Long‐Term Safety of Intradermal Polynucleotides in the Periocular Region: A Retrospective Study

ABSTRACT Background The use of polynucleotides (PN) has increased significantly in aesthetic medicine due to their regenerative properties and favorable short‐term safety profile. However, evidence regarding their long‐term safety, particularly in real‐world clinical practice, remains limited. Objective To evaluate the short‐ and long‐term safety of intradermal polynucleotide treatment (PN‐HPT) in the periocular region based on routine clinical practice. Methods A retrospective observational study was conducted through medical record review. Patients consecutively treated with PN‐HPT for periocular rejuvenation between January and March 2024 were included. This inclusion period was defined to ensure a minimum available timeframe of 24 months from the first treatment session at the time of data analysis. All patients completed an initial protocol of three sessions, administered at 4‐week intervals. Polynucleotides (PN‐HPT 7.5 mg/mL) were administered intradermally using a 33G needle, with 1 mL injected per periocular side. Data on treatment sessions and adverse events were collected from clinical records. As part of routine clinical care, all patients were systematically contacted 24 h after each treatment session to assess early adverse events, and underwent at least one in‐person evaluation approximately 1 month after the final session. Subsequently, clinical records of all included patients were reviewed up to March 2026 to identify any additional or delayed adverse events. Safety assessment was based on documented events during routine clinical practice. Results A total of 23 patients were included, accounting for 91 treatment sessions between January 2024 and March 2026. Fifteen patients (65.2%) underwent additional sessions beyond the initial protocol, reflecting repeated exposure under real‐world conditions. Only two mild and self‐limited adverse events were documented: one case of transient periocular edema and one case of prolonged intradermal papules. No moderate or severe adverse events were recorded. Importantly, no delayed adverse events were identified in the medical records during the study timeframe. All patients continued receiving care during this period, and no additional treatment‐related adverse events were documented. Conclusions In this retrospective real‐world study, PN‐HPT demonstrated a favorable safety profile in the periocular region, with minimal and transient adverse events and no evidence of delayed complications despite repeated treatments. These findings support the tolerability of polynucleotides in routine clinical practice. Further prospective studies with larger sample sizes and standardized follow‐up are warranted to confirm long‐term safety.