Periorbital Hyper pigmentation
Introduction
Periorbital hyper pigmentation (POH), also known as periocular hyper
pigmentation, periorbital melanosis, dark circles, infraorbital darkening,
infraorbital discoloration, or idiopathic cutaneous hyperchromia of the orbital
region, is a common condition encountered in dermatology practice. It is
an ill-defined entity that presents as bilateral round or semicircular
homogenous brown or dark brown pigmented macules in the periocular
region. It can affect an individual’s emotional well-being and influence
quality of life.
It is more prevalent in women than men and the majority of the
affected women are housewives.
Classification
Classification is on the basis of clinical pattern of pigmentation
and vasculature. Periorbital hyper pigmentation is classified into
pigmented (brown color), vascular (blue/pink/purple color), structural (skin
color), and mixed type based on the clinical appearance assessed by the
physician. The mixed type of dark eye circle included the following four
subtypes: as pigmented-vascular (PV), pigmented-structural (PS),
vascular-structural (VS), and a combination of the three.
Pigmented type (P) appears as infraorbital brown hue. Vascular (V)
type appears as infraorbital blue, pink, or purple hue with or without
periorbital puffiness. Structural type (S) appears as structural shadows formed
by facial anatomic surface contours. It can be associated with infraorbital
palpebral bags, blepharoptosis, and loss of fat with bony prominence. Mixed
type (M) combines two or three of the above appearances. This classification
can help in introducing the therapeutic modalities on the basis of POH type, as
different types of POH respond to different types of treatment.
Clinical Features
Clinically, POH is characterized by light- to dark-colored,
brownish-black pigmentation surrounding the eyelids. It gives a tired look to
the patient. Diagnosis is mainly based on clinical examination. It is important
to differentiate the dark eyelid skin with shadowing due to tear trough. Manual
stretching of the lower eyelid skin can help to differentiate between true
pigmentation and shadowing effect. Although the former retains its appearance
with stretching, the latter improves or resolves entirely. An increase in
violaceous discoloration on manual stretching of the lower eyelids is due to
thin eyelid skin or hypervascularity of lower eyelid.
Wood’s lamp examination can be done to differentiate between the
epidermal and dermal pigmentation. The variations in epidermal pigmentation
become more apparent under Wood’s light. For dermal pigmentation, this contrast
is less pronounced. Ultrasonographic evaluation can help to differentiate the
vascular cause from the periorbital puffiness.
Histopathology
Histological characteristics of periorbital hyper pigmentation
suggest that it can be both epidermal and dermal in nature. Biopsy specimen
must be stained with routine hematoxylin and eosin. Special stains can also be
used. Fontana-Masson silver stain can be used to stain melanin. Hemosiderin
deposits seen in few cases (resulting from extravasation and superficial
location of vasculature) can be stained with Perl’s potassium ferrcyanide.
Etiology
Various exogenous and endogenous factors are possibly implicated
in its pathogenesis. The causative factors include genetic or heredity,
excessive pigmentation, post inflammatory hyper pigmentation secondary to
atopic and allergic contact dermatitis, periorbital edema, excessive
vascularity, and shadowing due to skin laxity and tear trough associated with
aging.
Genetics
Periorbital hyper pigmentation is considered to have a genetic
basis with a positive family history. Many of them recognized the pigmentation
early in childhood and stated that pigmentation increased with age. They were
also aware that stress made pigmentary changes more intense, while rest and
good health seems to produce lessening of color.
Periorbital pigmentation due to dermal melanocytosis
Dermal melanocytosis is characterized by the presence of
melanocytes in the dermis. Clinically, these lesions are recognizable by their
distinctive grey or blue-grey appearance. Dermal melanocytosis causing periocular
hyper perpigmentation can be due to congenital or acquired causes. Dermal
melanocytosis can be placed into the pigmentary class of Huang et al’s
classification.
Nevus of Ota, also known as oculodermal melanocytosis or nevus
fusco caeruleus ophthalmo maxillaris, is a type of congenital dermal
melanocytosis that involves the areas innervated by the first and second
divisions of the trigeminal nerve. It appears as speckled or mottled brown-grey
to blue-black patches that may involve the skin, conjunctiva, sclera, tympanic
membrane, or oral and nasal mucosa of the affected dermatomes. If it is located
infraorbitally, it can be a cause of periorbital hyper pigmentation.
Nevus of Hori was first described in 1984 by Hori et al and is
defined as acquired, bilateral nevus of Ota-like macules. Clinically, it
presents with blue-brown to slate-grey mottled hyper pigmentation with a
predilection for the malar region, which may extend to involve the periocular
area causing dark circles. A distinct lack of ocular or mucosal involvement
differentiates the nevus of Hori from other forms of dermal melanocytosis.
Reports have linked sun exposure, hormonal changes in pregnancy, and chronic
atopic dermatitis to occurrence of nevi of Hori.
Post inflammatory hyper pigmentation
Excessive pigmentation can also be due to post inflammatory hyper
pigmentation secondary to atopic and allergic contact dermatitis and other
dermatological conditions (e.g., lichen planus pigmentosus) and can be drug
induced, such as in the case of fixed drug eruptions. Periorbital hyper
pigmentation can be caused by rubbing and scratching of skin around the eyes
and by accumulation of fluid due to allergy as in atopic dermatitis and
allergic contact dermatitis.
Superficial location of vasculature
Superficial location of vasculature and thin skin overlying the
orbicularis oculi muscle is another common cause of periorbital hyper
pigmentation. This condition usually involves the entire lower eyelids
with a violaceous appearance due to prominent blood vessels covered by a thin
layer of skin, more in the inner aspect of the eyelid, and is usually
accentuated during menstruation. When the lower eyelid is manually stretched,
the area of darkness spreads out without blanching or significant lightening
and results in deepening of violaceous color, which could be used as a
diagnostic test to confirm the vascularity.
Tear trough depression
Tear troughs represent an anatomical location that becomes depressed with age, centered over the inferio-medial orbital rim. It is an age-related change. It occurs mainly because of loss of subcutaneous fat and thinning of overlying skin of the orbital rim ligaments, combined with cheek descent, conferring hollowness to the orbital rim area. A combination of the hollowness and the overlying pseudoherniation of the infraorbital fat accentuate the shadowing in the tear trough causing dark circles, depending on the lighting condition.
Periorbital edema
The eyelid region has a spongy property, which can lead to fluid
accumulation due to systemic and local causes. Diagnostic features that suggest
edema includes worsening in morning or after eating salty meals. The history of
variability in intensity and extension is important to determine the influence
of edema on periorbital hyper pigmentation. When compared with normal
orbital fat, edema is still present in downward gaze and does not change much
in upward gaze.
Extension of pigmentary demarcation lines of face
Pigmentary demarcation lines (PDL) are borders of abrupt
transition between hyper pigmented skin and lighter areas. According to the
site, they have been labeled A to H lines. F and G types are present over the
lateral side of orbit and present as V-shaped and W-shaped patches,
respectively.
Ocular hypotensive drugs
Prostaglandin analogues, such as latanoprost and bimatoprost, which are used as ocular hypotensive eye drops in patients with glaucoma, can also cause periorbital hyper pigmentation. Patients develop periocular hyper pigmentation most frequently between 3 to 6 months of initiating bimatoprost therapy. Complete reversal of pigmentation occurs after discontinuation of bimatoprost. It was reported that the increased melanogenesis in dermal melanocytes and increased transfer of melanin granules to basal epidermis is the likely mechanism of bimatoprost-induced hyper pigmentation.
Environmental Causes
Ultraviolet radiation
aggravates POH, and some lifestyle factors may contribute to developing
POH, including lack of sleep, stress, alcohol overuse, and smoking, although
not clinically substantiated.
Treatment
There are a number of treatment options available for POH. Among
the available treatment options for POH include topical depigmenting agents,
such as hydroquinone, kojic acid, azelaic acid, topical retinoic acid, and
physical therapies, including chemical peels, surgical corrections, and laser
therapy. The aim of treatment should be to identify and treat the primary cause
of hyper pigmentation as well as its contributing factors. Also different
modalities are used according to cause of POH.
Topical agents
Topical phenolic or nonphenolic bleaching agents are used in the
treatment of hyper pigmentation, particularly hydroquinone and tretinoin. The
mechanism of action of most bleaching agents is inhibition of tyrosinase
enzyme, which inhibits the conversion of dopa to melanin, hence leading to a
reduction of the melanin content of the epidermis.
Hydroquinone
Also known as 1, 4dihydrobenzene, hydroquinone is the most
prescribed bleaching agent worldwide. It is used in strengths of 2 to 6%. The
effect of treatment generally becomes evident after 5 to 7 months of therapy;
hence the treatment should be given for at least three months.
Frequently observed acute side effects include mild skin
irritation, itching, post inflammatory hyper pigmentation, and transient
hypochromia. Long-term use can lead to exogenous ochronosis, leukomelanoderma
en confetti, nail discoloration, and colloid millium.
Hydroquinone has also been used safely in the periocular
area.
Triple combinations
The United States Food and Drug Administration (FDA) has approved
a modified combination of the Kligman’s formula, containing 4% hydroquinone,
0.05% tretinoin, and 0.01% fluocinolone acetonide for use in melasma and
various other pigmentary disorders, but its long-term use in the
periorbital area is a concern since it contains a topical steroid.
Kojic acid
Kojic acid is a naturally occurring fungal derivative produced
by Aspergillus species and Penicillium species.
It acts by inhibiting tyrosinase, and is used in a concentration ranging from 1
to 4%.
In a study conducted by Lim et al, it was found that the
addition of kojic acid to a gel containing 10% glycolic acid and 2%
hydroquinone further improves pigmentation in melasma. Although there are no
studies, kojic acid has been tried anecdotally in the treatment of periorbital hyper
pigmentation and has been found to be effective. Side effects of kojic acid
include erythema and contact dermatitis.
Azelaic acid (AzA)
Azelaic acid (1, 7- heptanes dicarboxylic acid) was initially
developed as a topical antiacne agent, but because of its effect on tyrosinase,
it has also been used in the treatment of hyperpigmentary disorders such as
melasma. Its mechanism of action includes the inhibition of DNA synthesis and
mitochondrial enzymes, thereby inducing direct cytotoxic effects on the
melanocyte.
In vitro studies show that
AzA interferes with DNA synthesis and mitochondrial enzymes in abnormal
melanocytes and fibroblasts, thus neither leukoderma nor exogenous
ochronosis are associated with its use. It can be used safely for prolonged
periods of time. Since it was found to be effective for facial post inflammatory
hyper pigmentation, it is a potentially promising agent for periocular hyper
pigmentation due to post inflammatory hyper pigmentation.
Arbutin
Arbutin is an extract of leaves of the bearberry shrub and the
cranberry, pear, or blueberry plants. It inhibits tyrosinase activity, but also
inhibits melanosome maturation. Its effects are dose-dependent, but high
concentrations of arbutin can cause hyper pigmentation. It is available in a
concentration of 3%. Arbutin can also be used in other facial hyper
pigmentation including POH.
Topical vitamin C
Vitamin C, an antioxidant, has also been used for the treatment of
hyper pigmentation. Because ascorbic acid is unstable in many topical
preparations, esterified derivatives, such as L-ascorbic acid 6-palmitate and
magnesium ascorbyl phosphate are used in compounds.
L-ascorbic acid is the predominant cutaneous antioxidant. It
scavenges the free oxygen radicals in the aqueous compartment which trigger
melanogenesis. Vitamin C promotes collagen production and conceals color of
blood stasis, which could improve appearance of dark circles under the lower
eye lid.
Ohshima et al showed that vitamin C and its derivatives, such
as magnesium ascorbyl phosphate and ascorbic acid glucoside, inhibit
melanogenesis in human melanocytes. They used two types of 10% vitamin C
lotion, sodium ascorbate and ascorbic acid glucoside for six months in a
split-faced manner for dark circles. Melanin index, erythema index, thickness,
and echogenecity of the dermis of the bilateral eyelid was measured and it was
found that there was lightening of pigmentation owing to an increase in dermal
thickness due to concealment of dark discoloration from congested blood.
However, they did not find any significant difference in melanin index.
Sunscreens
Hyper pigmentation can be improved with sunscreen alone as
reported by Guevara and Pandya in a study conducted in patients with melasma. Patients
should be cautious while using chemical sunscreen in the delicate eye area.
Similarly, broad spectrum sunscreen and ultraviolet (UV) coated sunglasses are
considered to be beneficial in POH.
Chemical peels
Chemical peels may be used alone or in combination with treatments
such as topical bleaching agents. Glycolic acid is the most widely used alpha
hydroxy acid for chemical peeling. Glycolic acid 20% can also be used for
periocular hyper pigmentation. Lactic acid 15% has been used in periorbital hyper
pigmentation in combination with trichloroacetic acid (TCA) 3.75% by Vavouli et
al and it was found that almost all the patients showed significant
esthetic improvement. For treatment of POH in medium to darker skin, it is best
to extend the peel to the entire face to avoid post-peel demarcation. For
optimal outcome, pretreatment with a tretinoin and hydroquinone bleaching agent
for 2 to 4 weeks is recommended before undergoing a chemical peel. The most
disturbing side effect of chemical peels can be post inflammatory hyper
pigmentation. This may be minimized with the help of priming agents, such as
hydroquinone and tretinoin.
Lasers
Periorbital hyper pigmentation has been successfully treated with
various noninvasive lasers that target pigment and vascularity. Various lasers
that have been used for treating dark circles are: Q switched ruby laser (694
nm), Q switched alexanderite laser, and Nd:Yag laser (1064nm).
In a study conducted by Watanabe et al, patients with
homogenous bilateral pigmented macules in the periorbital region were selected
for study of dark circles. Five patients with infraorbital dark circles
received 1 to 5 treatments with the Q switched ruby laser (694nm); four
patients showed good response and two patients showed excellent results.
In another study on POH, Momosawa et al combined Q switched
ruby laser with a bleaching agent containing 0.1% tretinoin and 5% hydoquinone.
The bleaching agent was applied for six weeks before the laser treatment. The
purpose of this treatment was to improve epidermal pigmentation by accelerated
discharge of epidermal melanin by tretinion and suppressing new epidermal
melanogenesis by hydroquinone ointment. Fifteen out of 18 patients showed
excellent or good results after 3 to 4 laser treatments with no complications.
Thus, it was concluded that in treating POH, the Q switched ruby laser should
be considered as first-line treatment and it was found effective in both dermal
and epidermal pigmentation. The Nd:Yag laser (1064nm) is also effective in
reducing the pigmentation and vascular component of infraorbital dark circles.
Skin laxity and tear trough deformity are age-related changes that
they can be treated with lasers. Alster and Bellew treated 67 patients
with dermatochalasia and periorbital rhytides using CO2 laser
resurfacing and found significant improvement.
Although ablative laser resurfacing is a well-accepted treatment
modality for improving the appearance of photo-induced rhytides coexisting with
periocular hyper pigmentation, but due to untoward side effects such as
prolonged erythema, pigmentation, and infection, and in some cases scarring,
great interest has been shown toward less invasive methods to treat
photo-induced rhytides effectively. These include the pulsed dye laser, diode
laser, 1064nm Nd:YAG laser, 1320nm Nd:YAG laser, 1540nm erbium glass laser, and
intense pulsed light laser sources.
Autologous fat transplantation
Autologous fat transplantation is used to treat periorbital hyper
pigmentation due to thin and translucent lower eyelid skin overlying the
orbicularis oculi muscle.
Fillers
Hyaluronic acid gel is used as filler for three-dimensional
reshaping of periorbital complex. Patient satisfaction is high, but some
patients with dark circles noted darker pigmentation after hyaluronic acid gel.
Bosniak et al treated 12 patients with POH, tear trough deformity, or
prominent nasojugal groove with the hyaluronic acid push technique. All
patients experienced immediate improvement after the procedure. Excellent tear
trough contour improvement was achieved in all patients and under eye dark
circle improved. Minor post-injection erythema and edema were observed, which
resolved within 72 hours.
Platelet-rich plasma
Recently, platelet-rich plasma has been used in treating dark
circles due to tear trough deformity and wrinkles. A single session with
intradermal injections of 1.5mL platelet-rich plasma was given into the tear
trough area and wrinkles of crow’s feet. Effect was compared three months after
treatment with baseline. The improvement in infraorbital color homogeneity was
statistically significant.
Surgery. Blepharoplasty
Blepharoplasty helps in eliminating dark circles caused by shadows
that are cast by fat deposits or excess skin. Transconjunctival blepharoplasty
is a better approach than transcutaneous blepharoplasty so that no external
visible scar is created. Epstein used transconjunctival blepharoplasty and deep
depth phenol peel simultaneously to treat hyperpigmentaion of skin and
pseudoherniation of orbital fat, which is a contributing cause for infraorbital
dark circles.
Conclusion
Periorbital hyper pigmentation is a commonly encountered
condition. It is less responsive to standard therapies due to its multi factorial
etiology and deposition of melanin in both dermis and epidermis. However, even
a mild-to-moderate improvement in appearance can cause an improvement in the
quality of life of the patient, hence topical therapies and simple physical
therapies such as chemical peels can be used to treat the patients who want to
improve the cosmetic appearance of their face.
