PDRN for Periorbital Rejuvenation: Pilot Study on Under-Eye Skin Quality (2021)

Key Findings

• Intradermal PDRN micro-injections in the periorbital region reduced dark circle severity scores by 38.4% (p<0.01) and infraorbital wrinkle depth by 27.6% (p<0.05) at 16 weeks compared to baseline ^[1][4].
• Ultrasound dermoscopy revealed a statistically significant increase in periorbital dermal thickness (+18.2%, p<0.01) in the PDRN group versus 3.4% in the control group ^[1][5].
• PDRN's A2A receptor-mediated stimulation of fibroblast proliferation and collagen synthesis provides a biologically plausible mechanism for periorbital skin quality improvement ^[2][3].

Abstract

This prospective, controlled pilot study evaluated the efficacy and safety of intradermal polydeoxyribonucleotide (PDRN) injections for periorbital skin rejuvenation in patients presenting with infraorbital dark circles, fine wrinkles, and thin skin around the eyes ^[1][4]. Forty-two subjects (34 female, 8 male; mean age 43.7 years) were randomized 1:1 to receive either PDRN (5.625 mg/3 mL) or normal saline via micro-droplet intradermal injections in the periorbital region over 6 sessions at 2-week intervals ^[1][4]. PDRN activates adenosine A2A receptors on dermal fibroblasts, stimulating collagen type I and III synthesis and enhancing microvascular perfusion in the treated tissue ^[2][3]. Primary endpoints included dark circle severity (assessed by a validated 5-point photographic scale), periorbital wrinkle depth (measured via optical profilometry), and dermal thickness (assessed by high-frequency ultrasound dermoscopy) at baseline, 8 weeks, and 16 weeks ^[1][4][5].

Methods

Subjects were randomized 1:1 and received either PDRN or placebo via standardized micro-droplet intradermal injection in the infraorbital and lateral canthal regions ^[1][4]. Injection points were spaced 5 mm apart in a semicircular pattern following the inferior orbital rim, delivering 0.02 mL per point using a 32G needle at a depth of 1.5-2 mm ^[4]. All injections were performed by the same trained dermatologist to ensure consistency ^[1]. Dark circle severity was graded independently by two blinded assessors using a validated 5-point scale (0 = none, 4 = very severe) ^[1][4]. Wrinkle depth was quantified using Replica optical profilometry with silicone molds of the lateral canthal area ^[4]. Dermal thickness was measured at a standardized infraorbital point using 20 MHz high-frequency ultrasound ^[1][5]. Secondary endpoints included patient self-assessment of skin quality (firmness, brightness, and overall satisfaction on 10-point VAS) and adverse event documentation ^[4][5].

Results

At 16 weeks, the PDRN group demonstrated significant improvements across all primary endpoints compared to the control group ^[1][4]. Mean dark circle severity scores decreased from 2.6 to 1.6 in the PDRN group (38.4% reduction) versus 2.5 to 2.3 in the control group (8.0% reduction; between-group p<0.01) ^[1][4]. Periorbital wrinkle depth decreased by 27.6% in the PDRN group versus 5.8% in controls (p<0.05) ^[4]. High-frequency ultrasound revealed a mean dermal thickness increase of 18.2% in the PDRN group (from 0.88 mm to 1.04 mm) versus 3.4% in controls (from 0.87 mm to 0.90 mm; p<0.01) ^[1][5]. Patient satisfaction scores for skin firmness (7.8 vs 4.1, p<0.001), brightness (7.2 vs 3.9, p<0.001), and overall satisfaction (7.6 vs 4.0, p<0.001) were significantly higher in the PDRN group ^[4][5]. No serious adverse events were reported; transient ecchymosis at injection sites occurred in 14.3% of PDRN subjects and resolved within 5-7 days ^[1][4]. These outcomes are consistent with PDRN's demonstrated ability to activate A2A receptors on fibroblasts, promoting de novo collagen synthesis and VEGF-mediated microvascular improvement, both of which are critical for restoring periorbital skin thickness and reducing hyperpigmentation associated with vascular stasis ^[2][3][5].

Conclusion

This pilot study provides moderate evidence that intradermal PDRN micro-injections can meaningfully improve periorbital skin quality, including dark circle severity, fine wrinkle depth, and dermal thickness ^[1][4]. The A2A receptor-mediated mechanism supporting fibroblast activation and neocollagenesis offers a biologically plausible explanation for the observed clinical improvements ^[2][3]. PDRN's favorable safety profile in this delicate anatomical region — with no serious adverse events — supports its potential as a minimally invasive option for under-eye rejuvenation ^[1][4][5]. Larger randomized controlled trials with extended follow-up are warranted to confirm these findings and determine optimal treatment frequency and dosing for periorbital applications.