A Comparative Study of Two Topical Treatments for Photoaging of the Hands

Abstract

Background:

Multiple effective treatments exist for correction of skin photoaging. Topical L-ascorbic acid (vitamin C), a well-known antioxidant and topical human platelet extract (HPE), is a novel off-the-shelf cosmetic ingredient that has shown positive results in recent clinical studies. HPE is a leukocyte-depleted allogeneic product derived from United States–sourced, pooled, apheresed platelets produced with consistent batch quality, purity, and effect. The authors sought to characterize the effect of topical HPE (plated) intense serum (Rion Aesthetics) compared with vitamin C (C E Ferulic with 15% L-ascorbic acid; SkinCeuticals) in skin rejuvenation of dorsal hands after 12 to 26 weeks of twice-daily use.

Methods:

This prospective, longitudinal study sought to compare the effectiveness of 2 known treatments for skin rejuvenation. Evaluations at baseline and 6, 12, and 26 weeks included photographic documentation to assess common skin concerns related to aging.

Results:

For age-related skin appearance on the dorsal hands, topical HPE was noninferior to topical vitamin C for improvement in brown spot fractional area, wrinkle fractional area, and improvement in luminosity at 12 weeks after twice-daily topical use.

Conclusions:

HPE performed as well as vitamin C to rejuvenate the skin on the dorsal hands after 12 to 26 weeks of twice-daily topical use. Both topical serums may yield similar or superior results versus invasive procedures, such as intense pulsed light, in reducing brown spots on the dorsal hands. These topical products work equally well in both sexes. Skin improvements lasted through 6 months.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.

Topical skin-rejuvenating treatments traditionally have focused on the face; other visible parts of the body, particularly the hands, have largely been neglected. As we age, multiple aesthetic aspects of the dorsum of the hand are affected, including dermal thinning¹ and the prominence of veins, tendons, and bony contours.^2,3 The hands are highly susceptible to ultraviolet light exposure, leading to photoaging and changes in cutaneous pigmentation.¹

Recent literature has suggested that hand appearance affects perceived age.⁴ The appearance of the hands is the second most telling sign of chronologic age, second only to the face,⁵ leading patients to seek treatments that restore a more youthful appearance of the hands. As patient requests for hand rejuvenation have become frequent, many companies have sought to develop aesthetic products specific to hand volume restoration, validate aesthetic scales to measure hand volume deficiency,^6–9 and conduct clinical trials of products for hand volumization.^10–14 Although a variety of invasive treatments are available, topical products that improve manifestations of aging hands are needed.¹⁵

Options for cutaneous hand rejuvenation include antioxidants, chemical peels, microdermabrasion, intense pulsed light (IPL), laser therapy, ablative resurfacing, and topical products.⁵ Soft-tissue atrophy of the aging hand is commonly treated with dermal fillers or fat augmentation.^16,17 Injectables with US marketing approval for correction of hand volume deficit include hyaluronic acid dermal filler, Restylane Lyft (Galderma), and the calcium hydroxyapatite biostimulator Radiesse (Merz).^18,19

Human platelet extract (HPE) has received tremendous attention in antiaging skin rejuvenation.²⁰ HPE is a novel topical product derived from United States–sourced, leukocyte-reduced apheresed platelets.²¹ In a recent clinical study, topical HPE demonstrated quantifiable and statistically significant improvements in overall skin appearance when used topically twice daily on facial skin.²¹

SkinCeuticals C E Ferulic (L’Oréal) vitamin C serum is formulated with a combination of antioxidants, including 15% pure vitamin C, 1% vitamin E, and 0.5% ferulic acid. It has been shown in studies to help brighten the skin, reduce pigmentation, and stimulate collagen to help reduce signs of skin aging.^22–24

This study sought to compare 2 topical treatments for photoaging of the hands. We examined evidence-based outcomes for skin rejuvenation on the dorsal hands using HPE versus vitamin C in a topical cosmetic application after 12 to 26 weeks of continuous twice-daily use.

PATIENTS AND METHODS

This prospective, single-center, longitudinal study was conducted in accordance with the International Conference on Harmonization, Good Clinical Practice guidelines, Code of Federal Regulations, and the Declaration of Helsinki. The Mayo Clinic institutional review board approved the study. All participants gave informed consent before any study procedures were performed. This study has been discussed with the US Food and Drug Administration Center for Biologics Evaluation and Research. Future studies evaluating medical indications or skin health measures will be pursued under Food and Drug Administration investigational new drug application.

The target population for inclusion was men and women 40 to 85 years of age with moderate photoaging who were not pregnant or nursing, agreed to comply with the study protocol, and were willing to discontinue any other antiaging treatments for the duration of the study. The study aimed to recruit participants across all Fitzpatrick skin phototypes. Primary exclusion criteria included aesthetic or antiaging treatments during the past 6 months, such as dermal fillers, peels, plastic surgery, platelet-rich plasma, or other treatments that could change the skin’s surface. Individuals with dermatologic disease, cutaneous marks on the planned treatment area, skin hyperreactivity, treatment with prescription-strength vitamin A within the past 3 months, treatment with topical steroids on the treatment area within the past 16 days, or a previously observed allergy to colophony, nickel, or food or cosmetic products were excluded. Individuals who met all inclusion criteria and no exclusion criteria were enrolled.

Topical HPE is generated from United States–sourced, leukocyte-depleted apheresis platelets. Platelet-derived extracellular vesicles comprising HPE are characterized based on their antioxidant activity using an activity assay. All HPE lots must meet a preset requirement for this antioxidant activity before release of the product. Product pricing varies; topical HPE (plated) intense serum (Rion Aesthetics) ranges between $240 and $280 and vitamin C (C E Ferulic with 15% L-ascorbic acid; SkinCeuticals) ranges between $160 and $190.

Participants followed a standardized skin care routine for 12 to 26 weeks that included twice-daily topical applications of HPE to the right dorsal hand and twice-daily applications of vitamin C to the left dorsal hand. Clinical evaluations were conducted on day 0 (baseline) and weeks 6, 12, and 26, including standardized imaging (Canfield VISIA-CR generation 5 with 3-dimesional [3D] viewer [PRIMOS] to evaluate targeted fluorescence imaging of protoporphyrin IX and coproporphyrin III for measuring microbial activity, standard white light, and polarized imaging for textural and topographic information); RBX red/brown processing for measuring pigmentation, redness, and brown spot pixel variation; and 3D imaging with PRIMOS for performing roughness and volumetric measurements. Measures included wrinkle fractional area, erythema fractional area, brown spot fractional area, luminosity score, and color evenness. Wrinkles were assessed using 3D fringe projection to evaluate static wrinkles and measure the difference in fractional area between time points. RBX technique was applied for the erythema fractional area, and the cross-polarized image was transformed into red images correlated with hemoglobin absorption and distribution. Brown spots, color evenness, and color intensity (luminosity) were measured by assessing overall variation in color values, specifically pixel variation, across defined cosmetic subunits, and how rapidly those colors change spatially within them.

The primary goal included evaluation of effectiveness of the topical study products, including the change in photoaging scores from baseline to 12 or 26 weeks using the Canfield VISIA system.

Statistical Analysis

The change from baseline to 12 or 26 weeks was compared across treatments using 1-sided t tests with a 10% noninferiority margin. Differences from baseline at 6, 12, and 26 weeks are reported with 95% CIs for each treatment. Fisher exact test of equal proportions was also used.

Our analysis treated each hand as independent. This is justified by the nonrandomized study design and the known differences in exposures between hands (eg, in golfers who wear a single glove). Because this study used 2 treatments—one applied to the participant’s left hand, and one to the right hand—we first demonstrated no difference between the left and right hands at baseline using t tests with no correction for multiple tests, finding no significant differences between average results from the left and right hands. Therefore, we continued to analyze the differences in outcomes over time based on the assumption of no baseline differences. JMP Pro 17.1 (JMP Statistical Discovery) was used for statistical analysis.

RESULTS

Sixty participants (52 female, 8 male; age range, 40 to 80 years; mean, 52.5 years) with moderate photoaging were consented and enrolled in the study and followed up for up to 26 weeks. One participant did not continue after baseline, and 4 participants discontinued the study before week 6; 55 participants continued to week 12; and 28 participants remained in the study for 26 weeks. Most participants were Fitzpatrick skin phototype II (83.3%), with 8.3% type III, 6.7% type IV, 1 type V, and no type I or VI. The study was conducted at a single center (Mayo Clinic).

In dorsal hand skin, topical HPE was noninferior to vitamin C for improvement in brown spot fractional area, wrinkle fractional area, and improvement in luminosity at 12 weeks after twice-daily use. The products had similar results for color evenness. The average percentage change from baseline summary statistics within treatment group for all 5 observed measures is depicted in Table 1. The 95% CIs for the percentage change from baseline for all observed measures for each product overlapped at each time point, supporting equivalent performance of the 2 topical cosmetic products.

Table 1.

Average Percentage Change from Baseline Summary Statistics within Treatment Group

Area	Time Point	Average % Change from Baseline		Difference, HPE – Vit C	95% CI for Difference in % Change from Baseline
		HPE	Vit C		LCL	UCL
Brown spot fractional area	6 weeks	−4.1	−8.5	4.4	−3.1	11.9
	12 weeks	−27.4	−32.3	4.9	−0.01	10.4
	26 weeks	−23.4	−26.1	2.7	−7.5	12.8
Color intensity	6 weeks	7.5	7.0	0.5	−1.4	2.6
	12 weeks	11.3	11.7	−0.4	−3.2	2.5
	26 weeks	4.5	5.0	−0.5	−4.3	3.3
Color evenness	6 weeks	5.2	6.8	−1.6	−11.1	7.8
	12 weeks	12.7	17.6	−4.9	−15.7	5.8
	26 weeks	3.3	6.9	−3.6	−11.6	4.2
Wrinkle fractional area	6 weeks	−10.9	−14.8	3.9	−2.7	10.6
	12 weeks	−16.9	−14.8	−2.11	−7.4	3.2
	26 weeks	−12.9	−14.4	1.5	−9.4	12.4

HPE, human platelet extract; LCL, lower control limit; UCL, upper control limit; Vit C, vitamin C serum.

Brown spot fractional area and wrinkle fractional area both decrease with improvement in aging skin. In this study, we observed a reduction (improvement in skin appearance) in brown spot fractional area over time for both products (Fig. 1). The most considerable difference from baseline was observed at 12 weeks, and that change was maintained through 26 weeks in the subset of participants (n = 28) who remained in the study through week 26. For the brown spot fractional area, the average percentage change from baseline at each time point was slightly better for improvement in the vitamin C group; however, it was not statistically significant. A 10% noninferiority margin at 12 weeks demonstrated that HPE was noninferior to vitamin C (P = 0.0336). The difference in percentage change was 0.05% (27% versus 32%).

Fig. 1.

Percentage change from baseline improvement (95% CI) in brown spot fractional area for HPE compared with intense pulsed light as measured with Canfield VISIA RBX technology.

For the wrinkle fractional area, the most considerable difference from baseline was observed at 12 weeks. The change was maintained through 26 weeks in the subset of participants who remained in the study. A 10% noninferiority margin at 12 weeks demonstrated that HPE was noninferior to vitamin C for the wrinkle fractional area (P < 0.0001). The difference in percentage change was 0.02% (17% versus 15%).

Color intensity/luminosity and color evenness both increase with improvement in skin aging. We observed a similar increase in both products over time. For luminosity, there was no difference between products at week 12; therefore, HPE was noninferior to vitamin C (P < 0.0001) with a difference in percentage change of 0.003 (11.3% versus 11.6%). There was a slightly larger improvement with vitamin C over HPE in terms of color evenness at week 12, with a difference of 12.7% versus 17.6%. However, the 95% CIs for the percentage change from baseline for both products overlapped at each time point.

For erythema fractional area, the percentage change from baseline analysis shows no difference in treatment. Both treatments show an average increase in redness; however, the CIs on the percentage change are very wide and include 0. This supports no change in redness in either group. At 12 weeks, Fisher exact test of equal proportions across treatments supports no difference between treatments (P = 0.2290).

The study included 8 men; 5 to 8 men had results at each time point, and the general trends were similar between sexes.

The products were well tolerated and had no reported side effects (Figs. 2 and 3). No participant experienced pain, irritation, or swelling when using the products on the dorsal hand.

Fig. 2.

Before and after photographs of the right dorsal hand (above row) of a 59-year-old woman treated with HPE twice daily for 6 months and the left dorsal hand (below row) treated with vitamin C twice daily.

Fig. 3.

Before and after photographs of the right dorsal hand (above row) of a 55-year-old woman treated with HPE twice daily for 6 months and the left dorsal hand (below row) treated with vitamin C twice daily.

DISCUSSION

Vitamin C and HPE work in different ways but are both effective treatments for skin rejuvenation. HPE has several abilities beneficial for skin rejuvenation (angiogenic ability, collagen synthesis, and regulation of inflammation),²⁵ whereas vitamin C acts as an antioxidant agent and free radical seeker that can protect cells from oxidative stress.²⁶ However, when used regularly as part of a skin care routine, both products in a topical serum reduce signs of photoaging, such as brown spots, wrinkles, and erythema, while brightening and evening skin tone. Before and after photographs of 2 women who were treated with HPE on the right hand and vitamin C on the left hand for 26 weeks are included in Figures 2 and 3.

The rationale for topical use of HPE versus vitamin C is predicated on the fact that a key release step for HPE is based on its antioxidant activity. Furthermore, the effects of platelet-derived extracellular vesicles on soft-tissue regeneration have been explored extensively by our team, with results suggesting additional putative modes of action that may be contributory.^27–29

Compared with published results of IPL as a treatment for benign pigmented lesions on the dorsal hands, both topical products performed better, with an improvement in brown spot fractional area using the same technique for measurement (Canfield VISIA RBX). In this study, topical HPE demonstrated a 27% reduction in brown spots at week 12 (Fig. 1). A study using a similar imaging analysis (VISIA Complexion Analysis System; Canfield Scientific) found 7.52% reduction in brown spots at week 4 in participants receiving 3 monthly IPL treatments.³⁰

Study limitations included a small number of men, few darker skin types (8% Fitzpatrick IV or V, 0 type VI), and only 50% of the total sample size completing the study from 12 to 26 weeks. In addition, the study design as a nonblinded and nonrandomized assessment of 2 topical agents for reversing age-related changes is a limitation. Future studies can be designed to reduce bias with blinding, randomization, and additional control with an agent without antioxidant effects.

CONCLUSIONS

HPE performed as well as vitamin C to rejuvenate the skin on the dorsal hands. Both topical serums could serve as an adjuvant or preprocedure primer to invasive procedures, such as IPL, in reducing brown spots. The cosmetic products work equally well in men and women. Additional randomized controlled studies should be conducted to determine whether a synergistic relationship exists between topical vitamin C and HPE, if used in combination.

DISCLOSURE

Dr. Wyles and L. E. Jankov are consultants for Rion Aesthetics, LLC. Dr. Paradise is an employee of Rion, Inc. Dr. Behfar and Mayo Clinic have ownership interest in Rion, Inc., and Rion Aesthetics, LLC. Dr. Copeland and Dr. Bucky have no financial interests to disclose. This study was financed in part by Rion Aesthetics, LLC.