Network Meta-Analysis Ranks Best Topical Treatments for Sun-Damaged Skin

Photoaging—premature skin aging driven by cumulative ultraviolet radiation—is among the most common dermatological concerns worldwide, producing fine lines, deep wrinkles, dyspigmentation, and reduced elasticity. While sunscreen and protective clothing prevent further damage, reversing existing photodamage requires active topical intervention. The landscape of available agents is crowded and comparative evidence has been fragmented across individual trials with inconsistent outcome measures, making clinical decision-making difficult.

To address this, researchers from Sun Yat-sen University and collaborating institutions conducted a pre-registered (PROSPERO CRD42024528500) systematic review and Bayesian network meta-analysis. They searched PubMed, Embase, Web of Science, and the Cochrane Register through June 2025, ultimately including 23 RCTs enrolling 3,905 participants (average age 49.6 years; ~93% female; average treatment duration 8 weeks). Compounds evaluated included isotretinoin, tretinoin, retinol, tazarotene, adapalene, glycolic acid, and bakuchiol, each compared against placebo or each other. Outcomes spanned fine wrinkles, coarse wrinkles, skin roughness, hyperpigmentation, and adverse events. Bayesian NMA was executed using Markov chain Monte Carlo sampling (250,000 iterations), with convergence confirmed via the Brooks-Gelman-Rubin statistic and rankograms used to visualize probability distributions of relative rankings.

For fine wrinkles, isotretinoin demonstrated the strongest direct evidence (OR 116.23; 95% CI 19.08–708.19), followed by retinol (OR 14.10; 95% CI 4.80–41.38) and tazarotene (OR 3.95; 95% CI 1.41–11.10). Tretinoin also reached significance, while adapalene approached but did not achieve statistical significance. Glycolic acid and bakuchiol did not significantly improve fine wrinkles versus placebo. Tazarotene emerged as the top-ranked agent for coarse wrinkle reduction, while glycolic acid was most effective for skin roughness. For hyperpigmentation, tretinoin and retinol showed superior performance. Safety analysis revealed tretinoin carried the most favorable tolerability profile overall, whereas tazarotene and glycolic acid were associated with notably higher rates of adverse events such as irritation, redness, and dryness. Balancing efficacy across multiple outcomes with safety, isotretinoin and tretinoin were identified as the most clinically versatile options.

These findings carry meaningful practical implications for dermatologists and patients seeking evidence-based topical regimens. Retinoids as a class dominate performance across nearly every photoaging outcome, reinforcing their mechanistic role in upregulating collagen synthesis and accelerating epidermal turnover. Glycolic acid's strength in roughness reduction but weaker tolerability profile suggests it may be best suited as an adjunct rather than a primary agent. The relatively favorable safety profile of tretinoin is notable given its long clinical history and wide availability.

Several limitations temper the conclusions. The evidence base is heavily skewed toward Caucasian populations, limiting generalizability to other skin types and ethnicities. Variability in dermatological assessment scales and treatment durations (4–36 weeks) introduced heterogeneity. Potential commercial bias was noted, as a sensitivity analysis comparing academic versus industry-funded studies was conducted but sponsorship influence cannot be fully excluded. Additionally, most trials focused on single agents, leaving combination therapy strategies unaddressed.