-analysis was performed given anticipated heterogeneity. Six studies (five randomized split-face trials, one prospective case series; n=350) met inclusion criteria, all conducted in Korean and Thai cohorts with Fitzpatrick III-V skin and predominantly middle-aged women (80-100% female). PN produced consistent short-term improvements in crow's feet severity and dermal quality metrics, with 40-70% of treated sides achieving at least a one-grade Crow's Feet Grading Scale improvement at 12 weeks, reflecting cross-trial heterogeneity rather than a single pooled effect. In two trials (n=30 and n=215), PN was non-inferior to polycaprolactone fillers for crow's feet correction; in one trial (n=30), PN showed favorable biophysical outcomes relative to hyaluronic acid. Safety was favorable throughout, but no study followed patients beyond 6 months. In these East Asian, predominantly female cohorts, PN demonstrates short-term efficacy and a favorable safety profile through 6 months for periorbital rejuvenation. Given the small number of studies, heterogeneity, and lack of longer-term follow-up, findings should be regarded as preliminary. Generalization beyond the populations and timeframes studied awaits larger, longer-term, ethnically diverse trials with direct comparison to established modalities.