A critical evidence review published June 26, 2026 in the Journal of Clinical Medicine compares polynucleotides (PN, particularly PDRN) against HA fillers for under-eye and tear-trough rejuvenation, and lands on a case-selection rule rather than a winner. HA remains the gold standard for volumetric correction, but its limits in skin quality and its risks, the Tyndall effect and malar oedema, are what drive interest in regenerative alternatives. Polynucleotides show consistent gains in dermal quality, elasticity, hydration and fine rhytids, through dermal remodelling, angiogenesis and an anti-inflammatory effect.

The review flags the periorbital area as one of the most challenging sites in aesthetic medicine, given thin dermis, complex vascularity and a tendency toward oedema and contour irregularity. The operator takeaway is to select by goal: a true volume deficit favors HA, while poor skin quality, dark circles, or very thin skin favor PN or a combination protocol. Useful framing for the next under-eye consult where the patient wants filler but the tissue does not.

Source: Journal of Clinical Medicine (MDPI) — https://www.mdpi.com/2077-0383/15/13/4971