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Adjunctive Skin Care of the
Brow and Periorbital Region
Vivian W. Bucay, MD
a,b,
*, Doris Day, MD, MA
c,d
INTRODUCTION
The periorbital region is often one of the first areas
to show signs of aging and patients seek a derma-
tologist’s advice regarding care of the eyelid skin,
often starting in their early 20s, well before seeking
other antiaging treatments. In the context of
a multidisciplinary approach to brow and eyelid
rejuvenation, it is the dermatologist’s responsibility
to be familiar with the many skin care options avail-
able for common concerns, including fine lines and
wrinkles, infraorbital dark circles, and under-eye
puffiness. Eyelid anatomy and aging are ad-
dressed in elsewhere in this issue by Lam and
colleagues, Fitzgerald, Pepper and Moyer, Lee
and Baker, Quatela and Lieberman, Day and
Bucay, and Sundaram. They are also discussed
in this article as they concern some key concepts
relevant to understanding the aforementioned
common complaints.
FINE LINES AND WRINKLES
Eyelid skin is the thinnest in the body, at times only
0.2 mm thick, contributing to its susceptibility to
actinic and other damage. UV radiation is the
primary cause of photodamage resulting in fine
lines, mottled pigmentation, and textural changes.
Other factors that lead to skin changes include
genetic predisposition, smoking, and chronic
rubbing due to seasonal allergies, irritants, or
contact dermatitis. Components of adjunctive
skin care to treat the signs of photodamage may
include sunscreen, topical antioxidants, retinoids,
collagen boosters, and DNA repair.
Sunscreens
Sunscreens are an indispensable element of
adjunctive skin care of the eyelids and periorbital
region. Classified as over-the-counter drugs,
a
Private Practice, University of Texas Health Science Center, 326 W. Craig PL, San Antonio, TX 78212, USA;
b
Department of Physician Assistant Studies, University of Texas Health Science Center, 7703 Floyd Curl
Drive, San Antonio, TX 78229, USA;
c
Day Dermatology and Aesthetics, 10 East 70th Street, 1C, New York,
NY 10021, USA;
d
The Ronald O. Perelman Department of Dermatology, New York University Langone Medical
Center, 550 1st Avenue, New York, NY 10016, USA
* Corresponding author. 326 West Craig Place, San Antonio, TX 78212, USA.
E-mail address: vbucay@aol.com
KEYWORDS
Skin care Periorbital Brow Anti-aging cosmeceuticals Antioxidants Retinoids
Growth factors Peptides
KEY POINTS
The unique anatomic characteristics of eyelid skin influence the types of skin care products suited
to this area.
Common concerns, including fine lines and wrinkles, infraorbital dark circles, under-eye puffiness,
and thinning lashes and brows, can be treated by specific ingredients.
Adjunctive skin care to treat the signs of photodamage may include sunscreen, topical antioxi-
dants, retinoids, collagen boosters, and DNA repair enzymes.
Knowledge of the contributing factors in the development of photodamage, dark circles and under-
eye puffiness is needed to make skin care recommendations for these problems.
It is important to set realistic patient expectations regarding the results of adjunctive skin care
therapy.
Clin Plastic Surg 40 (2013) 225–236
http://dx.doi.org/10.1016/j.cps.2012.09.003
0094-1298/13/$ – see front matter Ó2013 Elsevier Inc. All rights reserved.
plasticsurgery.theclinics.com
sunscreens should offer broad UV protection to
include UVA (320–400 nm) and UVB (290–320 nm)
and are integral in preventing UV immunosuppres-
sion.
1
They should contain only ingredients that
have been approved by the US Food and Drug
Administration (FDA) as listed in the FDA’s
Sunscreen Monograph Final Rule.
2
Sunscreens
are generally divided into two classes:
1. Chemical—organic
2. Physical—inorganic.
Chemical sunscreens (eg, benzophenone, ho-
mosalate, methyl anthranilate, octyl methoxycin-
namate, oxybenzone, avobenzone) work by
converting UVB radiation into heat, whereas phys-
ical sunscreens (eg, zinc oxide, titanium dioxide,
kaolin, ichthammol, iron oxide) scatter, reflect
and absorb solar radiation across a broad spec-
trum in the UV and visible ranges. In addition to
their greater chemical stability, physical sun-
screens have the added benefit of a minimal risk
of contact sensitivity, an important consideration
for delicate eyelid skin.
Topical Antioxidants
Topical antioxidants scavenge free radicals, which
are highly unstable and reactive molecules. Free
radicals that are generated from oxygen are known
as reactive oxygen species. Capable of damaging
cellular membranes, DNA, and cellular proteins,
free radicals can be produced by normal cellular
metabolism or can be triggered by external factors,
including UV radiation and cigarette smoking. Skin
aging is generally attributed to a combination of
intrinsic and/or chronologic aging and extrinsic
and/or environmental aging, and reactive oxygen
species play a key role in both types of aging,
a concept first published by Harman
3
in 1956.
Free radicals can also lead to inflammation,
another factor that has been implicated in the aging
process.
4
Vitamin C
Topical vitamin C (ascorbic acid) has been shown
to reduce UV-induced erythema, sunburn cell
formation,
5,6
and the appearance of wrinkles.
7,8
A combination of topically applied water soluble
vitamin C (ascorbic acid), and a lipid soluble
form, tetrahexyldecyl ascorbate (THD), has also
been shown to reduce wrinkling due to photodam-
age.
9
Studies have shown that, at the same
concentration, THD surpasses the depth of pene-
tration of ascorbic acid by threefold and that its
rate of penetration is greater, even when the
concentration of ascorbic acid is 25 times that of
THD.
10
Vitamin C plays an important role in
collagen production and has been shown to stim-
ulate collagen production when added to cultures
of human skin fibroblasts.
11
Vitamin C also
restores the antioxidant capacity of vitamin
E,
12,13
a much more potent inhibitor of lipid
peroxidation.
Vitamin E
Vitamin E is lipid soluble and consists of eight
active isomers (tocopherols and tocotrienols),
with alpha-tocopherol showing the most biologic
activity. Vitamin E reduces the number of sunburn
cells, decreases UVB-induced photodamage,
14
and can inhibit UV-induced tumor formation.
15
Alpha-tocopherol, a membrane-bound antioxi-
dant, protects cell membranes from damage
caused by phospholipase A, lysophospholipids,
and free fatty acids.
14
Vitamin E has been shown
to inhibit human macrophage metalloelastase,
a matrix metalloproteinase (MMP) that degrades
elastin.
15
Furthermore, signs of photoaging were
shown to improve in a study comparing the use
of a vitamin E cream versus placebo.
16
Combined vitamins C and E
The combined application of Vitamins E and C that
is commercially available in several product lines
has been shown to provide more potent photopro-
tection compared with either agent alone.
6
A limi-
tation to topically applied vitamin E is the potential
for contact dermatitis.
17,18
Green tea
Green tea antioxidants extracted from the leaves
and buds of the plant Camellia sinensis include epi-
catechin, epicatechin-3-gallate, epigallocatechin,
and epigallocatechin-3-gallate (EGCG), the latter
being the most abundant and potent.
19
Animal
studies have shown that topically applied green tea
polyphenols can inhibit photocarcinogenesis
20
as
well as prevent UV-induced oxidative damage and
induction of MMPs.
21
In vivo application of green
tea polyphenols to human backs 30 minutes before
UV irradiation was shown to reduce erythema, the
number of sunburn cells, immunosuppression,
22
and DNA damage.
23
Another study demonstrated
the efficacy of topically applied EGCG in reducing
UVB-induced inflammation.
24
Although controlled
clinical trials are lacking, green tea polyphenols are
popular in cosmeceuticals given their ability to multi-
task. Vivian W. Bucay find them very helpful in miti-
gating the retinoid-induced irritation.
Vitamin B3
Topically applied niacinamide, the biologically
active form of vitamin B3, not only exhibits antiox-
idant and antiinflammatory properties
25
but also
can improve hyperpigmentation by decreasing
Bucay & Day
226
transfer of melanosomes to keratinocytes. The
effects of topically applied niacinamide include
improved skin texture and tone along with a reduc-
tion in fine lines and hyperpigmentation.
26
Side Effects of Topical Antioxidants
Side effects associated with topical antioxidants
may include allergic contact dermatitis or irritant
dermatitis. Topical vitamin E and niacinamide
may induce allergic contact dermatitis, whereas
irritant dermatitis may occur with some forms of
topical vitamin C, such as the water-soluble forms,
because higher concentrations are required for
efficacy.
Retinoids
Retinoids are a classification of naturally occurring
and synthetic compounds that exhibit the biologic
actions of vitamin A. Their inclusion in countless
antiaging products was triggered by Kligman and
colleagues’
27
groundbreaking research on the
effects of tretinoin on photodamaged skin in 1986.
Prescription retinoids
Of the prescription retinoids, only tretinoin and ta-
zarotene have FDA approval for the treatment of
photodamage, although nonprescription retinol
and retinaldehyde are commonly used for this indi-
cation. Wrinkle improvement is the result of
retinoid-mediated effects that produce an increase
in dermal collagen synthesis by increasing type I
procollagen expression
28
mediated by the inhibi-
tion of the UV-induction of c-Jun
29
and an alteration
of transforming growth factor (TGF)-bexpression.
30
Inhibition of dermal collagen degradation is
accomplished by inhibition of transcriptional factor
activator protein-1 activation of MMP-like
collagenase.
31,32
Retinoids also improve dyschromia by inhibiting
tyrosinase activity. This leads to a reduction of
melanin synthesis, decrease in melanosome trans-
fer, and increase in shedding of keratinocytes.
33,34
Additionally, retinoids contribute to smoother skin
and a reduction in tactile roughness by increasing
epidermal proliferation and differentiation, com-
pacting the stratum corneum, and increasing
epidermal and dermal intercellular mucin
deposition.
35,36
Over-the-counter retinoids
Over-the-counter alternatives include retinol that,
although potentially less irritating than its metabo-
lite retinoic acid (tretinoin), is also 20-fold less
potent.
36
Retinaldehyde, a naturally occurring
metabolite of retinol and the precursor of retinoic
acid, has demonstrated efficacy in treating photo-
damage
37
but with less irritation than retinoic
acid.
38
Eye skin care products containing hyalur-
onic acid, ceramides, cholesterol, and dimethyla-
minoethanol (DMAE) lactate are useful in
mitigating dryness and skin irritation, and main-
taining an adequate skin barrier.
Side Effects of with Retinoids
The most common side effect associated with reti-
noid use is an irritant dermatitis, characterized by
excessive redness, dryness and flaking. This can
be minimized by selecting the appropriate type
of retinoid for the patient’s skin type, for example,
retinoic acid or retinol for someone with thicker,
oilier skin and retinaldehyde for those with thinner,
drier skin. Additional strategies for mitigating skin
irritation include decreasing the amount of product
applied and/or the frequency of application. Layer-
ing the retinoid over a product containing antiin-
flammatory ingredients such as green tea
polyphenols or coffeeberry also reduces skin irrita-
tion. Protective measures regarding sun exposure
are strongly recommended and include
sunscreen, sunglasses, and hats.
Patients should be counseled against using
prescription retinoids during pregnancy and lacta-
tion. The authors recommend that each patient
consult her obstetrician regarding the use of
nonprescription retinoids during pregnancy and
lactation.
Collagen Boosters: Peptides and Growth
Factors
Peptides
Collagen boosters typically include compounds
such as peptides and growth factors. A brief
review of the pathogenesis of aging skin will aid
in understanding the rationale for the use of these
compounds in antiaging products:
Lines and wrinkles occur both in photoaged
and chronologically aged skin
Coarser lines and wrinkles are character-
istic of photoaging, whereas finer lines are
more typical of chronologic aging
The pathogenesis of skin aging is charac-
terized by a decrease in collagen synthesis
coupled with an increase in collagen
breakdown
39
A decrease in procollagen type I mRNA is
seen in aging skin,
40
with a greater reduc-
tion seen in photodamaged skin compared
with nonexposed skin
41
UV radiation–induced upregulation of colla-
genase (MMP-1) leads to damage and
degradation of collagen.
42,43
Adjunctive Skin Care 227
Mechanisms by which an improvement in lines
and wrinkles can be achieved include the upregu-
lation of collagen production coupled with the
down-regulation of collagen degradation, with
dermal fibroblasts being the target cell in this
strategy. To this end, peptides (short chains of
amino acid sequences) have been incorporated
into cosmeceuticals to stimulate collagen produc-
tion. Peptides can be subdivided into three
categories:
1. Signal peptides
2. Carrier peptides
3. Neurotransmitter-inhibiting peptides.
Perhaps the most studied signal peptide is the
five-amino-acid sequence Lys-Thr-Thr-Lys-Ser
(KTTKS), which is found on type I procollagen
and has been shown to increase the production
of extracellular matrix proteins
44
through the feed-
back regulation of collagen synthesis. Improved
delivery of this hydrophilic peptide has been
accomplished by adding palmitoyl, a 16-carbon
fatty acid fragment, resulting in a compound
known as Pal-KTTKS or, its commercial name,
Matrixyl and is found in several commercially avail-
able products.
An example of a carrier peptide is the tripeptide
glycyl-l-histidyl-l-lysine (GHK), which has been
shown to facilitate copper uptake by cells
45
and
to stimulate fibroblast collagen synthesis.
46
Addi-
tional effects of GHK include dermal remodeling
by increasing levels of MMP-2 and MMP-2 mRNA
and increasing levels of tissue inhibitors of metallo-
proteinase 1 and 2,
47
increases in type I collagen
and glycosaminoglycans,
48
and increases in der-
matan sulfate and cell layer-associated heparin
sulfate.
49
In vitro studies have shown that acetyl
hexapeptide-3, also known as argireline, functions
as a neurotransmitter inhibiting peptide by inter-
fering with sensory nerve action potential-25,
50
thus mimicking the effects of clostridial botulinum
neurotoxin. Although there is in vitro evidence of its
ability to inhibit acetylcholine release, in vivo
studies are limited, probably because of the
inability of this compound to penetrate to the
muscle. Nonetheless, argireline has been incorpo-
rated into several cosmeceutical products.
Additional peptides include tripeptide-1 (Alde-
nine), which acts by reducing glycation and
advanced glycation end products by increasing
superoxide dismutase and decreases collagen
cross-linking and other peptides, and palmitoyl
tetrapetide-7 and palmitoyl oligopeptide (together
known as Matrixyl 3000), which act to stimulate
type I collagen, fibronectin, and hyaluronic acid.
Additional peptides will be covered under the topic
of puffiness and dark circles.
Growth factors
Growth factors are high molecular weight peptides
that regulate specific cellular activities, including
tissue repair and growth and intercellular signaling.
There is evidence to suggest that the following
play a role in skin rejuvenation
51
:
TGF
Epidermal growth factor
Platelet-derived growth factor
Insulin-like growth factor
Fibroblast growth factor
Vascular endothelial growth factor (VEGF).
A double-blind study involving 60 subjects
examined the safety and efficacy of a proprietary
mixture of more than 110 growth factors, cyto-
kines, and soluble matrix proteins secreted by
human fibroblasts in the treatment of mild to severe
photodamage. Patients were randomized to
receive either the active gel or the vehicle and
were instructed to apply it twice daily. Both subjec-
tive and objective measurements at 3 months
showed a greater reduction in fine lines and wrin-
kles by the active gel when compared with the
vehicle, suggesting that a topical gel of growth
factors and cytokines can improve the signs of
photoaging
52
when used with a sunscreen.
Alternatives to human growth factors are those
derived from plants, such as N-furfuryladenine,
and animal-derived growth factors, such as snail
secretion filtrate, the most biologically active of
which is derived from Cryptomphalus aspersa
(SCA). This compound has been used successfully
in Europe for over 15 years to treat radiation
dermatitis.
53,54
SCA is found in commercially avail-
able products used to treat the signs of photoag-
ing and at least one published study has
demonstrated its efficacy in the treatment of peri-
ocular wrinkles.
55
DNA repair liposomes have been shown to
reduce the incidence of UV-induced skin cancer
in mice,
56
although to date, there are no controlled
clinical studies in humans demonstrating the
same. Despite the lack of clinical studies, incorpo-
ration of these compounds into antiaging products
is becoming increasingly popular, and the author is
aware of some ongoing studies involving some of
the commercially available products.
DNA repair enzymes include photosomes, which
are a plankton-derived form of photolyase and
block the transcription of UV-induced pyrimidine
dimers, roxisomes or oxoguanine glycosylase-1;
a mitochondrial DNA repair enzyme obtained from
the Arabidopsis thaliana (mustard) plant, which
Bucay & Day
228
serves to excise damaged DNA; and ultrasomes, or
T4 endonuclease, which is derived from Micro-
coccus lysate and acts by excising UV-induced
dimers. Liposomal formulation of these enzymes
allows for targeted delivery and enhanced efficacy.
Photobiologist and cosmeceutical innovator Daniel
Yarosh, PhD, has published more than 100 articles
on the subject of DNA repair; his book, The New
Science of Perfect Skin, is an excellent reference
on the science of skin care.
57
Stem cells are a hot topic in many areas of medi-
cine and their incorporation into skin care is an
emerging trend. Plant stem cells, such as apple
stem cells, can be found in currently available
skin care products; however, the inclusion of
autologous human cells in skin care heralds the
latest advance in the treatment of photodamage.
An additional application of the recent FDA
approval of technology involving the injection of
an autologous fibroblast suspension for the treat-
ment of fine lines and wrinkles will extend to the
use of these same cells to formulate personalized
skin care. Controlled clinical trials will be neces-
sary to prove their efficacy.
Complications with Peptides and Growth
Factors
A theoretical complication associated with the use
of human growth factors is the development of
skin cancers or the progression of precancerous
lesions to skin cancer in susceptible or predis-
posed individuals. Vivian W. Bucay emphasize
that the potential for skin cancer is theoretical
and based on personal experience (the develop-
ment of actinic keratoses and/or squamous cell
skin cancer in one author and four others following
use of a cosmeceutical containing VEGF) and that
there are no reports in the literature documenting
the development of skin cancer associated with
cosmeceutical use.
This discussion is limited to VEGF and its effect
on skin cancer development because there are
ample references in the literature regarding the
subject. Research shows that levels of VEGF are
at least 10 times higher in patients with mela-
noma.
58,59
Melanoma cells express receptors for
various growth factors, such as VEGF, and
increased angiogenesis secondary to excessive
VEGF exposure has been shown to be a funda-
mental step in the transition of dormant tumors
to malignancies.
60–62
The role of VEGF in mela-
noma is discussed because melanoma is the
deadliest form of skin cancer, although not
the most common. Squamous cell carcinoma is
the second most common skin cancer,
63
and
important progress regarding the role of VEGF in
tumor initiation and progression has been made.
Cancer stem cells have been described in several
cancers, including cutaneous squamous cell
tumors.
64
Through work on defining the mecha-
nism of action of VEGF-targeted therapies, it is
known that VEGF exerts its effects on tumors not
only through angiogenesis but also via a direct
effect on tumor cells.
65
Using a mouse model for
squamous cell tumors (considered ideal for
studying skin cancer initiation and growth
66
),
Beck and colleagues
67
delineated the dual role of
VEGF in regulating the initiation and stemness
(the ability of cancer stem cells to renew and differ-
entiate themselves). They showed that VEGF
promotes cancer stemness and symmetric cancer
stem cell division via neurolipin-1 (Nrp1), a VEGF
coreceptor expressed in cutaneous cancer stem
cells and the deletion of Nrp1 in normal epidermis
prevented skin tumor initiation.
VEGF is upregulated by UVB exposure from
sunlight,
68
adding to the susceptibility of unpro-
tected skin. Patients are often reluctant to apply
sunscreen to the eyelids and periorbital region,
citing such reasons as burning, stinging, and
tearing of the eye area. It is the authors’ opinion
that, although cosmeceutical products containing
human growth factors are not subject to the
same testing and FDA regulations as prescription
drugs are, there is still much to be learned and
understood regarding their mechanism of action
and caution should be exercised when used in
patients with a high risk or history of skin cancer.
INFRAORBITAL DARK CIRCLES AND
PUFFINESS
Compared with the extensive research that
contributes to our understanding regarding the
mechanisms that lead to photoaging, there is
a relative paucity of scientific information regarding
the causes of under-eye puffiness and dark circles,
which cannot be studied via animal models and
tissue cultures. For this reason, the underlying
causes of these common complaints are dis-
cussed here in terms of contributing anatomic
and physiologic considerations.
Although not a condition associated with
morbidity, dark circles are often a source of
cosmetic concern that can have a negative impact
on an individual’s quality of life
68
because they can
convey a sense of sadness or fatigue, even when
these are not the case. Causes of dark circles
are numerous and usually not limited to a single
factor in a given individual and include excessive
pigmentation, thin and translucent eyelid skin,
shadowing secondary to skin laxity, and anatomic
Adjunctive Skin Care 229
age-related changes leading to hollowing and tear
trough deformity.
69,70
Excessive Pigmentation
Excessive pigmentation may be caused by under-
lying dermal melanocytosis,
71
which may also be
attributed to congenital causes, such as nevus of
Ota,
72
sun exposure, drug ingestion,
73
or medical
conditions including atopic or contact dermatitis
that leads to rubbing or scratching of the periorbital
region with the development of postinflammatory
hyperpigmentation.
69
Hemosiderin deposition due
to “leaky” vasculature or following trauma may
also cause pigmentary changes in the lower eye-
lids. Depending on the underlying cause and the
depth of pigmentation, treatment options may
include topical prescription medications to treat
an underlying medical problem, laser modalities,
chemical peels, and/or cosmeceutical agents.
As already mentioned, the eyelids have the thin-
nest skin of the body, and the orbicularis oculi
muscle lies just beneath the eyelid skin with
minimal subcutaneous fat found between the
muscle and skin. This is a contributing factor to
the appearance of dark circles. A prominent subcu-
taneous and/or muscular vascular plexus will result
in a violaceous hue under the eyes that does not
blanch but deepens in color with manual stretching
of the skin.
74
This maneuver of stretching the skin
to produce deepening of the violaceous color
may serve as useful diagnostic tool to confirm the
vascular cause of the pigmentation.
69
Moreover,
in their review on this subject, Roh and Chung
69
state that the successful use of autologous fat
transplantation to reduce the appearance of hyper-
vascularity supports the idea that it is the vascula-
ture found within the muscle instead of the
combination of thin skin and subcutaneous vascu-
larity that plays a greater role in the appearance of
these violaceous infraorbital dark circles.
In addition to autologous fat transplantation,
various modalities, including laser and other
energy-based devices as well as soft tissue fillers,
have been tried with varying success. In keeping
with the theme of adjunctive skin care of the
eyelids, topical agents that exert effects on the
vasculature will be discussed, although, as is the
case with many cosmeceuticals, controlled clinical
studies to support their use are lacking.
Shadowing
Shadowing due to intrinsic and extrinsic aging of
the skin that leads to skin laxity,
75
in combination
with age-related changes in the soft tissue and
skeleton, is another common cause of dark circles.
The appearance of a “tear trough” depression
secondary to loss of subcutaneous fat and
thinning of the skin over the orbital rim ligament
leads to hollowing of the orbital rim,
76
leading to
a dark shadow that can be further accentuated
by pseudoherniation of the infraorbital fat pad.
77
Short of addressing the issue of photodamaged
skin as discussed earlier in this article, adjunctive
skin care does not play a role in the treatment of
this type of infraorbital dark circle.
Puffiness and bags
Under-eye puffiness and lower eyelid bags are also
multifactorial in origin and another common aesthetic
complaint, although published studies regarding this
topic are scarce. In an analysis of 114 consecutive
subjects (67 men and 47 women, mean age 52 years,
age range 23–76 years) presenting for aesthetic
consultation for lower eyelid bags, Goldman and
colleagues
77
conclude that there is not a single
anatomic basis for their cause but, instead, identify
six anatomic variables. These include
1. Cheek descent and hollow tear trough (52%)
2. Prolapsed of orbital fat (48%)
3. Skin laxity and sun damage (35%)
4. Eyelid fluid (32%)
5. Orbicularis hyperactivity (20%)
6. Triangular cheek festoon (13%).
Not surprising, tear trough depression, skin laxity,
and triangular malar mound occurred with greater
frequency in those older than 50 years, and linear
regression analysis showed that a recommendation
for surgery was based on the extent of fat prolapse,
skin elasticity, and midface descent.
Surgical intervention, laser resurfacing,soft tissue
fillers,
78
neurotoxins, and energy-based skin tight-
ening may be used in varying combinations to
address this complaint. Nonetheless, despite the
evidence in support of an anatomic basis for
under-eyepuffiness and bags, patients seek recom-
mendations for cosmeceuticals that can diminish
their appearance. Most products used for this indi-
cation contain ingredients to reduce fluid retention,
strengthen the vasculature, and improve skin laxity.
SKIN CARE INGREDIENTS FOR DARK CIRCLES
AND PUFFY EYES
An Internet search for products for “dark circles and
puffy eyes” yielded 621,000 results, a testament to
the vast array of skin care products devoted to the
treatment of these common problems. The lack of
controlled trials precludes an evidence-based
approach and much of the available information
regarding the efficacy of these skin care products
is anecdotal and largely dependent on testimonials
and marketing campaigns. In preparing this article,
several ingredients were noted to be incorporated
Bucay & Day
230
Table 1
Physician Dispensed Eye Creams
HydroPeptide Eye (Azure, Issaquah, WA)
Key ingredients: Haloxyl (palmitoyl oligopeptide, palmitoyl tetrapeptide-7, chrysin and
N-hydroxysuccinimide), Eyeliss (dipeptide-2), vitamin K, Syn-coll (palmitoyl tripeptide-5), Matrixyl
3000 (palmitoyl tetrapeptide-7, palmitoyl oligopeptide), Dermaxyl (palmitoyl oligopeptide),
Aldenine (tripeptide-1), Argireline (acetyl hexapeptide-8), hesperidin methyl chalcone, retinyl
palmitate, green tea, sodium hyaluronate
Indications: photoaging, dark circles, puffiness
Gloss Dual-Treatment Eye Area (Young Pharmaceuticals, Hartford, CT)
Key ingredients:
STT Eye Area Restorative Eye Cream: 0.5% trichloroacetic acid, vitamin C ester, vitamin E ester,
ferulic acid ester, green tea extract, hesperidin methyl chalcone, niacinamide, 18-beta-glycyrrhe-
tinic acid (licorice), Argireline (acetyl-hexapeptide-8), Granactive AGE (palmitoyl hexapeptide-14),
Chronoline (caprooyl tetrapaptide-3), B-White (oligopeptide-68)
MWF Retinol Eye Area: Retinol EmoluGel microsponge
Indications: photoaging, dark circles, puffiness
CELFIX DNA iQuad Infusion Total Eye Complex (PrecisionMD, NY, NY)
Key ingredients: Haloxyl (palmitoyl oligopeptide, palmitoyl tetrapeptide-7, chrysin,
N-hydroxysuccinimide), Matrixyl 3000 (palmitoyl tetrapeptide-7, palmitoyl oligopeptide), photolyase
liposomes, caffeine, ubiquinone, grape seed oil, green tea extracts, ivy extract, sodium hyaluronate,
plankton extract
Indications: photoaging, dark circles, puffiness
Tensage Eye Contour (Biopelle, Ferndale, MI)
Key ingredients: 8% SCA (snail secretion filtrate) derived from Cryptomphalus aspersa
Indication: photoaging
NeoStrata SKIN ACTIVE Intensive Eye Therapy (Neostrata Co, Inc., Princeton, NJ)
Key ingredients: NeoGlucosamineÔ(melanin production inhibitor), palmitoyl oligopeptide, palmitoyl
tetrapeptide-7, tocopheryl acetate (vitamin E), sodium hyaluronate, caffeine, Malus domestica fruit
cell culture extract (apple stem cell extract)
Indications: photoaging, dark circles, puffiness
Revale
´Skin Replenishing Eye Therapy
Key ingredients: 1% CoffeBerry extract
Indications: photoaging, puffiness
Lumie
`re Riche Bio-restorative Eye Balm (NEOCUTIS, Inc. San Francisco, CA)
Key ingredients: PSP
Ò
(purified skin proteins- a mixture of human growth factors, cytokines, and
interleukins), caffeine, hyaluronic acid
Indications: photoaging, dark circles, puffiness
ELASTIdermÔEYE Complete ComplexÔSerum (Obagi Medical Products, Long Beach, CA)
Key ingredients: caffeine, malonic acid, arginine
Indications: photoaging, puffiness
Replenix
Ò
Eye Repair Cream (Topix Pharmaceuticals, Inc., N. Amityville, NY)
Key ingredients: all-trans-retinol, green tea polyphenols, Arnica montana, phytonadione (vitamin K),
hesperidin methyl chalcone, sodium hyaluronate, dipeptide-2, N-hydroxysuccinimide, chrysin,
palmitoyl oligopeptide, palmitoyl tetrapeptide-7
Indications: photoaging, dark circles, undereye puffiness
Pro+Therapy MDÔUltimate Lift + Correcting Eye Cream (Valeant Pharmaceuticals, Bridgewater, NJ)
Key ingredients: kinetin (0.1%)-Zeatin (0.1%) Complex; Eye Regener
Ò
(a registered trademark of Silab,
Brive Cedex, France)- derived from white lupine and alfalfa seed, acts to enhance lymphatic drainage;
Intensyl
Ò
(a registered trademark of Silab, Brive Cedex, France)- hydrolyzed Manihot esculenta tuber
extract, 3-D glucan biopolymer acts to smooth and lift skin within 10 minutes
Indications: photoaging, puffiness
(continued on next page)
231
Adjunctive Skin Care
into many of the product lines researched for this
topic. This list is by no means exhaustive and, for
the sake of simplicity, ingredients are listed under
the heading that best describes the underlying
cause/targeted problem:
Puffiness
Epilobium angustifolium extract (willow herb):
antimicrobial, anti-irritant and antiinflammatory
properties
Dipeptide-2: also known as Eyeliss; improves
lymphatic circulation and drainage; inhibits
angiotensin-converting enzyme (ACE);
strengthens capillaries
Hesperidin methyl chalcone: improves vascular
integrity by strengthening capillaries; decreases
capillary permeability
Caffeine: antioxidant, anti-irritant, purported to
decrease fat when applied topically
Green tea and coffeeberry polyphenols: antioxi-
dant, antiinflammatory, anti-irritant
Palmitoyl tetrapeptide-7: peptide that improves
skin elasticity, firmness, and tone by increasing
collagen, hyaluronic acid, and fibronectin
Palmitoyl oligopeptide: also known as Dermaxyl;
boosts cell communication and dermal repair
mechanisms
Palmitoyl tripeptide-5: also known as Syn-Coll;
increases collagen 1 production via TGF-b;
reportedly 60% more effective than palmitoyl
pentapeptide
Hyperpigmentation (Melanin)
Arbutin: from bearberry; precursor of
hydroquinone
Hydroquinone: decreases melanin synthesis by
blocking tyrosinase
Kojic acid: byproduct of fermentation process in
malting rice used in sake production; decreases
melanin production; unstable compound so
a more stable kojic dipalmitate is often used in
skin care products but may not be as effective
Vitamin C: antioxidant and antiinflammatory;
reduces hyperpigmentation and increases
collagen production; forms of vitamin C include
ascorbic acid, magnesium ascorbyl phosphate,
L-ascorbic acid, THD, ascorbyl palmitate, ascorb-
yl glucosamine, sodium ascorbyl phosphate, as-
corbyl glucoside, and ascorbyl tetraisopalmitate.
Soy: antioxidant and antiinflammatory; inacti-
vates keratinocyte cell receptors that mediate
transfer of melanosomes from melanocytes to
keratinocytes
Niacinamide (vitamin B3): antioxidant and antiin-
flammatory; increases levels of free fatty acids
and ceramides in the skin and decreases trans-
epidermal water loss; improves hyperpigmenta-
tion by decreasing melanosome transfer from
the melanocyte to the keratinocyte.
Retinol (retinaldehyde, retinyl palmitate):
increases cell turnover; inhibits tyrosinase to
decrease melanin production
Azelaic acid: tyrosinase inhibitor
Lignin peroxidase: enzyme derived from the tree
fungus Phanerochaete chrysosporium that breaks
down lignin(found in tree bark); also breaks down
melanin, which is structurally similar to lignin
Vascular Pigmentation
Chrysin: involved in the clearance of bilirubin,
a breakdown product of hemoglobin
N-hydroxysuccinimide: increases the elimination
of hemoglobin breakdown products and
increases clearance of iron by rendering it soluble
Vitamin K: antiinflammatory effects as well as
effects on circulation and/or clotting
Chrysin, N-hydroxysuccinimide, palmitoyl
tetrapeptide-3, palmitoyl oligopeptide: this
combination is known as Haloxyl. Please refer
to Table 1 for a list of physician dispensed eye
creams that contain some of the key ingredients
listed below.
EYELASHES AND EYEBROWS
A thorough discussion regarding adjunctive skin
care of the periorbital region should include
a mention of eyelash and eyebrow enhancing
agents. Since its approval by the FDA in December
2008, the only FDA-approved agent for the
enhancement of eyelash growth is bimatoprost
ophthalmic solution 0.03%, although countless
over-the-counter products that claim to enhance
Table 1
(continued)
MEG 21 EYE TREATMENT (Dynamis Skin Science, Inc., Jenkintown, PA)
Key ingredients: Supplamine
Ò
, which is a patented combination of N-Methyl-D-glucamine (meglumine)
and arginine. Meglumine inhibits glycation and arginine inactivates glycation byproducts; also
contains anti-inflammatory botanical extracts
Indications: photoaging, dark circles, puffiness
Bucay & Day
232
eyelashes and eyebrows can be found in a variety
or retail outlets ranging from drugstores to
high-end department stores. Several skin care
companies also manufacture lash-enhancing and
brow-enhancing products for office dispensing.
The mechanism of action by which bimatoprost
improves lash growth is not completely under-
stood but is thought to involve an increase in the
percentage of eyelash follicles in anagen, which
may account for increased eyelash length. Bima-
toprost also exerts a stimulatory effect on melano-
genesis, which may result in darker lashes.
Increased lash thickness and fullness may be
due to an increase in size of the hair bulb and
dermal papilla.
79
Its safety, efficacy, and tolera-
bility are well documented.
80,81
The successful use of bimatoprost for eyelash
enhancement has led to its off-label use to treat
eyebrows and, in the experience of the authors,
is something often initiated by the patient with
successful results. Although not FDA-approved
for this purpose, a recent publication seems to
support the use of bimatoprost ophthalmic solu-
tion 0.03% for eyebrow growth.
82
Side Effects of Lash Growth Products
Side effects of lash-enhancing products include
itchy eyes, redness of the eyes, temporary hyper-
pigmentation of eyelid skin, and hair growth in
other areas that come into contact with the
product. Please refer to the Latisse product insert
for a complete list of side effects, including the risk
of developing brown hyperpigmentation of the iris,
which was reported with the use bimatoprost solu-
tion used intraocularly for glaucoma.
Patient Expectations Compared with Results
of Using Adjunctive Skin Care and Lash
Growth Products
In the authors’ view, patients want and may even
expect surgical results from a topically applied
product. It is important to set realistic expectations
regarding the role of adjunctive skin care and lash
growth products. With the exception of topical
prescription retinoids and a prescription lash
growth product, there is a paucity of controlled
clinical studies that prove the benefits and efficacy
of topical cosmeceutical preparations, which is
not to say that there is not scientific evidence
underlying the rationale for their use.
Signs of early photodamage, such as fine lines
and shallow wrinkles, often respond to topically
applied products, provided that the patient is
compliant regarding sun protection and uses the
product consistently. In moderate-to-severe
cases of photodamage, resurfacing procedures,
such as chemical peels or laser resurfacing, may
be more adequate. Treatment of dynamic rhytids
is better addressed by neuromodulators. In many
cases, a combination approach is the most appro-
priate approach to treating the signs of photodam-
age. In this setting, adjunctive skin care is used for
maintenance.
Without controlled studies, the use of topical
antioxidants, growth factors, peptides, and DNA
repair enzymes is based more on their potential
benefits and not proof. Monitoring of patients
and the reporting of any complications, such as
skin cancer, may be indicated, even for cosme-
ceuticals. Realistically, this may be difficult, given
that many of these products are recommended
and dispensed by nonmedical personnel, such
as an aesthetician, in the setting of the physician’s
office, a medical spa, or a retail outlet.
Products targeting infraorbital dark circles and
puffiness may be effective in mild cases. An under-
standing of the underlying causative factors is
needed to guide treatment. In some instances,
fillers or energy-based devices using radiofre-
quency or high-density focused ultrasound may
be a better option; in others, surgery may be the
best treatment.
Even in the setting of the initialvisit, the authors do
not hesitate to refer a patient for surgery when indi-
cated. Patients appreciate candor and honesty and
will be happy to return for maintenance, whether it is
skin care, botulinum toxin, fillers, chemical peels,
laser resurfacing, or energy-based therapies.
SUMMARY
An aging population and the availability and
acceptance of surgical procedures to treat the
signs of aging of the periorbital area have been
accompanied by the development of minimally
invasive aesthetic procedures for rejuvenation of
this region. A deeper understanding of the contrib-
utory anatomic and physiologic factors underlying
common cosmetic concerns, such as fine lines
and wrinkles, under-eye dark circles, and under-
eye puffiness, has allowed us to tailor treatments
to the individual’s needs.
A parallel explosion in the skin care industry,
particularly in the arena of cosmeceuticals, has
added to the palette of resources available to
address these common cosmetic concerns. UV
radiation is the number one cause of photodam-
age, making sun protection the pillar of any
adjunctive skin care regimen. That said, a skin
care regimen consisting of topically applied reti-
noids, antioxidants, collagen boosters, and DNA
repair enzymes may be useful as a stand-alone
treatment or as maintenance therapy, whether
Adjunctive Skin Care 233
following surgery or one of the many minimally
invasive cosmetic procedures.
Most importantly, treating cosmetic concerns
does not exempt dermatologists from keeping in
mind the patient’s medical history. In the context
of human growth factors, there is still much to be
learned regarding the potency of some of these
“hot” compounds foundin some skin care products
and the theoretical, but possible, complicationsthat
may arise from their use in a susceptible individual.
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