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Received: 21 February 2019    Revised: 17 March 2019    Accepted: 21 March 2019

DOI: 10.1111/jocd.12964

ORIGINAL CONTRIBUTION

Efficacy and tolerability of using platelet‐rich plasma versus

chemical peeling in periorbital hyperpigmentation

Noura F. Ellabban MSc1 | Moustafa Eyada MD2 | Hesham Nada MD2 |

Noha Kamel MD3

1
Dermatology & Andrology
Department, Ministry of Health, Mansoura,
Egypt
2
Dermatology, Andrology & STDs
Department, Faculty of Medicine, Suez
Canal University, Ismailia, Egypt
3
Clinical Pathology Department, Faculty of
Medicine, Suez Canal University, Ismailia,
Egypt
Correspondence
Noha Kamel, Clinical Pathology Department,
Faculty of Medicine, Suez Canal University,
4.5 K, Ring Road, Ismailia, Egypt.
Email: nkamel30@yahoo.com
Abstract
Background: Various therapeutic modalities for periorbital hyperpigmentation (POH)
have been proposed.
Objective: This study was designed to compare the efficacy and tolerability of au‐
tologous platelet‐rich plasma (PRP) and chemical peeling in POH.
Subjects and methods: Forty‐two patients were enrolled in this study and randomly
subdivided into two groups. Group A patients were assigned to receive four sessions
of chemical peeling using trichloroacetic acid and lactic acid, while group B was as‐
signed to patients who received four sessions of PRP injection with 2 weeks of inter‐
vals. Patients were assessed by digital photographs. The degree of improvement
included four degrees from poor to excellent, and side effects were reported.
Results: Females constituted 38 out of 42 patients (mean age, 28.14 ± 3.47 years).
There was a significant improvement in favor of chemical peeling over PRP. Good
improvement occurred in 47.6% in the group A versus 4.8% in group B (P < 0.001).
None of the PRP group had excellent improvement, while 38% of chemical peeling
group did. Most of group A patients reported very pleased (47.6%) to excellent (38%)
degree, in contrast to group B where 52.5% were just pleased (P < 0.001). Some of
group A patients experienced itching (14.3%) and redness (14.3%), while in group B,
they experienced pain (23.8%) and edema (14.3%) with nonsignificant difference be‐
tween both groups (P = 0.07).
Conclusions: Both PRP and chemical peeling are effective for treatment of POH;
however, chemical peeling is much more effective, tolerable, and satisfying proce‐
dure than PRP.

KEYWORDS
chemical peel, patient satisfaction, periorbital hyperpigmentation, platelet‐rich plasma

1 |  I NTRO D U C TI O N
Periorbital hyperpigmentation (POH) (also known as dark eye cir‐
cles, periorbital melanosis, and infraorbital darkening) implies a com‐
mon cosmetic skin condition with bilateral relative darkness of the
periorbital eyelids. Both sexes are affected, becoming worse with
aging, and it makes people looks older and tired affecting the quality
of life adversely especially in females.1
Many endogenous and exogenous etiologies are implicated
in POH pathogenesis including heredity or genetic, excessive

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2       ELLABBAN et al.
vascularity, facial structure, shadowing due to skin laxity, and tear
trough associated with aging, postinflammatory hyperpigmentation
secondary to atopic and allergic contact dermatitis, smoking, alcohol
consumption, disturbed sleeping, and sun exposure may play a role
in the formation of these dark circles. 2,3
Several treatment modalities have been recommended for POH;
however, there are scarce number of studies on their long‐term ef‐
ficacy and safety. Topical application of depigmenting (bleaching)
agents, chemical peeling, carboxytherapy, laser therapies, injectable
fillers, dermabrasion, and autologous fat transplantation are among
various types of available treatments.4
Platelet‐rich plasma (PRP) is a hemoconcentrate with platelets
concentration above baseline values obtained from centrifugation
of autologous whole blood.5 Platelet‐rich plasma has been proved
to be a highly beneficial bio‐regenerator in various applications in
different fields of medicine, including dermatology.6 It has a high
concentration of many growth factors, chemokines, and cytokines
and has been applied to encourage various healing and regenerative
processes.7 Platelet‐rich plasma application has been found to be
effective for wrinkles, laxity, and secondary POH‐related dark cir‐
cles.8 Furthermore, PRP is utilized in combination with autologous
fat grafts for dark circles. Transforming growth factor‐β1 and epider‐
mal growth factor in PRP are suggested to reduce melanin produc‐
tion through delayed extracellular signal‐regulated kinase activation
and suppression of prostaglandin‐E2 expression/tyrosinase enzyme
9
activity.
Chemical peeling is used to treat a diversity of facial pigmentary
conditions as the peeling agents eliminate melanin from the stratum
corneum and epidermis.10 A previous report has documented signif‐
icant improvement when 10% trichloroacetic acid (TCA) was applied
in patients with dark circles.11
Comparative studies are highly recommended to determine the
efficacy of PRP and chemical peeling in POH. To the best of our
knowledge, this is the first study designed to compare the therapeu‐
tic effectiveness and tolerability of using PRP and chemical peeling
in the treatment of POH.
2 |  S U B J EC T S A N D M E TH O DS
2.1 | Subjects
Forty‐two patients with POH were recruited from the outpatient
clinics of Dermatology and Venereology Department of Suez Canal
University Hospitals from March 2017 to December 2017. After ap‐
proval from the research ethics committee of faculty of Medicine,
Suez Canal University, an informed consent was taken from every
patient after full explanation of the procedure and possible side ef‐
fects of the study.
Newly diagnosed patients who were otherwise clinically free and
not receiving topical treatment for the last 6 months were enrolled
in this study. Exclusion criteria included all patients with history of
keloid scarring, photosensitivity or hypersensitivity to the treat‐
ment components, patients with local inflammatory skin disorders
or active herpes infection at the site of the procedure, corticoste‐
roid injection at treatment site within 6 months, systemic use of
corticosteroids within 2 weeks, recent fever, chronic medical illness,
pregnant females patients with known bleeding tendency, platelet
dysfunction, thrombocytopenia (platelets count <150×109/L), and
patients on regular use of anticoagulant or antiplatelet drugs.
2.2 | Methods
All patients were subjected to detailed history taking, thorough gen‐
eral and dermatological examination. Assessment of the grades of
POH before and after intervention was conducted in comparison
with the surrounding skin as follows:4
Grade 0: Skin color comparable to other facial skin areas.
Grade 1: Faint pigmentation of infraorbital fold (bilateral).
Grade 2: Pigmentation more pronounced.
Grade 3: Deep dark color, all four lids involved.
Grade 4: Grade 3 + pigmentation spreading beyond infraorbital fold.
The patients were randomly divided into two groups; group A and
B, each group consisted of 21 patients. For group A patients, a peeling
agent consisted of combined TCA 3.75% and lactic acid (LA) 15% in a
gel formula to increase the depth of penetration without increasing the
concentration of the used agents was applied to the infraorbital areas
every 2 weeks for four sessions. Group B patients were subjected to
four sessions of autologous PRP injections into the infraorbital areas
with 2 weeks’ interval between the sessions.
2.2.1 | Chemical peeling
Patients were instructed to keep their eyes closed. A soaked wipe
with acidified hydroalcoholic solution and citric acid was used for
cleaning. Four layers of the peel were applied to each infraorbital
area. The first layer was applied starting from the most intense area
of hyperpigmentation. The duration of the first three layers ranged
between 1 and 2 min, and the last layer was about 5 min with a ses‐
sion duration ranged between 8 and 11 min. Then, the patients were
instructed to wash the infraorbital area with pure water and to avoid
rubbing the infraorbital area and direct sunlight, and to use sun‐
screen and wear sunglasses.
2.2.2 | Platelet‐rich plasma
A topical anesthetic cream was applied under an occlusive dressing
for an hour and subsequently washed off to obtain completely dry
skin surface.
Ten milliliter (mL) of whole blood was withdrawn from each pa‐
tient and collected in a sterile tube containing 1 mL anticoagulant
(trisodium citrate). The centrifugation process separates blood com‐
ponents owing to their different specific gravities, that is, RBCs being
the heaviest, followed by WBCs, whereas platelets and plasma are
the lightest. A two‐step centrifugation in a temperature‐controlled
ELLABBAN et al.
TA B L E 1   Demographic characteristics and risk factors for the
studied patients (N = 42)
Variables  
Age, years (mean ± SD) 28.14 ± 3.47
Gender, N (%)
Female 38 (90.5)
Male 4 (9.5)
Risk factors
Cigarette smoking, N (%)
Nonsmoker 35 (83.3)
Smoker 7 (16.7)
Anemia, N (%)
Normal hemoglobin 34 (81)
Low hemoglobin 8 (19)
centrifuge (18°C) was performed, a low spin centrifugation step to
avoid spinning down platelets and to isolate plasma (centrifugation
at 150 g for 5 min). Then, all the supernatant plasma was aspirated
by sterile syringe and collected from the tube in a sterile plain tube.
A second hard spin at 2000 g for 12 min was adopted to obtain two
layers; around two‐thirds of the supernatant platelet‐poor plasma
were discarded and the platelet‐rich pellet is re‐suspended in the
residual amount of plasma.
The platelet count in the obtained PRP was estimated to be 3‐ to
4‐fold concentrated than in the whole blood. The resulting PRP was
aspirated, and 0.1 mL of calcium chloride was added for each 0.9 mL
of PRP for platelets activation and then injected into the selected
area using insulin syringe needle for superficial microinjection.
Disinfection and cleaning of the skin were done before and after
injection using alcohol 70%. Topical antibiotics and a moisturizing
cream were prescribed following each session, and the patients were
informed to apply a sunscreen all along the treatment course.
2.2.3 | Therapeutic outcomes
Therapeutic outcomes were scored using the following four‐
point scale: 0%‐25% (poor), 26%‐50% (fair), 51%‐75% (good), and
76%‐100% (excellent).
The patients were requested to rate their individual level of sat‐
isfaction by giving themselves a score on a scale from 0 to 4: 0 = no
change, 1 = satisfied, 2 = pleased, 3 = very pleased, and 4 = excel‐
lent.5 Tolerability was evaluated by asking the patient about the
presence of adverse effects: burning, edema, itching, pain, redness,
ecchymosis, or none.
Two dermatologists took photographs using digital camera (Sony
megapixels, Tokyo, Japan), three photographs were taken prior to
treatment for both sides and the front of the face, and then another
group of photographs were taken in each visit following treatment
using identical camera settings, lighting, and patient positioning. All
patients were followed up for 2 months to evaluate the level of im‐
provement or recurrence of the infraorbital hyperpigmentation.
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2.3 | Statistical analysis
The Statistical Package for Social Science (SPSS, version 20.0)
software was utilized for data statistical analysis. Quantitative
data were expressed as means ± SD and ranges, while qualitative
data were expressed as numbers and percentages at 95% confi‐
dence interval (CI). For comparing the two groups, t test and Mann‐
Whitney U test were used to test a significance of difference for
quantitative variables and paired t test was used to compare the
same group before and after intervention. Correlation between
variables was evaluated using Pearson's correlation coefficient.
A probability value of P value < 0.05 was considered statistically
significant.
3 | R E S U LT S
The demographic criteria and risk factors of the 42 patients are
shown in Table 1. The initial assessment of POH grades revealed
that 23 patients (54.8%) had Grade 3 (deep dark circles), 14 pa‐
tients (33.3%) had Grade 2 (pigmentation more pronounced), while
only three patients (7.1%) were Grade 4 (Grade 3 plus pigmenta‐
tion spreading beyond) and two patients (4.8%) were Grade 1 (faint
pigmentation).
There were statistically nonsignificant relations between grades
of dark circles and gender, age, cigarette smoking or presence of
anemia (P values were 0.81, 0.64, 0.32, and 0.26 respectively).
There was nonsignificant difference between both groups be‐
fore starting therapy. On comparing the grades of POH before and
after completing treatment, in both groups, there was statistically
significant improvement. Furthermore, when evaluating grades of
POH in both groups after intervention, a high statistically significant
difference in favor of the group treated with chemical peeling was
found (P < 0.001) (Table 2).
When the degree of improvement of periocular dark circles was
compared between chemical peeling and PRP effects, there was a
high statistically significant difference in favor of chemical peeling (P
value < 0.001) (Table 3) (Figure 1A,B).
There was a high statistically significant difference between
both groups regarding degree of patient satisfaction in favor of
chemical peeling where 10 patients (47.6%) were very pleased and
eight patients (38%) had excellent satisfaction while only two (9.5%)
and one (4.8%) were pleased and satisfied, respectively. In contrast
to the group treated with PRP, where none showed excellent satis‐
faction, four patients (19%) were very pleased, 11 patients (52.5%)
were pleased, four patients (19%) were satisfied, and two patients
(9.5%) had no change.
There have been some adverse effects with nonsignificant differ‐
ence between both groups. The most common adverse effects with
chemical peeling were redness and itching occurred in three patients
(14.3%), while only one patient experienced burning, edema, or pain.
In group B, five patients (23.8%) experienced pain, three patients
(14.3%) had edema, and only one patient (4.8%) had ecchymosis.
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4       ELLABBAN et al.

TA B L E 2   Comparison between both groups and grades of 4 | D I S CU S S I O N

periocular dark circles before and after intervention

Number (%) Periorbital hyperpigmentation is a relatively common problem

Grades of infraorbi‐ caused by various etiologies with no treatment of choice. With
tal dark circles Chemical peeling PRP P value
many aesthetic modalities evolving, the best treatment would rotate
Before intervention around identification of the etiology and eliminating the risk factors
Grade 0 0 (0) 0 (0) 0.318 in individual basis. The pervasive use of autologous PRP in many
Grade 1 2 (9.5) 0 (0) medical conditions especially in dermatology leads us to design the
Grade 2 5 (23.8) 9 (42.9) current study to compare the tolerability and efficacy of PRP and

Grade 3 12 (57.2) 11 (52.3) chemical peeling in POH patients.

Platelet‐rich plasma is known to enhance dermal elasticity as it
Grade 4 2 (9.5) 1 (4.8)
stimulates the elimination of damaged extracellular matrix and in‐
After intervention
duces synthesis of new collagen.12
Grade 0 8 (38) 2 (9.5) <0.001** 
Platelet α‐granules secrete many growth factors which are in‐
Grade 1 12 (57.2) 5 (23.8)
volved in various treatment targets.13 Transforming growth fac‐
Grade 2 1 (4.8) 9 (42.9)
tor β1 (TGF‐β1) was found to inhibit melanin synthesis and reduce
Grade 3 0 (0) 5 (23.8) the activity of tyrosinase, the rate‐limiting melanogenic enzyme.14
Grade 4 0 (0) 0 (0) Epidermal growth factor (EGF) was reported as a candidate target
P value <0.001**  for development of anti‐melanogenic agents in postinflammatory
**High statistically significant P value. hyperpigmentation.15 To our knowledge, there are limited studies
comparing the effects of PRP versus other treatment modalities in
POH.3,5,13
A previous study which was conducted on fifty Jordanian pa‐
TA B L E 3   Comparison between both groups according to the tients to evaluate the effectiveness of PRP on POH, the author
degree of improvement found that (4%) of the patients reported excellent improvement,
(12%) reported significant improvement, (46%) moderate improve‐
Number (%)
Degree of ment, and (38%) mild improvement in the appearance of POH.5
improvement Chemical peeling PRP P value In another study from Iran, Mehryan and colleagues studied the
Poor 1 (4.8) 12 (57.2) <0.001**  effect of single session of intradermal injections of 1.5 mL of PRP
Fair 2 (9.6) 8 (38) given into the tear trough area in ten patients. The effect was com‐
Good 10 (47.6) 1 (4.8) pared to the baseline 3 months later. They observed no significant
changes in melanin content, whereas they stated that PRP may have
Excellent 8 (38) 0 (0)
the potential to improve POH in terms of color homogeneity of the
**High statistically significant P value.
region.13

F I G U R E 1   A, Patient with POH (before

and after) treated with PRP with good
improvement. B, Patient with POH (before
and after) treated with chemical peeling
with excellent improvement

(A) (B)
ELLABBAN et al.
Efficacy of PRP in the rejuvenation of lower eyelid skin was
tested by Kang and his colleagues in twenty Asian patients. They
asserted that PRP injections given monthly for 3 months have shown
very good results for infraorbital rejuvenation.8 In a Korean study by
Shin and coauthors, they tested a combination of fractional nonab‐
lative laser therapy with topical application of PRP for skin rejuve‐
nation, they declared a significant increase in subjective satisfaction,
skin elasticity, and erythema index; however, objective clinical as‐
sessment showed mild nonsignificant improvement.16
In a Turkish study, melasma was effectively treated after three
sessions of PRP.17 The result was better than those of the current
study since POH etiology is multifactorial than melasma. Although
there is a discrepancy in results, both studies demonstrate that PRP
is a good treatment option for facial hyperpigmentation.
In the current work, the correlation between some variables
and the degree of POH was studied, and there were nonsignificant
correlations between the degree of halos’ color and gender, age,
cigarette smoking or presence of anemia. In contrast, Ranu and his
colleagues found that smoking is one of the environmental causes
of POH.18 Another study stated that POH was most prevalent in
16‐25 years’ age‐group and half of their studied population had
19
anemia.
The current study results showed that about half of the patients
treated with chemical peeling showed good improvement in contrast
to those treated with PRP where 57.2% reported poor improvement
and none showed excellent response. Previous studies have shown
good results when using chemical peelings (15% LA in association
with 3.75% TCA) with brightening and improvement of the dark
circles.4,20
Another study compared the effect of topical bleaching agent
(4% hydroquinone) and 30% salicylic acid peel for 12 weeks, and
studied the effect on the quality of life in POH patients in both
groups. The authors found that both modalities significantly im‐
proved the dermatological life quality index of the patients with no
significant difference found between them. 21
Because of its autologous nature, PRP is applied without any seri‐
ous adverse effects, aside from local injection site reactions like pain or
secondary infection, which can be precluded with proper precautions.
Nevertheless, about one‐third of them complained from recurrent
blood withdrawal for PRP preparation. Unlike PRP, most common side
effects from chemical peeling were redness and itching which are re‐
ported by previous studies as a result of contact dermatitis.4,20
As the aim of POH treatment is aesthetic improvement, patient
perception of the treatment outcome appears to be the foremost
goal. In this study, about 86% of patients treated with chemical
peeling reported being very pleased and excellent with treatment in
contrast to only 19% of patients treated with PRP with highly signif‐
icant difference between both groups. These results disagreed with
another study in which about 66% of patients were pleased or very
pleased with end results using PRP.5
This study has certain strength point as to the best of our knowl‐
edge it is the first comparative study to evaluate the tolerability and
effectiveness of PRP versus chemical peeling in POH. The patient
|
      5
satisfaction was taken into consideration as it is an important sub‐
jective scale.
The study has some weakness points including relatively small
sample size. More randomized trials on larger sample size are
needed to validate using PRP solely or in combination therapy with
other treatment options. Extending the follow‐up to 6 months after
treatment to assess the recurrence is recommended.
5 | CO N C LU S I O N S
We can conclude that using intradermal injection of PRP for the
treatment of POH has slightly improved the clinical outcome but on
comparing its effect with chemical peeling using TCA 3.75% com‐
bined with LA 15%, the improvement was much higher with the
latter and minimal tolerated side effects. It is a cheap and simple
in‐office procedure.
C O N FL I C T O F I N T E R E S T
The authors declare that they have no financial or nonfinancial con‐
flicts of interest related to the subject matter or materials discussed
in this manuscript.
E T H I C A L A P P R OVA L
All authors hereby declare that all procedures have been examined
and approved by the ethics committee of Faculty of Medicine, Suez
Canal University, Ismailia, Egypt.
ORCID
Noha Kamel  https://orcid.org/0000-0002-8990-2312
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How to cite this article: Ellabban NF, Eyada M, Nada H,
Kamel N. Efficacy and tolerability of using platelet‐rich
plasma versus chemical peeling in periorbital
hyperpigmentation. J Cosmet Dermatol. 2019;00:1–6. https://
doi.org/10.1111/jocd.12964