Treatments in Periorbital Hyperpigmentation: A Systematic Review and Single-Arm Meta- Analysis of Clinical Trials

Background: Periorbital hyperpigmentation (POH) is a common cosmetic concern characterized by bilateral darkening around the eyes, impacting quality of life. Classified as pigmented, vascular, and structural. Treatments include non-invasive treatments encompass topical agents and lasers, while invasive options include fillers or surgery. Despite a standardized guideline, this study synthesizes current evidence to identify the most effective therapies, evidence-based strategies for optimal POH management. Methods: Following PRISMA guidelines and registering this review in PROSPERO (CRD420251082683), six databases were searched through June 2025 including randomized controlled trials of periorbital hyperpigmentation therapies. Primary outcomes include dermatologist assessments, pigmentation grading scales, patient-reported satisfaction and studies reporting response categories (e.g., excellent or good). Secondary outcomes will include adverse events as erythema. Random-effects models were used to calculate pooled effect sizes. Risk of bias was assessed using the Cochrane Rob 2.0 tool for randomized controlled trials (RCTs) and the ROBINS-I V2 tool for non-randomized controlled trials. Results: Thirty-one studies (n = 1,257) met inclusion criteria. Clinical improvement was assessed by dermatologist evaluation as “good” (>50%) and “excellent” (>75%). Carboxytherapy achieved the highest pooled rate of good improvement 0.50 (95% CI: 0.27 to 0.73; I² = 74.8%), and of excellent improvement 0.26 (95% CI: 0.17 to 0.37; I² = 15.3%). Carboxytherapy also was associated with notable reductions in VAS scores (4.69; 95% CI: 3.97 to 5.40; I² = 67.4%), melanin index reduction (75.23; 95% CI: 23.41 to 127.04; I² = 97.7%) and the lowest pooled value for erythema index (41.09 (95% CI: 28.58 to 53.60). For patient satisfaction carboxytherapy consistently yielded the highest rate of good satisfaction (0.52; 95% CI: 0.38–0.66; I² = 32.8%), whereas carboxytherapy (0.21, 95% CI: 0.07 to 0.47; I² = 56.4%) and PRP consistently achieved an excellent satisfaction (0.18; 95% CI: 0.11–0.28; I² = 0.00%). Conclusion: Carboxytherapy and PRP improve clinical efficacy and patient satisfaction in POH by effectively reducing pigmentation and erythema with favorable safety profiles. However, study heterogeneity and lack of standardized subtype classifications limit conclusions. Well-designed, standardized trials are essential to optimize treatment protocols and confirm the long-term safety.