Study Parameters measured Method Measurement method Skin area studied Time, w C. asiatica product Placebo/ comparatorp AEs/dropouts Zhang et al. (22) Periorbital wrinkles Photos assessed by nine dermatologists 10-point scale Crow’s feet 0 3.4 ± 1.5 3.3 ± 1.4 4 3.0 ± 1.5 3.3 ± 1.4 0.02 8 2.6 ± 1.2 3.2 ± 1.3 0.001 One dropout work- related cause 12 2.5 ± 1.2 3.3 ± 1.4 0.001 AEs, NR Visioscan VC98 SEw-value Crow’s feet 12 Increased decreased 0.05 Self-assess-ment Coarse and fi ne wrinkles Crow’s feet 12 Only fi ne wrinkles improved 0.05 * p compare intervention with placebo/comparator . **Lee et al., not clear what these numbers mean (see comments in the article). Table III Continued JOURNAL OF COSMETIC SCIENCE 448

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.