1 INTRODUCTION

The skin is the largest and most visible organ of the human body with important protective and regulatory functions. The epidermal barrier forms the first line of defense against exogenic factors and pathogenic microorganisms. The skin also plays an important role in thermoregulation, metabolic processes, and sensory perception.1-3 Adjacent to its function, skin plays a key role in aesthetics; unfortunately, skin quality decreases over time due to aging, especially in the face. Facial aging is characterized by many changes in a broad spectrum of facial skin features, for example, pigmentation, wrinkles, and rosacea.4, 5 Aging of skin can be categorized into two types of aging: intrinsic and extrinsic aging. Intrinsic aging derives from genetic and hormonal influences, whereas extrinsic aging is caused by environmental factors, such as cigarette smoke, ultraviolet radiation, or trauma.4, 6 In the epidermis of the skin, aging of the face is characterized by loss of dermal mast cells and fibroblasts as well as by shortening of telomeres. In the dermis, lower levels of collagen, dysfunctional collagen, and a reduction of elastin fibers are observed.4 These cellular changes result in increased pigmentation, loss of elasticity, and formation of wrinkles over time.5, 7

Nowadays, people have become progressively concerned about their aged facial skin features. Many autologous treatments, for example, lipofilling, platelet-rich plasma, or nanofat, aim to either slow down or reverse these visible signs of skin aging and thereby improving skin quality.8 Generally, skin quality and skin quality improvement is assessed merely by visual inspection by the patient and practitioner, which is accompanied by disadvantages of interperson variability and recall-bias, making the results rather unreliable. Some clinicians determine the effectiveness of such interventions by assessing skin quality with the use of a measurement tool as, for example, tristimulus colorimetry to measure skin color, the Cutometer or Ballistometer for skin elasticity, and polarization imaging techniques to assess skin texture.9-11 However, it remains unknown whether these devices are accurate and dependable. Therefore, the aim of this study is to systematically search for the best-validated medical devices to assess skin quality (i.e., skin color, texture, and elasticity) in the most reliable way.

2 METHODS 2.1 Protocol, information sources, and search

This systematic review was performed according to the PRISMA statement.12 The databases MEDLINE, Embase, Cochrane Central, Web of Science, and Google Scholar were searched on April 16, 2019. An update search was performed on December 15, 2020. The detailed search strategy is provided in the Supplementary Content (S1).

2.2 Eligibility criteria and study selection

Title and abstract were independently screened by two authors (M.L. and L.v.d.L.) using eligibility criteria. Full article studies were included if studies investigated the reliability and validity of medical devices assessing changes in human “ordinary” aged skin, that is, skin color, texture, or elasticity (Table 1). Studies were included if reported at least one of the following items regarding skin quality measurement devices: intraobserver reliability, interobserver reliability, interinstrument reliability, or construct validity. Studies evaluating content and criterion validity were not found. Studies assessing the quality of “diseased” skin, for example, melanoma, scars, or burn wounds, were excluded as well as animal studies. Reference lists of included studies were hand-searched for relevant studies. Disagreements were discussed during a consensus meeting with the last author (J.v.D.).

TABLE 1. Inclusion and exclusion criteria Inclusion criteria Exclusion criteria Human skin Diseases and trauma affecting skin quality, for example, burn wounds, scars, and disease-caused Medical devices assessing human skin texture, color, or elasticity Reporting of intraobserver and/or interobserver reliability and/or interinstrument observer reliability and/or validity Prospective and retrospective studies Case reports, conference abstracts, letter to the editor, and reviews 2.3 Assessment of quality of included studies and risk of bias

The included studies were graded on quality of evidence using the Oxford Center for Evidence-Based Medicine (OCEBM) criteria.13 Disclosure agreements and funding status were reviewed for each study.

2.4 Data extraction

Measurement devices were scored on reporting construct validity by means of convergent validity and inter or intraobserver as well as interinstrument reliability. For construct validity, the Pearson's correlation coefficients of correlations between measurement devices were extracted and the median was depicted in a correlogram. Correlations > 0.5 or < −0.5 were considered strong. For reliability, intraclass correlation coefficients (ICCs) were reported. ICCs > 0.8 were considered good, moderate between 0.6 and 0.8, and poor < 0.6.

3 RESULTS 3.1 Included studies

The initial search identified 3724 publications (Figure 1). The update search yielded 621 additional publications. Hand-searching reference lists of included publications identified two additional records. After abstract screening, 4296 were excluded. Fifty studies were read in full text and assessed on eligibility criteria. Twenty-seven studies did not describe an outcome of interest and were excluded. Four publications were reviews and therefore excluded. One publication was excluded because of evaluating diseased skin. One study was excluded as it was a letter to the editor. Following full-text assessment, 18 publications were included in this systematic review.9, 10, 14-29

Flow diagram of study selection

3.2 Study characteristics 3.2.1 Skin color

Eleven studies assessed skin color describing a total of 16 different measurement devices analyzing 3172 subjects (Table 2).9, 14-22, 25, 30 The largest study by Uter et al. accounted for 2287 of included subjects.9 All studies evaluated measurement devices in a predominantly Caucasian population, except for one study by Wright et al.14 Wright et al. researched the DRS probe and Mexameter MX 18 in a predominantly (68.5%) African American population (n = 503).14

TABLE 2. Study characteristics of studies on skin color measurement Author, year Population (n) Device Principle Clinical parameter Measurement region Intervention Measurement timings Repetitive measurements (n) Wright et al., 2016

503

African American

DRS Probe

Mexameter MX 18

Diffuse reflectance spectroscopy

Narrow-band reflectance spectrophotometry

Melanin, erythema

Melanin, erythema

Inner part of upper arm

Inner part of upper arm

–

Baseline

Baseline

3

3

Matias et al., 2015 30

Antera 3D

Mexameter MX 18

Colorimeter CL-400

Reflectance mapping with L*a*b* color system

Narrow-band reflectance spectrophotometry

Tristimulus colorimetry with L*a*b* color system

Melanin, erythema, skin color

Melanin, erythema

Skin color

The back

The back

The back

UVB light exposure at various intensities

UVB light exposure at various intensities

UVB light exposure at various intensities

Baseline, 2, 7, 12, and 14 days

Baseline, 2, 7, 12, and 14 days

Baseline, 2, 7, 12, and 14 days

5

5

5

Baquie and Kasraee, 2014 12

Dermacatch

Mexameter MX 16

Visible-spectrum reflectance colorimeter

Narrow-band reflectance

spectrophotometry

Melanin, erythema

Melanin, erythema

Volar side of the forearm and the back

Volar side of the forearm and the back

UVB light exposure, methyl nicotine cream or dermocorticoid cream

UVB light exposure, methyl nicotine cream or dermocorticoid cream

Baseline, 2, 7, and 14 days

Baseline, 2, 7, and 14 days

10

10

Hua et al., 2014 20

“Soft Plus” with melanin probe

Mexameter MX 18

Double wavelength reflectance

photometry

Narrow-band

spectrophotometry

Melanin

Melanin

Face

Face

–

Baseline

Baseline

3-5

3–5

Gankande et al., 2014 30 DermaLab Combo Narrow-band reflectance spectrophotometry Melanin, erythema Head, neck, chest, back, arm, leg – Baseline 3 Uter et al., 2013 2287

Minolta Chromameter CR-300

Reflektometer RM 100

Tristimulus colorimetry with Yxy color system

Remission photometry

Skin color

Skin reflectance

Inner part of upper arm

Inner part of upper arm

–

Baseline

Baseline

3

3

Van der Wal et al., 2013 50

Mexameter MX 18

Colorimeter CL-400

DSM II ColorMeter

Narrow-band reflectance

spectrophotometry

Tristimulus colorimetry with L*a*b* color system

Narrow-band reflectance

spectrophotometry

and tristimulus colorimetry with L*a*b* color system

Melanin, erythema

Skin color

Skin color,

erythema melanin

Trunk, upper and lower extremities

Trunk, upper and lower extremities

Trunk, upper and lower extremities

–

Baseline

Baseline

Baseline

2

2

2

Bailey et al., 2012 88 Chromometer Principle not mentioned Pigmentation Forehead, midcheek, jawline, neck, and abdomen – Baseline – Barel et al., 2001 12

Visi-Chroma VC-100

Minolta Chromameter CR-200

Tristimulus colorimetry with L*a*b* color system

Tristimulus colorimetry with L*a*b* color system

Skin color

Skin color

–

–

DHA 5% cream, methyl nicotine cream or sodium lauryl sulfate exposure

DHA 5% cream, methyl nicotine cream or sodium lauryl sulfate exposure

Baseline, 2, 4, and 24 h

Baseline, 2, 4, and 24 h

10

10

Kerckhove et al., 2001 60 Minolta Chromameter CR-300 Tristimulus colorimetry with L*a*b* color system Skin color Ventral side of the forearm – Baseline, 7 days – Shriver et al., 2000 80

Photovolt ColorWalk colorimeter

DermaSpectrometer

Tristimulus colorimetry

Narrow-band reflectance

spectrophotometry

Skin color with L*a*b*

color system

Melanin, erythema

Inner part of the upper arm, forehead

Inner part of the upper arm, forehead

–

Baseline

Baseline

3

3

L*a*b* = Commision International d'Eclairage (CIE) color system. Colors are represented by three variables: L*, the lightness-darkness axis; a* the red-green axis; and b*, the blue-yellow axis. Yxy = Commision International d'Eclairage (CIE) color system. Y value represents lightness-darkness axis. DHA = dihydroxyacetone, product used for tanning of the skin.

The two most frequently employed techniques were narrow-band reflectance spectrophotometry and tristimulus colorimetry. In narrow-band reflectance spectrophotometry, differences in red and near infrared light absorption and reflection of hemoglobin and melanin are used to measure vascularization (erythema) and pigmentation (melanin) of the skin.28, 31 Included devices using reflectance spectrophotometry to assess skin color were the Mexameter MX 16 and 18, DermaLab Combo, DSM II ColorMeter, and DermaSpectrometer.14-19, 22 In Tristimulus colorimetry, white LED is scattered in all directions and the reflected light is measured by the probe. The reflected light is analyzed and expressed in the L*a*b* color system and Individual Typology Angle index values (ITA). L* expresses brightness on the black-white axis, a* expresses erythema values on the red-green axis, and b* gives the color position on the blue-yellow axis.15 Instruments using Tristimulus colorimetry to measure skin color are the Minolta Chromameter CR-200 and CR-300, Colorimeter CL-400, PhotoVolt ColorWalk Colorimeter, and Visi-Chroma VC-100.9, 15, 19-21

3.2.2 Skin elasticity

For skin elasticity, seven studies assessed nine types of measurement devices analyzing 290 subjects in total (Table 3).10, 17, 23-26 The Cutometer SEM 575 and Cutometer MPA 580 were the most frequently used devices and were assessed in four studies.10, 17, 24, 26 The Cutometer MPA 580 is currently still available for purchase, while the Cutometer SEM 575 has been discontinued. The Cutometer uses a suction and optical measuring system to measure various parameters, such as skin distensibility (R0), gross elasticity (R2), and skin firmness (R7).26 Xu et al. assessed the 3D-DIC, which measures the displacement of skin and minor as well as major strain of skin deformation using unidirectional force.24 Other measurement devices include the BTC-2000, which measures elastic deformation of skin under subatmospheric pressure, and the Ballistometer BLS780, which uses an impact and indentation measuring system.10, 25 Peperkamp et al. evaluated the Dermalab Combo to measure skin elasticity through suction.23 Hua et al. assessed the Soft Plus with an elasticity probe, which also measures skin elasticity by measuring stress under suction application.17 Lastly, in a single study, elastography with the Toshiba iAplio 900 was used to measure skin elasticity by measuring the velocity of ultrasonic waves through skin tissue.29

TABLE 3. Study characteristics of studies on skin elasticity measurement Author, year Population (n) Device Principle Clinical parameter Measurement region Measurement timings Repetitive measurements (n) Peperkamp et al., 2019 49 DermaLab Combo Vertical suction

ViscoElasticity (VE), Young's elasticity modulus (E), and skin retrac-

tion time (R)

ViscoElasticity (VE), Young's elasticity modulus (E), and skin retrac-

tion time (R)

Viscoelasticity (VE), Young's elasticity modulus (E), skin retraction time (R)

Six locations on arm Baseline, 45 min 2 Xu et al., 2019 12

3D-DIC

Cutometer MPA 580

Deformation of skin under unidirectional force

Suction and optical measuring system

Displacement of skin, minor strain, major strain

Net elasticity (R5),

skin firmness (R7), total recovery (R8)

Volar forearm

Volar forearm

Baseline

Baseline

3

3

Paluch et al., 2020 57 Toshiba iAplio 900 Ultrasonograph Shear wave elastography Tissue strain measured by velocity of ultrasonic wave propagation Face Baseline 3 Hua et al., 2014 20

“Soft Plus” with elasticity probe

Cutometer MPA 580

Stress/deformation of skin by suction application

Suction and optical measuring system

Elasticity

Skin distensibility (R0)

Face

Face

Baseline

Baseline

3

3

Woo et al., 2014 20

Cutometer MPA 580

Ballistometer BLS780

Suction and optical measuring system

Impact and indentation measuring system

Skin distensibility (R0), return to original skin (R1), gross elasticity (R2), last maximal amplitude (R3), last minimal amplitude (R4), net elasticity (R5),

viscoelasticity (R6), skin firmness (R7), total recovery (R8)

Firmness and elasticity

Forehead, cheek, and volar forearm

Forehead, cheek, and volar forearm

Baseline

Baseline

3

3

Bailey et al., 2012 88 BTC-2000 Deformation of skin under subatmospheric pressure Elastic deformation and stiffness Forehead, midcheek, jowl, neck, and abdomen Baseline – Ahn et al., 2007 44

Cutometer SEM 575

Moiré topography image

Suction and optical measuring system

Visual evaluation of digital contour lines (scale 1–5)

Skin distensibility (R0), gross elasticity (R2), net elasticity (R5), viscoelasticity (R6), skin firmness (R7), total recovery (R8)

Contour lines

Cheek

Cheek

Baseline

Baseline

–

–

3.2.3 Skin texture

Skin texture was assessed in two studies evaluating 72 subjects using three different types of measurement devices: the Visioscan VC 98, the PRIMOS, and the PRIMOSlite (Table 4).11, 27, 28 The PRIMOS and PRIMOSlite devices use rapid in vivo evaluation of the skin (PRIMOS) to measure surface roughness. This technique is based on the deflection of projected parallel stripe patterns on the skin due to differences in skin surface profile. The Visioscan VC 98 is a UVA-light camera that measures roughness with the Surface Evaluation for Living Skin method (SELS). The PRIMOSlite is a portable version of the PRIMOS.

TABLE 4. Study characteristics of studies on skin texture measurement Author, year Population (n) Device Principle Clinical parameter Measurement region Intervention Measurement timings Repetitive measurements (n) Kottner et al., 2012 12

Visioscan VC 98

PRIMOSlite

Phaseshift rapid evaluation

Phaseshift rapid evaluation

Surface roughness

Surface roughness

Volar forearm

Volar forearm

–

Baseline

Baseline

3

3

Bloemen et al., 2011 60 PRIMOS Phaseshift rapid evaluation Surface roughness Trunk, arm, leg, or head – Baseline 2 3.3 Reliability 3.3.1 Skin color

Interobserver reliability was highest for the Minolta Chromameter CR-300 (Table 5). Van den Kerckhove et al. reported intraclass coefficients between 0.92 and 0.99 in 60 patients with measurements provided by two independent observers.21 Both Van den Kerckhove et al. and Uter et al. reported good intraobserver reliability for the Minolta Chromameter as well (ICC 0.98–0.99 and 0.926–0.954, respectively).9, 21 Intraobserver reliability for the Reflektometer RM 100 was good in a large cohort of 2287 subjects (ICC 0.938–0.946).9 In a single study of 50 participants, Van der Wal et al. assessed the interobserver reliability of the Mexameter MX 18, Colorimeter CL-400, and DSM II ColorMeter.19 The Mexameter MX 18 and DSM II ColorMeter achieved good interobserver reliability (ICC 0.92–0.94 and 0.89–0.96, respectively). The Colorimeter CL-400 achieved moderate to good interobserver reliability (ICC 0.79–0.97).32 Gankande et al. reported interobserver reliability of the DermaLab Combo assessing both melanin and erythema. ICCs for erythema were poor to moderate (ICC 0.54–0.73) and good for melanin (ICC 0.91–0.95).18 Intraobserver reliability was not tested for the Mexameter MX 18, DSM II ColorMeter, ColoriMeter CL-400, and DermaLab Combo.

TABLE 5. Reliability of assessed devices Reliability Author, year Device Intraobserver (ICC) range Interobserver (ICC) range Interinstrument (ICC) range Color Kerckhove et al., 2001 Minolta Chromameter CR-300 0.98–0.99 0.92–0.99 0.99–0.999 Uter et al., 2013

Minolta Chromameter CR-300