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Printed in Singapore All rights reserved Published by John Wiley & Sons Ltd
doi: 10.1111/srt.12258 Skin Research and Technology
Background: Dark circles refer to a symptom that present for 8 weeks. The effective parameters (L*, a, M.I., E.I., quasi
darkness under the eyes. Because of improvement in the qual- L*, quasi a* and dermal thickness) were measured during the
ity of life, the dark circles have been recognized as one of study period. Result showed that the L* value of Chromame-
major cosmetic concerns. However, it is not easy to classify terâ, Melanin index (M.I.) of Mexameterâ and quasi L* value
the dark circles because they have various causes. obtained by image analysis improved with statistical signifi-
Methods: To select suitable instruments and detailed evalua- cance after applying the test product compared with the pla-
tion items, the dark circles were classified according to the cebo product.
causes through visual assessment, Wood’s lamp test, and Conclusion: We classified the dark circles according to the
medical history survey for 100 subjects with dark circles. After causes of the dark circles and verified the reliability of the
the classification, were newly recruited for instrument confor- parameter obtained by the instrument conformity assessment
mity assessment. Through this, suitable instruments for dark used in this study through the efficacy evaluation. Also based
circle evaluation were selected. We performed a randomized on this study, we were to suggest newly established methods
clinical trial for dark circles, a placebo-controlled double-blind which can be applied to the evaluation of efficacy of functional
study, using effective parameters of the instruments selected cosmetics for dark circles.
from the preliminary test.
Results: Dark circles of vascular type (35%) and mixed type Key words: dark circles – causes – classification – evaluation
(54%), a combination of pigmented and vascular types, were
the most common. Twenty four subjects with the mixed type Ó 2015 John Wiley & Sons A/S. Published by John
dark circles applied the test product (Vitamin C 3%, Vitamin A Wiley & Sons Ltd
0.1%, Vitamin E 0.5%) and placebo on randomized split-face Accepted for publication 29 July 2015
“dark circles” is not a medical term et al. studied periorbital biopsies of 12 Japanese
T HE TERM
but is being used by many people in gen-
eral to indicate pigment muscle under the eyes
patients with dark circles, showing that all of
them had dermal melanosis via histology (1).
(1). Dark circles can be caused by a variety of This is a common symptom frequently
conditions such as infection, inflammation, described as tired eyes. Although dark circles
allergies, and lifestyle factors. Possible causative may be the result of facial aging, they can affect
factors of the dark circles include excessive pig- both men and women of all ages and have a
mentation; thin and translucent lower eye-lid variety of causes. They can be a significant cos-
skin overlying the orbicularis oculi muscle; and metic concern, and many individuals seek treat-
shadowing due to skin laxity and tear trough ment for this common condition. There are
(2). various cosmetic products and dermatological
The reason why the skin around the eye treatments for those who are concerned about
appears dark is because the skin tissues around the dark circles. Despite its prevalence, there
the eyes are very thin. As the skin ages, the are few published studies about dark circles
lipid layer under the eyes sags and bulges out and its pathogenesis (4). As the individual
to create shadows and make the area darker. anatomical basis for dark circles is not clearly
Excessive pigmentation under the eyes can be a defined and it is not easy to classify the dark
frequent cause of dark circles (3). Watanabe circles because they have various causes.
276
Evaluation method of dark circles
The purpose of this study is to classify the were evaluated by the image analysis program
dark circles according to the causes and then (Image-Pro Plus, Rockville, MD, USA). The quasi
set up the objective methods for optimized eval- L*, and quasi a* values were derived from the
uation of the dark circles. To select suitable Red, Green, and Blue values. The L* and a*
instruments and detailed evaluation items, the parameters were obtained from under the eyes
dark circles were classified according to the using Chromameter CR-400 (Minolta, Tokyo,
cause through visual assessment, Wood’s lamp Japan). Mexameter MX18 (Courage and Khaz-
test and medical history survey for 100 subjects aka, Electronic GmbH, Cologne, Germany) was
with dark circles. We performed efficacy evalu- used to measure the melanin index (M.I.) and
ation of the dark circles after the pre-test for erythema index (E.I.) under the eyes. The dermal
classification by causes of dark circles. The flow density and skin thickness were analyzed using
chart of the study design is shown in Fig. 1. Dermascan-C (Cortex Technology, Hadsund,
Denmark), a high resolution imaging machine
using 20 MHz supersonic waves which is very
Materials and Methods useful in non-invasively observing changes to
Conformity assessment through pre-test the inner layers of the skin. The cutaneous blood
The subjects were consisted of 100 healthy flow under the eyes was measured using Laser
Korean females (mean age, 41.3 years). The Doppler Perfusion Imager (LDPI, PeriScan PIM
study was conducted after obtaining Indepen- II; Perimed AB, J€arf€alla-Stockholm, Sweden) with
dent Ethics Committee’s approval. Volunteers fixed conditions; blocking off all the lights and
aged between 19 and 56 years of age, with dark analyzing by image analysis software (LDPIwin
circles and those who gave written informed con- version 2.6, Perimed AB).
sent were enrolled in the study. To select the suit-
able instruments and detailed evaluation items,
the dark circles were classified according to the Efficacy evaluation
cause through visual assessment, Wood’s lamp This step was to confirm the appropriate evalu-
test, and medical history survey. After the classi- ation method of dark circles using the effica-
fication of dark circles by causes, we measured cious material. Based on the conformity test, we
the dark circle sites to identify any differences performed efficacy evaluation on largest group,
between the dark circle and normal groups. dark circles of mixed type having both the vas-
cular and pigment components with the mix-
ture of retinol, vitamin C, and E. Twenty-four
Measurement and instruments healthy female patients between 20 and
Prior to the study, the subjects stood by at least 59 years of age and clinically diagnosed with
for 30 min in a controlled room at constant tem- dark circles of mixed type by dermatologist,
perature and humidity (20–24°C, 40–60% RH). participated voluntarily in the clinical study.
The subject’s frontal face was photographed We use the selected parameters from the pre-
by Visia-CR (Canfield, Fairfield, NJ, USA) which liminary test for efficacy evaluation. The volun-
is equipped with chin supports and forehead teers with dark circles applied the test product
clamps that fix the face during the photograph- (Vitamin C 3%, Vitamin A 0.1%, Vitamin E
ing process and maintain a fixed distance 0.5%) and placebo on randomized split-face
between the subjects and the camera at all times. with double blind for 8 weeks. During the test-
Using the images from Visia-CR, the dark circles ing period, the subjects visited the laboratory
three times (baseline, 4 weeks, and 8 weeks).
9DVFXODUW\SH
The subjects used the test products and placebo
every morning and night on under-eye area.
3LJPHQWHGW\SH The test product was randomly applied on the
either of the half face (left or right) for each
0L[HGW\SH
subject. They were also instructed to avoid
9DVFXODU3LJPHQWHG
exposure to the sun, excessive exercise, and
(WF(\HEDJ
drinking alcohol prior to each visit. Visual
assessment was performed using our dark
Fig. 1. Classification of subjects according to causes of dark circles. circles grading scale from 0 to 5 (Fig. 2). To ver-
277
Park et al.
ify the reliability of the evaluation methods of q was used to correlate each parameter. Signifi-
dark circles, the validation of the identically cance was measured at P < 0.05.
designed trial was conducted at dermatology of
Inha University hospital.
Result
Conformity assessment
Statistical analysis Classification of dark circles by causes
The differences among three groups by cause of As a result of the classification of dark circles
dark circles (vascular type, mixed type, and among 100 females, the vascular type (35%) and
normal) were analysed using one-way ANOVA, the mixed type (54%), a combination of pig-
Welch test and Kruscal–Wallis test, with post- mented and vascular dark circles, were most
hoc analysis based on Scheffe, Games-Howell, common. The pigmented type, without vascular
and Mann–Whitney (Bonferrony correction) component and structural type such as eye bags
post-hoc comparisons. Contrast test was per- accounted for 5% and 6% respectively (Fig. 1).
formed by repeated measures ANOVA (RM-ANOVA) Therefore, to examine which equipment is
to compare the changes between the product appropriate for efficacy evaluation of dark cir-
application side and the placebo application cles, we conducted preliminary test on the sub-
side at different time points. RM-ANOVA was also jects with the mixed type, vascular type, and
used to compare the changes of each site those without dark circles. Subjects classified as
between every time point. The inter-class corre- having vascular type had dark circles below the
lation coefficients were then calculated from the eyes that appeared red/purple. The tone was
between-reader error variance and the total darker inside than outside. When the skin was
variance at visual assessment. Also, Spearman’s pulled, the purplish tone tended to become dar-
278
Evaluation method of dark circles
ker, but did not become any more obvious the vascular type and that of the normal group
under Wood’s lamp. Dark circles which with statistical significance (P < 0.05); however,
appeared brown/gray were observed from the there was no significant difference in the values
subjects classified as having pigmented dark between the vascular type and the normal
circles. Dark circles became more distinguish- group. For E.I. value, the value of the mixed
able under Wood’s lamp. Subjects with the type was higher than that of the normal group
mixed type showed the tone of dark circles sim- with statistical significance (P < 0.05), but there
ilar to the vascular dark circles, which appeared was no significant difference in the values
red/purple. Solar lentigo and non specific pig- between the vascular type and the normal
mentation were also observable on dark circle group. L* value of the mixed type was lower
area. Under Wood’s lamp, pigmentation and than that of the vascular type and that of the
blemish around the dark circles became more normal group with statistical significance
obvious (Fig. 3). (P < 0.05) and the value of the vascular type
was lower than that of the normal group with
Evaluation of instrument suitability statistical significance (P < 0.05). For a* value,
Conformity assessment was performed on the the value of the mixed type was higher than
subjects with the most frequent patterns, the the normal group with statistical significance
vascular type (22 females; mean age, (P < 0.05) however, there was no significant dif-
41.8 years), the mixed type (24 females; mean ference in the values between the vascular type
age, 43.0 years), and those without dark circles and that of the normal group (Table 2). The
(21 females; mean age, 38.4 years), to select quasi L* value of the mixed type was the
appropriate index of the dark circle evaluation. lowest in 3 groups and the quasi L* value of
The homogeneity between each group was the vascular type was lower than the normal
established by checking the M.I. and E.I. of the group with statistical significance (P < 0.05).
cheek area before actual test. There were no sig- Quasi a* values showed the contrast tendency
nificant differences in M.I. and E.I. between against quasi L* value with statistical signifi-
each group. As indicated in Tables 1 and 2, M.I. cance (P < 0.05). The dermal thickness of the
value of the mixed type was higher than that of normal group was significantly higher than that
Fig. 3. Characteristics of subjects based on dark circles causes. Photographs obtained with Visia-CR.
279
Park et al.
TABLE 1. Mean values SD of each parameter on dark circles area TABLE 3. Mean values and SD measured on dark circles during
among the groups treatment with the test product and placebo in split-face randomly for
8 weeks
Without dark
circles Mixed type Vascular type Test material Placebo
280
Evaluation method of dark circles
281
Park et al.
(a) (b)
(c) (d)
Fig. 4. Changes in mean values ± SD measured at dark circles during the treatment with the test product (Vitamin C 3%, Vitamin A 0.1%, Vita-
min E 0.5%) and the placebo in split-face randomly for 8 weeks. (a) M.I. value measured by Mexameter (b) L* value measured by Chromameter
(c) Quasi L* value measured by image analysis obtained with Visia-CR (d) Dermal thickness measured by Dermascan-C. **One way ANOVA post-
hoc Scheffe, P < 0.05; ***One way ANOVA post-hoc Scheffe, P < 0.001.
parameters. Therefore, the dermal thickness through the efficacy evaluation. Also, based on
alone may not be enough to be used as the this study, we have suggested new methods
major parameter for efficacy evaluation but only and scoring grade which can be applied to the
as a reference indicator. In this study significant evaluation of efficacy of for dark circles. It is
improvement in parameters for dark circles was important in the development of cosmetics and
observed in 8 weeks. Furthermore, we con- dermatological treatment methods in differenti-
firmed that the results of dermatology by Inha ating the main cause of the dark circles before
University hospital, the validation institution treatment and select appropriate methods
showed a similar tendency. Therefore, this corresponding to the cause.
evaluation method is considered to be reliable
for dark circle evaluation. Acknowledgments
In conclusion, we classified the dark circles
according to the causes and verified the reliabil- This research was supported by a grant
ity of the parameters obtained by instrument (13172KFDA460) from Korea Food and Drug
conformity assessment used in this study Administration in 2013.
References ruby laser. Dermatology Surg 2006; 3. Roh MR, Chung KY. Infraorbital
32: 785–789. dark circles: definition, causes, and
1. Watanabe S, Nakai K, Oshushi T. 2. Lowe NJ, Wieder JM, Shorr N, treatment options. Dermatol Surg
Condition known as “dark rings Boxrud C, Saucer D, Chalet M. 2009; 35: 1163–1171.
under the eyes” in the Japanese Infraorbital pigmented skin. Pre- 4. Freitag FM, Cestari TF. What
population is a kind of dermal liminary observations of laser causes dark circles under the eyes.
melanocytosis which can be suc- therapy. Dermatol Surg 1995; 21: J Cosmet Dermatol 2007; 6: 211–
cessfully treated by Q-switched 767–770. 215.
282
Evaluation method of dark circles
5. Oresajo C, Dickens M, Znaiden A. 9. Chung JH, Youn SH, Kwon OS, 12. Lou WW, Quintana AT, Gerone-
Eye area problems puffiness, bags, Cho KH, Youn JL, Eun HC. Regu- mus RG, Grossman MC. Effects of
dark circles and crowsfeet. Cosmet lations of collagen synthesis by topical vitamin K and retinol on
Toiletries 1987; 102: 29–34. ascorbic acid, transforming growth laser-induced purpura on nonle-
6. Matsumoto M, Kobayashi N, factor-beta and interferon-gamma sional skin. Dermatol Surg 1999;
Osamu H, Arai S. Study on the in human dermal fibroblasts cul- 25: 942–944.
mechanisms associated with dark tured in three-dimensional collagen 13. Lupo MP. Antioxidants and vita-
circles. J Soc Cosmet Chem 2000; gel are photoaging-and aging-inde- mins in cosmetics. Clin Dermatol
34: 152–159. pendent. J Dermatol Sci 1997; 15: 2001; 19: 467–473.
7. Ohshima H, Takiwaki H. Evalua- 188–200.
tion of dark circles of the lower 10. Mitsuishi T, Shimoda Y, Mitsui Y,
eyelid: comparison between reflec- Kuriyama Y, Kawana S. The Address:
tance meters and image processing effects of topical application of S. R. Park
and involvement of dermal thick- phytonadione, retinol and vitamins Ellead Skin and Bio Research
ness in appearance. Skin Res C and E on infraorbital dark cir- 325, Hwangsaeul-ro, Bundang-gu
Technol 2008; 14: 135–141. cles and wrinkles of the lower eye- Seongnam-si
8. Hakozaki T, Takiwaki H, Miya- lids. J Cosmet Dermatol 2004; 3: Gyeonggi-do 463-824
moto K, Sato Y, Arase S. Ultra- 73–75. Korea
sound enhanced skin-lightening 11. Elson ML. Topical phytonadione Tel: +82 31 709 9070
effect of vitamin C and niaci- (vitamin K1) in the treatment of Fax: +82 31 703 9071
namide. Skin Res Technol 2006; 12: actinic and traumatic purpura. e-mail: srom.pak@gmail.com
105–113. Cosmet Dermatol 1995; 8: 25–27.
283