EFFICACY AND SAFETY OF CENTELLA ASIATICA 449 and number of wrinkles were reduced, the lipstick “bleeding” also improved signifi cantly (Table III). P ERIOCULAR WRINKLES W e performed NMA on the three studies that compared C. asiatica with placebo. Peri- ocular wrinkles below the eye and lateral canthal rhytids (crow’s feet) were assessed using the Rao–Goldman fi ve-point visual scoring scale (RG5VSS) and cutaneous topography using Visioscan imaging. C. asiatica reduced the MD measured by RG5VSS in crow’s feet wrinkles compared with P. mirifi ca at w 8 and 12 by 0.02 (95% CI: -0.03, -0.01) and 0.04 (95% CI: -0.05, -0.03), respectively (Figure 2). C. asiatica reduced MD measured by RG5VSS in under eye wrinkles compared with P. mirifi ca at w 8 and 12 by 0.02 (95% CI: -0.02, -0.01) and 0.02 (95% CI: -0.04, -0.001), respectively (Figure 3). C. asiatica reduced MD measured by Visioscan in crow’s feet wrinkles comparing vehicle at w 4, 8, and 12 by 0.4 (95% CI: -0.4, -0.4), 0.7 (95% CI: -0.77, -0.63), and 0.9 (95% CI: -0.97, -0.83), respectively (Figure 4). C. asiatica reduced MD measured by Visioscan in under eye wrinkle at w 4 and 8 compared with tretinoin by 0.04 (95% CI: -0.06, -0.02) and 0.3 (95% CI: -0.36, -0.24), respectively. When comparing P. mirifi ca at w 4 and 12 C. asiatica reduced MD by 0.46 (95% CI: -0.54, -0.38) and 0.84 (95% CI: -1.26, -0.42), respectively (Figure 5). Figure 2. Lateral angle ( crow’s feet) wrinkles measured by the RG5VSS.

JOURNAL OF COSMETIC SCIENCE 450 PARTICIPANT OPINION/SATIS FACTION All studies sought partic ipant opinions about the treatment, but no meaningful detail about these was reported. ADVERSE EVENTS One study performed a pre trial 48-h skin patch test which produced no skin reactions (20) but reported AEs (erythema, burning, pain, or dryness) during the trial. C. asiatica treatment yielded 10 AEs compared with 35 cases with tretinoin, 18 at 4 w, 12 at 8 w, and fi ve at 12 w (Table III). However, another study using a similar protocol and identical C. asiatica formulation reported no AEs. None of the AE reports had severity ratings. Other studies either did not mention AEs or specifi cally stated that no AEs were found. Trials suffered some dropouts: Lee et al. (18) lost two participants, and Tangsumroeng- wong (20) had three dropouts, but reason(s) for leaving were not reported. The dropout in Zhang et al. (22) had other commitments. ADHERENCE TO TREATMENT. N o study reported on adhe rence to treatment. Figure 3. Under-eye wrinkl e s measured by the RG5VSS.