Topical 7% Ectoine Modulates Cutaneous Response During Serial Vascular 1064-nm Nd:YAG Laser Therapy: A Randomized, Vehicle-Controlled Split-Face Study

Background: Repeated vascular laser exposure induces not only selective photothermal effects within blood vessels but also secondary responses in the surrounding skin. This study investigated whether topical 7% ectoine modifies the trajectory of cutaneous response during a series of 1064-nm Nd:YAG laser treatments. Methods: Thirty participants underwent four 1064-nm Nd:YAG laser treatments in a prospective, randomized, vehicle-controlled split-face study. Following each treatment, one side of the face received a formulation containing 7% ectoine (ECT), whereas the contralateral side received an identical vehicle without ectoine (vehicle control). Skin erythema, stratum corneum hydration, transepidermal water loss (TEWL), melanin index, and skin surface pH were assessed longitudinally. Redness was independently quantified using the CIELAB a* coordinate, while high-frequency ultrasonography was used to determine the proportion of low-echogenic pixels (LEPs). An untreated internal reference area (UIRA) was additionally assessed to characterize spontaneous temporal and environmental variability in skin parameters. The study was retrospectively registered in the ISRCTN registry (ISRCTN69645337). Results: Compared with the vehicle, ECT produced a significantly greater overall reduction in skin erythema (ΔΔ = −35.44 AU; 95% CI: −44.88 to −26.01; p < 0.001), accompanied by a greater reduction in CIELAB a* (ΔΔ = −1.18; 95% CI: −1.58 to −0.78; p < 0.001). ECT was also associated with a greater overall improvement in stratum corneum hydration assessed by corneometry (ΔΔ = +5.96 AU; p < 0.001), a greater reduction in TEWL (ΔΔ = −0.73 g/m2/h; p = 0.0012), and a greater decrease in LEPs (ΔΔ = −0.55 percentage points; p < 0.001). No significant between-treatment advantage was observed for the melanin index or skin surface pH. Conclusions: Topical application of 7% ectoine during serial vascular 1064-nm Nd:YAG laser therapy was associated with a distinct trajectory of cutaneous response compared with the vehicle alone. The effect was characterized by a greater reduction in the erythematous component, improvement in barrier-related parameters, and changes in dermal echogenic properties. These short-term instrumental findings support further investigation of ectoine as an adjunctive topical strategy during repeated photothermal procedures; their clinical significance requires confirmation using standardized clinical and patient-reported outcomes.