Published in the Journal of Clinical Medicine (2026;15(13):4971, dated June 26, 2026), this narrative review by Khan and Hafeez synthesizes hyaluronic acid filler versus polynucleotide (PDRN) evidence for the under-eye and periorbital region, anchored on head-to-head split-face RCT data (Lee et al., a randomized double-blind split-face periocular trial). Narrative review means directional, not definitive, so read it as a framework rather than a verdict.

The framing is about matching tool to problem. HA fillers remain the standard for true volumetric tear-trough correction, but they carry real risks in thin periorbital skin: the bluish Tyndall effect and malar edema. Polynucleotides work differently, as bioactive agents that drive dermal remodeling, angiogenesis, and an anti-inflammatory response, improving elasticity, hydration, and fine wrinkles without adding volume, with a favorable safety profile. The underlying split-face RCT found GAIS and VAS parity between the two, but polynucleotides came out superior on objective biometric skin-quality metrics: elasticity, hydration, roughness, and pore volume. The authors are candid that the evidence is heterogeneous, with no standardized protocols and few large comparative trials.

The practical read: stop reaching for HA filler reflexively under the eye. A true hollow that needs volume still goes to HA. But for crepey, dehydrated, poor-quality under-eye skin, or a patient prone to puffiness and malar edema, choose polynucleotides, or lead with PN before any HA. You buy skin-quality improvement with markedly lower Tyndall and edema risk in a zone that punishes mistakes.

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