A d j u n c t i v e S k i n C a re o f t h e

B row a n d Per ior b it al Region

Vivian W. Bucay, MDa,b,*, Doris Day, MD, MAc,d

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.

INTRODUCTION FINE LINES AND WRINKLES

The periorbital region is often one of the first areas Eyelid skin is the thinnest in the body, at times only
to show signs of aging and patients seek a derma- 0.2 mm thick, contributing to its susceptibility to
tologist’s advice regarding care of the eyelid skin, actinic and other damage. UV radiation is the
often starting in their early 20s, well before seeking primary cause of photodamage resulting in fine
other antiaging treatments. In the context of lines, mottled pigmentation, and textural changes.
a multidisciplinary approach to brow and eyelid Other factors that lead to skin changes include
rejuvenation, it is the dermatologist’s responsibility genetic predisposition, smoking, and chronic
to be familiar with the many skin care options avail- rubbing due to seasonal allergies, irritants, or
able for common concerns, including fine lines and contact dermatitis. Components of adjunctive
wrinkles, infraorbital dark circles, and under-eye skin care to treat the signs of photodamage may
puffiness. Eyelid anatomy and aging are ad- include sunscreen, topical antioxidants, retinoids,
dressed in elsewhere in this issue by Lam and collagen boosters, and DNA repair.
colleagues, Fitzgerald, Pepper and Moyer, Lee
and Baker, Quatela and Lieberman, Day and
Sunscreens
Bucay, and Sundaram. They are also discussed
in this article as they concern some key concepts Sunscreens are an indispensable element of
relevant to understanding the aforementioned adjunctive skin care of the eyelids and periorbital
plasticsurgery.theclinics.com

common complaints. 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: [email protected]

Clin Plastic Surg 40 (2013) 225–236

http://dx.doi.org/10.1016/j.cps.2012.09.003
0094-1298/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved.
226 Bucay & Day

sunscreens should offer broad UV protection to collagen production and has been shown to stim-
include UVA (320–400 nm) and UVB (290–320 nm) ulate collagen production when added to cultures
and are integral in preventing UV immunosuppres- of human skin fibroblasts.11 Vitamin C also
sion.1 They should contain only ingredients that restores the antioxidant capacity of vitamin
have been approved by the US Food and Drug E,12,13 a much more potent inhibitor of lipid
Administration (FDA) as listed in the FDA’s peroxidation.
Sunscreen Monograph Final Rule.2 Sunscreens
are generally divided into two classes: Vitamin E
Vitamin E is lipid soluble and consists of eight
1. Chemical—organic active isomers (tocopherols and tocotrienols),
2. Physical—inorganic. with alpha-tocopherol showing the most biologic
activity. Vitamin E reduces the number of sunburn
Chemical sunscreens (eg, benzophenone, ho-
cells, decreases UVB-induced photodamage,14
mosalate, methyl anthranilate, octyl methoxycin-
and can inhibit UV-induced tumor formation.15
namate, oxybenzone, avobenzone) work by
Alpha-tocopherol, a membrane-bound antioxi-
converting UVB radiation into heat, whereas phys-
dant, protects cell membranes from damage
ical sunscreens (eg, zinc oxide, titanium dioxide,
caused by phospholipase A, lysophospholipids,
kaolin, ichthammol, iron oxide) scatter, reflect
and free fatty acids.14 Vitamin E has been shown
and absorb solar radiation across a broad spec-
to inhibit human macrophage metalloelastase,
trum in the UV and visible ranges. In addition to
a matrix metalloproteinase (MMP) that degrades
their greater chemical stability, physical sun-
elastin.15 Furthermore, signs of photoaging were
screens have the added benefit of a minimal risk
shown to improve in a study comparing the use
of contact sensitivity, an important consideration
of a vitamin E cream versus placebo.16
for delicate eyelid skin.
Combined vitamins C and E
Topical Antioxidants The combined application of Vitamins E and C that
is commercially available in several product lines
Topical antioxidants scavenge free radicals, which has been shown to provide more potent photopro-
are highly unstable and reactive molecules. Free tection compared with either agent alone.6 A limi-
radicals that are generated from oxygen are known tation to topically applied vitamin E is the potential
as reactive oxygen species. Capable of damaging for contact dermatitis.17,18
cellular membranes, DNA, and cellular proteins,
free radicals can be produced by normal cellular Green tea
metabolism or can be triggered by external factors, Green tea antioxidants extracted from the leaves
including UV radiation and cigarette smoking. Skin and buds of the plant Camellia sinensis include epi-
aging is generally attributed to a combination of catechin, epicatechin-3-gallate, epigallocatechin,
intrinsic and/or chronologic aging and extrinsic and epigallocatechin-3-gallate (EGCG), the latter
and/or environmental aging, and reactive oxygen being the most abundant and potent.19 Animal
species play a key role in both types of aging, studies have shown that topically applied green tea
a concept first published by Harman3 in 1956. polyphenols can inhibit photocarcinogenesis20 as
Free radicals can also lead to inflammation, well as prevent UV-induced oxidative damage and
another factor that has been implicated in the aging induction of MMPs.21 In vivo application of green
process.4 tea polyphenols to human backs 30 minutes before
UV irradiation was shown to reduce erythema, the
Vitamin C number of sunburn cells, immunosuppression,22
Topical vitamin C (ascorbic acid) has been shown and DNA damage.23 Another study demonstrated
to reduce UV-induced erythema, sunburn cell the efficacy of topically applied EGCG in reducing
formation,5,6 and the appearance of wrinkles.7,8 UVB-induced inflammation.24 Although controlled
A combination of topically applied water soluble clinical trials are lacking, green tea polyphenols are
vitamin C (ascorbic acid), and a lipid soluble popular in cosmeceuticals given their ability to multi-
form, tetrahexyldecyl ascorbate (THD), has also task. Vivian W. Bucay find them very helpful in miti-
been shown to reduce wrinkling due to photodam- gating the retinoid-induced irritation.
age.9 Studies have shown that, at the same
concentration, THD surpasses the depth of pene- Vitamin B3
tration of ascorbic acid by threefold and that its Topically applied niacinamide, the biologically
rate of penetration is greater, even when the active form of vitamin B3, not only exhibits antiox-
concentration of ascorbic acid is 25 times that of idant and antiinflammatory properties25 but also
THD.10 Vitamin C plays an important role in can improve hyperpigmentation by decreasing
 Adjunctive Skin Care 227

transfer of melanosomes to keratinocytes. The acid.38 Eye skin care products containing hyalur-
effects of topically applied niacinamide include onic acid, ceramides, cholesterol, and dimethyla-
improved skin texture and tone along with a reduc- minoethanol (DMAE) lactate are useful in
tion in fine lines and hyperpigmentation.26 mitigating dryness and skin irritation, and main-
taining an adequate skin barrier.
Side Effects of Topical Antioxidants
Side effects associated with topical antioxidants Side Effects of with Retinoids
may include allergic contact dermatitis or irritant
dermatitis. Topical vitamin E and niacinamide The most common side effect associated with reti-
may induce allergic contact dermatitis, whereas noid use is an irritant dermatitis, characterized by
irritant dermatitis may occur with some forms of excessive redness, dryness and flaking. This can
topical vitamin C, such as the water-soluble forms, be minimized by selecting the appropriate type
because higher concentrations are required for of retinoid for the patient’s skin type, for example,
efficacy. retinoic acid or retinol for someone with thicker,
oilier skin and retinaldehyde for those with thinner,
Retinoids drier skin. Additional strategies for mitigating skin
irritation include decreasing the amount of product
Retinoids are a classification of naturally occurring
applied and/or the frequency of application. Layer-
and synthetic compounds that exhibit the biologic
ing the retinoid over a product containing antiin-
actions of vitamin A. Their inclusion in countless
flammatory ingredients such as green tea
antiaging products was triggered by Kligman and
polyphenols or coffeeberry also reduces skin irrita-
colleagues’27 groundbreaking research on the
tion. Protective measures regarding sun exposure
effects of tretinoin on photodamaged skin in 1986.
are strongly recommended and include
Prescription retinoids sunscreen, sunglasses, and hats.
Of the prescription retinoids, only tretinoin and ta- Patients should be counseled against using
zarotene have FDA approval for the treatment of prescription retinoids during pregnancy and lacta-
photodamage, although nonprescription retinol tion. The authors recommend that each patient
and retinaldehyde are commonly used for this indi- consult her obstetrician regarding the use of
cation. Wrinkle improvement is the result of nonprescription retinoids during pregnancy and
retinoid-mediated effects that produce an increase lactation.
in dermal collagen synthesis by increasing type I
procollagen expression28 mediated by the inhibi-
Collagen Boosters: Peptides and Growth
tion of the UV-induction of c-Jun29 and an alteration
Factors
of transforming growth factor (TGF)-b expression.30
Inhibition of dermal collagen degradation is Peptides
accomplished by inhibition of transcriptional factor Collagen boosters typically include compounds
activator protein-1 activation of MMP-like such as peptides and growth factors. A brief
collagenase.31,32 review of the pathogenesis of aging skin will aid
Retinoids also improve dyschromia by inhibiting in understanding the rationale for the use of these
tyrosinase activity. This leads to a reduction of compounds in antiaging products:
melanin synthesis, decrease in melanosome trans-
fer, and increase in shedding of keratinocytes.33,34  Lines and wrinkles occur both in photoaged
Additionally, retinoids contribute to smoother skin and chronologically aged skin
and a reduction in tactile roughness by increasing  Coarser lines and wrinkles are character-
epidermal proliferation and differentiation, com- istic of photoaging, whereas finer lines are
pacting the stratum corneum, and increasing more typical of chronologic aging
epidermal and dermal intercellular mucin  The pathogenesis of skin aging is charac-
deposition.35,36 terized by a decrease in collagen synthesis
coupled with an increase in collagen
Over-the-counter retinoids breakdown39
Over-the-counter alternatives include retinol that,  A decrease in procollagen type I mRNA is
although potentially less irritating than its metabo- seen in aging skin,40 with a greater reduc-
lite retinoic acid (tretinoin), is also 20-fold less tion seen in photodamaged skin compared
potent.36 Retinaldehyde, a naturally occurring with nonexposed skin41
metabolite of retinol and the precursor of retinoic  UV radiation–induced upregulation of colla-
acid, has demonstrated efficacy in treating photo- genase (MMP-1) leads to damage and
damage37 but with less irritation than retinoic degradation of collagen.42,43
228 Bucay & Day

Mechanisms by which an improvement in lines Additional peptides will be covered under the topic
and wrinkles can be achieved include the upregu- of puffiness and dark circles.
lation of collagen production coupled with the
down-regulation of collagen degradation, with Growth factors
dermal fibroblasts being the target cell in this Growth factors are high molecular weight peptides
strategy. To this end, peptides (short chains of that regulate specific cellular activities, including
amino acid sequences) have been incorporated tissue repair and growth and intercellular signaling.
into cosmeceuticals to stimulate collagen produc- There is evidence to suggest that the following
tion. Peptides can be subdivided into three play a role in skin rejuvenation51:
categories:  TGF
 Epidermal growth factor
1. Signal peptides  Platelet-derived growth factor
2. Carrier peptides  Insulin-like growth factor
3. Neurotransmitter-inhibiting peptides.  Fibroblast growth factor
 Vascular endothelial growth factor (VEGF).
Perhaps the most studied signal peptide is the
five-amino-acid sequence Lys-Thr-Thr-Lys-Ser A double-blind study involving 60 subjects
(KTTKS), which is found on type I procollagen examined the safety and efficacy of a proprietary
and has been shown to increase the production mixture of more than 110 growth factors, cyto-
of extracellular matrix proteins44 through the feed- kines, and soluble matrix proteins secreted by
back regulation of collagen synthesis. Improved human fibroblasts in the treatment of mild to severe
delivery of this hydrophilic peptide has been photodamage. Patients were randomized to
accomplished by adding palmitoyl, a 16-carbon receive either the active gel or the vehicle and
fatty acid fragment, resulting in a compound were instructed to apply it twice daily. Both subjec-
known as Pal-KTTKS or, its commercial name, tive and objective measurements at 3 months
Matrixyl and is found in several commercially avail- showed a greater reduction in fine lines and wrin-
able products. kles by the active gel when compared with the
An example of a carrier peptide is the tripeptide vehicle, suggesting that a topical gel of growth
glycyl-l-histidyl-l-lysine (GHK), which has been factors and cytokines can improve the signs of
shown to facilitate copper uptake by cells45 and photoaging52 when used with a sunscreen.
to stimulate fibroblast collagen synthesis.46 Addi- Alternatives to human growth factors are those
tional effects of GHK include dermal remodeling derived from plants, such as N-furfuryladenine,
by increasing levels of MMP-2 and MMP-2 mRNA and animal-derived growth factors, such as snail
and increasing levels of tissue inhibitors of metallo- secretion filtrate, the most biologically active of
proteinase 1 and 2,47 increases in type I collagen which is derived from Cryptomphalus aspersa
and glycosaminoglycans,48 and increases in der- (SCA). This compound has been used successfully
matan sulfate and cell layer-associated heparin in Europe for over 15 years to treat radiation
sulfate.49 dermatitis.53,54 SCA is found in commercially avail-
In vitro studies have shown that acetyl able products used to treat the signs of photoag-
hexapeptide-3, also known as argireline, functions ing and at least one published study has
as a neurotransmitter inhibiting peptide by inter- demonstrated its efficacy in the treatment of peri-
fering with sensory nerve action potential-25,50 ocular wrinkles.55
thus mimicking the effects of clostridial botulinum DNA repair liposomes have been shown to
neurotoxin. Although there is in vitro evidence of its reduce the incidence of UV-induced skin cancer
ability to inhibit acetylcholine release, in vivo in mice,56 although to date, there are no controlled
studies are limited, probably because of the clinical studies in humans demonstrating the
inability of this compound to penetrate to the same. Despite the lack of clinical studies, incorpo-
muscle. Nonetheless, argireline has been incorpo- ration of these compounds into antiaging products
rated into several cosmeceutical products. is becoming increasingly popular, and the author is
Additional peptides include tripeptide-1 (Alde- aware of some ongoing studies involving some of
nine), which acts by reducing glycation and the commercially available products.
advanced glycation end products by increasing DNA repair enzymes include photosomes, which
superoxide dismutase and decreases collagen are a plankton-derived form of photolyase and
cross-linking and other peptides, and palmitoyl block the transcription of UV-induced pyrimidine
tetrapetide-7 and palmitoyl oligopeptide (together dimers, roxisomes or oxoguanine glycosylase-1;
known as Matrixyl 3000), which act to stimulate a mitochondrial DNA repair enzyme obtained from
type I collagen, fibronectin, and hyaluronic acid. the Arabidopsis thaliana (mustard) plant, which
 Adjunctive Skin Care 229

serves to excise damaged DNA; and ultrasomes, or tumor initiation and progression has been made.
T4 endonuclease, which is derived from Micro- Cancer stem cells have been described in several
coccus lysate and acts by excising UV-induced cancers, including cutaneous squamous cell
dimers. Liposomal formulation of these enzymes tumors.64 Through work on defining the mecha-
allows for targeted delivery and enhanced efficacy. nism of action of VEGF-targeted therapies, it is
Photobiologist and cosmeceutical innovator Daniel known that VEGF exerts its effects on tumors not
Yarosh, PhD, has published more than 100 articles only through angiogenesis but also via a direct
on the subject of DNA repair; his book, The New effect on tumor cells.65 Using a mouse model for
Science of Perfect Skin, is an excellent reference squamous cell tumors (considered ideal for
on the science of skin care.57 studying skin cancer initiation and growth66),
Stem cells are a hot topic in many areas of medi- Beck and colleagues67 delineated the dual role of
cine and their incorporation into skin care is an VEGF in regulating the initiation and stemness
emerging trend. Plant stem cells, such as apple (the ability of cancer stem cells to renew and differ-
stem cells, can be found in currently available entiate themselves). They showed that VEGF
skin care products; however, the inclusion of promotes cancer stemness and symmetric cancer
autologous human cells in skin care heralds the stem cell division via neurolipin-1 (Nrp1), a VEGF
latest advance in the treatment of photodamage. coreceptor expressed in cutaneous cancer stem
An additional application of the recent FDA cells and the deletion of Nrp1 in normal epidermis
approval of technology involving the injection of prevented skin tumor initiation.
an autologous fibroblast suspension for the treat- VEGF is upregulated by UVB exposure from
ment of fine lines and wrinkles will extend to the sunlight,68 adding to the susceptibility of unpro-
use of these same cells to formulate personalized tected skin. Patients are often reluctant to apply
skin care. Controlled clinical trials will be neces- sunscreen to the eyelids and periorbital region,
sary to prove their efficacy. citing such reasons as burning, stinging, and
tearing of the eye area. It is the authors’ opinion
that, although cosmeceutical products containing
Complications with Peptides and Growth
human growth factors are not subject to the
Factors
same testing and FDA regulations as prescription
A theoretical complication associated with the use drugs are, there is still much to be learned and
of human growth factors is the development of understood regarding their mechanism of action
skin cancers or the progression of precancerous and caution should be exercised when used in
lesions to skin cancer in susceptible or predis- patients with a high risk or history of skin cancer.
posed individuals. Vivian W. Bucay emphasize
that the potential for skin cancer is theoretical
and based on personal experience (the develop- INFRAORBITAL DARK CIRCLES AND
ment of actinic keratoses and/or squamous cell PUFFINESS
skin cancer in one author and four others following
use of a cosmeceutical containing VEGF) and that Compared with the extensive research that
there are no reports in the literature documenting contributes to our understanding regarding the
the development of skin cancer associated with mechanisms that lead to photoaging, there is
cosmeceutical use. a relative paucity of scientific information regarding
This discussion is limited to VEGF and its effect the causes of under-eye puffiness and dark circles,
on skin cancer development because there are which cannot be studied via animal models and
ample references in the literature regarding the tissue cultures. For this reason, the underlying
subject. Research shows that levels of VEGF are causes of these common complaints are dis-
at least 10 times higher in patients with mela- cussed here in terms of contributing anatomic
noma.58,59 Melanoma cells express receptors for and physiologic considerations.
various growth factors, such as VEGF, and Although not a condition associated with
increased angiogenesis secondary to excessive morbidity, dark circles are often a source of
VEGF exposure has been shown to be a funda- cosmetic concern that can have a negative impact
mental step in the transition of dormant tumors on an individual’s quality of life68 because they can
to malignancies.60–62 The role of VEGF in mela- convey a sense of sadness or fatigue, even when
noma is discussed because melanoma is the these are not the case. Causes of dark circles
deadliest form of skin cancer, although not are numerous and usually not limited to a single
the most common. Squamous cell carcinoma is factor in a given individual and include excessive
the second most common skin cancer,63 and pigmentation, thin and translucent eyelid skin,
important progress regarding the role of VEGF in shadowing secondary to skin laxity, and anatomic
230 Bucay & Day

age-related changes leading to hollowing and tear thinning of the skin over the orbital rim ligament
trough deformity.69,70 leads to hollowing of the orbital rim,76 leading to
a dark shadow that can be further accentuated
Excessive Pigmentation by pseudoherniation of the infraorbital fat pad.77
Excessive pigmentation may be caused by under- Short of addressing the issue of photodamaged
lying dermal melanocytosis,71 which may also be skin as discussed earlier in this article, adjunctive
attributed to congenital causes, such as nevus of skin care does not play a role in the treatment of
Ota,72 sun exposure, drug ingestion,73 or medical this type of infraorbital dark circle.
conditions including atopic or contact dermatitis Puffiness and bags
that leads to rubbing or scratching of the periorbital Under-eye puffiness and lower eyelid bags are also
region with the development of postinflammatory multifactorial in origin and another common aesthetic
hyperpigmentation.69 Hemosiderin deposition due complaint, although published studies regarding this
to “leaky” vasculature or following trauma may topic are scarce. In an analysis of 114 consecutive
also cause pigmentary changes in the lower eye- subjects (67 men and 47 women, mean age 52 years,
lids. Depending on the underlying cause and the age range 23–76 years) presenting for aesthetic
depth of pigmentation, treatment options may consultation for lower eyelid bags, Goldman and
include topical prescription medications to treat colleagues77 conclude that there is not a single
an underlying medical problem, laser modalities, anatomic basis for their cause but, instead, identify
chemical peels, and/or cosmeceutical agents. six anatomic variables. These include
As already mentioned, the eyelids have the thin-
nest skin of the body, and the orbicularis oculi 1. Cheek descent and hollow tear trough (52%)
muscle lies just beneath the eyelid skin with 2. Prolapsed of orbital fat (48%)
minimal subcutaneous fat found between the 3. Skin laxity and sun damage (35%)
muscle and skin. This is a contributing factor to 4. Eyelid fluid (32%)
the appearance of dark circles. A prominent subcu- 5. Orbicularis hyperactivity (20%)
taneous and/or muscular vascular plexus will result 6. Triangular cheek festoon (13%).
in a violaceous hue under the eyes that does not
blanch but deepens in color with manual stretching Not surprising, tear trough depression, skin laxity,
of the skin.74 This maneuver of stretching the skin and triangular malar mound occurred with greater
to produce deepening of the violaceous color frequency in those older than 50 years, and linear
may serve as useful diagnostic tool to confirm the regression analysis showed that a recommendation
vascular cause of the pigmentation.69 Moreover, for surgery was based on the extent of fat prolapse,
in their review on this subject, Roh and Chung69 skin elasticity, and midface descent.
state that the successful use of autologous fat Surgical intervention, laser resurfacing, soft tissue
transplantation to reduce the appearance of hyper- fillers,78 neurotoxins, and energy-based skin tight-
vascularity supports the idea that it is the vascula- ening may be used in varying combinations to
ture found within the muscle instead of the address this complaint. Nonetheless, despite the
combination of thin skin and subcutaneous vascu- evidence in support of an anatomic basis for
larity that plays a greater role in the appearance of under-eye puffiness and bags, patients seek recom-
these violaceous infraorbital dark circles. mendations for cosmeceuticals that can diminish
In addition to autologous fat transplantation, their appearance. Most products used for this indi-
various modalities, including laser and other cation contain ingredients to reduce fluid retention,
energy-based devices as well as soft tissue fillers, strengthen the vasculature, and improve skin laxity.
have been tried with varying success. In keeping
with the theme of adjunctive skin care of the SKIN CARE INGREDIENTS FOR DARK CIRCLES
eyelids, topical agents that exert effects on the AND PUFFY EYES
vasculature will be discussed, although, as is the
case with many cosmeceuticals, controlled clinical An Internet search for products for “dark circles and
studies to support their use are lacking. puffy eyes” yielded 621,000 results, a testament to
the vast array of skin care products devoted to the
Shadowing treatment of these common problems. The lack of
Shadowing due to intrinsic and extrinsic aging of controlled trials precludes an evidence-based
the skin that leads to skin laxity,75 in combination approach and much of the available information
with age-related changes in the soft tissue and regarding the efficacy of these skin care products
skeleton, is another common cause of dark circles. is anecdotal and largely dependent on testimonials
The appearance of a “tear trough” depression and marketing campaigns. In preparing this article,
secondary to loss of subcutaneous fat and several ingredients were noted to be incorporated
 Adjunctive Skin Care 231

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

RevaléSkin Replenishing Eye Therapy

Key ingredients: 1% CoffeBerry extract
Indications: photoaging, puffiness

Lumière Riche Bio-restorative Eye Balm (NEOCUTIS, Inc. San Francisco, CA)
Key ingredients: PSPÒ (purified skin proteins- a mixture of human growth factors, cytokines, and
interleukins), caffeine, hyaluronic acid
Indications: photoaging, dark circles, puffiness

ELASTIdermÔ EYE Complete ComplexÔ Serum (Obagi Medical Products, Long Beach, CA)
Key ingredients: caffeine, malonic acid, arginine
Indications: photoaging, puffiness

ReplenixÒ 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 MDÔ Ultimate Lift + Correcting Eye Cream (Valeant Pharmaceuticals, Bridgewater, NJ)
Key ingredients: kinetin (0.1%)-Zeatin (0.1%) Complex; Eye RegenerÒ (a registered trademark of Silab,
Brive Cedex, France)- derived from white lupine and alfalfa seed, acts to enhance lymphatic drainage;
IntensylÒ (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)
232 Bucay & Day

Table 1
(continued)

MEG 21 EYE TREATMENT (Dynamis Skin Science, Inc., Jenkintown, PA)

Key ingredients: SupplamineÒ, 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

into many of the product lines researched for this L-ascorbic acid, THD, ascorbyl palmitate, ascorb-
topic. This list is by no means exhaustive and, for yl glucosamine, sodium ascorbyl phosphate, as-
the sake of simplicity, ingredients are listed under corbyl glucoside, and ascorbyl tetraisopalmitate.
the heading that best describes the underlying  Soy: antioxidant and antiinflammatory; inacti-
cause/targeted problem: vates keratinocyte cell receptors that mediate
transfer of melanosomes from melanocytes to
Puffiness keratinocytes
 Epilobium angustifolium extract (willow herb):  Niacinamide (vitamin B3): antioxidant and antiin-
antimicrobial, anti-irritant and antiinflammatory flammatory; increases levels of free fatty acids
properties and ceramides in the skin and decreases trans-
 Dipeptide-2: also known as Eyeliss; improves epidermal water loss; improves hyperpigmenta-
lymphatic circulation and drainage; inhibits tion by decreasing melanosome transfer from
angiotensin-converting enzyme (ACE); the melanocyte to the keratinocyte.
strengthens capillaries  Retinol (retinaldehyde, retinyl palmitate):
 Hesperidin methyl chalcone: improves vascular increases cell turnover; inhibits tyrosinase to
integrity by strengthening capillaries; decreases decrease melanin production
capillary permeability  Azelaic acid: tyrosinase inhibitor
 Caffeine: antioxidant, anti-irritant, purported to  Lignin peroxidase: enzyme derived from the tree
decrease fat when applied topically fungus Phanerochaete chrysosporium that breaks
 Green tea and coffeeberry polyphenols: antioxi- down lignin (found in tree bark); also breaks down
dant, antiinflammatory, anti-irritant melanin, which is structurally similar to lignin
 Palmitoyl tetrapeptide-7: peptide that improves Vascular Pigmentation
skin elasticity, firmness, and tone by increasing
collagen, hyaluronic acid, and fibronectin  Chrysin: involved in the clearance of bilirubin,
 Palmitoyl oligopeptide: also known as Dermaxyl; a breakdown product of hemoglobin
boosts cell communication and dermal repair  N-hydroxysuccinimide: increases the elimination
mechanisms of hemoglobin breakdown products and
 Palmitoyl tripeptide-5: also known as Syn-Coll; increases clearance of iron by rendering it soluble
increases collagen 1 production via TGF-b;  Vitamin K: antiinflammatory effects as well as
reportedly 60% more effective than palmitoyl effects on circulation and/or clotting
pentapeptide  Chrysin, N-hydroxysuccinimide, palmitoyl
tetrapeptide-3, palmitoyl oligopeptide: this
combination is known as Haloxyl. Please refer
Hyperpigmentation (Melanin) to Table 1 for a list of physician dispensed eye
 Arbutin: from bearberry; precursor of creams that contain some of the key ingredients
hydroquinone listed below.
 Hydroquinone: decreases melanin synthesis by
blocking tyrosinase EYELASHES AND EYEBROWS
 Kojic acid: byproduct of fermentation process in
malting rice used in sake production; decreases A thorough discussion regarding adjunctive skin
melanin production; unstable compound so care of the periorbital region should include
a more stable kojic dipalmitate is often used in a mention of eyelash and eyebrow enhancing
skin care products but may not be as effective agents. Since its approval by the FDA in December
 Vitamin C: antioxidant and antiinflammatory; 2008, the only FDA-approved agent for the
reduces hyperpigmentation and increases enhancement of eyelash growth is bimatoprost
collagen production; forms of vitamin C include ophthalmic solution 0.03%, although countless
ascorbic acid, magnesium ascorbyl phosphate, over-the-counter products that claim to enhance
 Adjunctive Skin Care 233

eyelashes and eyebrows can be found in a variety such as chemical peels or laser resurfacing, may
or retail outlets ranging from drugstores to be more adequate. Treatment of dynamic rhytids
high-end department stores. Several skin care is better addressed by neuromodulators. In many
companies also manufacture lash-enhancing and cases, a combination approach is the most appro-
brow-enhancing products for office dispensing. priate approach to treating the signs of photodam-
The mechanism of action by which bimatoprost age. In this setting, adjunctive skin care is used for
improves lash growth is not completely under- maintenance.
stood but is thought to involve an increase in the Without controlled studies, the use of topical
percentage of eyelash follicles in anagen, which antioxidants, growth factors, peptides, and DNA
may account for increased eyelash length. Bima- repair enzymes is based more on their potential
toprost also exerts a stimulatory effect on melano- benefits and not proof. Monitoring of patients
genesis, which may result in darker lashes. and the reporting of any complications, such as
Increased lash thickness and fullness may be skin cancer, may be indicated, even for cosme-
due to an increase in size of the hair bulb and ceuticals. Realistically, this may be difficult, given
dermal papilla.79 Its safety, efficacy, and tolera- that many of these products are recommended
bility are well documented.80,81 and dispensed by nonmedical personnel, such
The successful use of bimatoprost for eyelash as an aesthetician, in the setting of the physician’s
enhancement has led to its off-label use to treat office, a medical spa, or a retail outlet.
eyebrows and, in the experience of the authors, Products targeting infraorbital dark circles and
is something often initiated by the patient with puffiness may be effective in mild cases. An under-
successful results. Although not FDA-approved standing of the underlying causative factors is
for this purpose, a recent publication seems to needed to guide treatment. In some instances,
support the use of bimatoprost ophthalmic solu- fillers or energy-based devices using radiofre-
tion 0.03% for eyebrow growth.82 quency or high-density focused ultrasound may
be a better option; in others, surgery may be the
Side Effects of Lash Growth Products best treatment.
Even in the setting of the initial visit, the authors do
Side effects of lash-enhancing products include
not hesitate to refer a patient for surgery when indi-
itchy eyes, redness of the eyes, temporary hyper-
cated. Patients appreciate candor and honesty and
pigmentation of eyelid skin, and hair growth in
will be happy to return for maintenance, whether it is
other areas that come into contact with the
skin care, botulinum toxin, fillers, chemical peels,
product. Please refer to the Latisse product insert
laser resurfacing, or energy-based therapies.
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- SUMMARY
tion used intraocularly for glaucoma.
An aging population and the availability and
acceptance of surgical procedures to treat the
Patient Expectations Compared with Results
signs of aging of the periorbital area have been
of Using Adjunctive Skin Care and Lash
accompanied by the development of minimally
Growth Products
invasive aesthetic procedures for rejuvenation of
In the authors’ view, patients want and may even this region. A deeper understanding of the contrib-
expect surgical results from a topically applied utory anatomic and physiologic factors underlying
product. It is important to set realistic expectations common cosmetic concerns, such as fine lines
regarding the role of adjunctive skin care and lash and wrinkles, under-eye dark circles, and under-
growth products. With the exception of topical eye puffiness, has allowed us to tailor treatments
prescription retinoids and a prescription lash to the individual’s needs.
growth product, there is a paucity of controlled A parallel explosion in the skin care industry,
clinical studies that prove the benefits and efficacy particularly in the arena of cosmeceuticals, has
of topical cosmeceutical preparations, which is added to the palette of resources available to
not to say that there is not scientific evidence address these common cosmetic concerns. UV
underlying the rationale for their use. radiation is the number one cause of photodam-
Signs of early photodamage, such as fine lines age, making sun protection the pillar of any
and shallow wrinkles, often respond to topically adjunctive skin care regimen. That said, a skin
applied products, provided that the patient is care regimen consisting of topically applied reti-
compliant regarding sun protection and uses the noids, antioxidants, collagen boosters, and DNA
product consistently. In moderate-to-severe repair enzymes may be useful as a stand-alone
cases of photodamage, resurfacing procedures, treatment or as maintenance therapy, whether
234 Bucay & Day

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mind the patient’s medical history. In the context tion of human macrophage metalloelastase in human
of human growth factors, there is still much to be skin in vivo. J Invest Dermatol 2002;119(2):507–12.
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“hot” compounds found in some skin care products Toiletries 1993;108:99.
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