Regenerative and Multimodal Approaches for Periorbital Hyperpigmentation: A Clinical Review of Emerging Therapies

Periorbital hyperpigmentation (POH) is a common aesthetic concern that contributes to a fatigued or aged appearance. Multifactorial in origin, POH may involve dermal melanin deposition, vascular congestion, structural hollowness, or thin periorbital skin. Conventional therapies such as topical lightening agents, chemical peels, and lasers provide limited efficacy, particularly in mixed etiology cases. This review evaluates eight recent clinical studies exploring novel interventions, including stromal vascular fraction (SVF), platelet-rich plasma (PRP), nanofat, biofiller, mesotherapy, nonablative lasers, microneedling, and peptide-based topicals. Interventions ranged from injectables and laser treatments to combination topical formulations. Outcomes were assessed by clinical grading scales, instrument-based analysis, and patient-reported improvements. The highest pigmentation reductions were observed in combination therapies, especially those involving autologous regenerative products such as SVF, nanofat, and PRP. Non-invasive modalities such as botanical peptide creams and fractional lasers also demonstrated benefits such as improving hydration and dermal texture. All treatments were well tolerated, with few adverse effects reported. However, limitations across studies included small sample sizes, short follow-up durations, and lack of standardized outcome measures. These findings support a shift toward multimodal and individualized treatment strategies for POH, but additional high-quality trials with standardized metrics are needed to inform clinical practice.