By Sara Hover, RPh, FAARM, PCCA Clinical Compounding Pharmacist

Periorbital hyperpigmentation is a skin disorder that appears in those with darker skin pigmentation. It is also known as idiopathic cutaneous hyperchromia of the orbital region or, commonly, “dark circles.” Clinically, it presents with medium to deep brown hyperpigmentation around the bilateral orbital skin and eyelid, sometimes extending to the upper nose and between the eyebrows. The discoloration may be present on the upper, lower or both eyelids.¹ It can be a significant cosmetic concern for patients, especially when they feel it makes themselves appear sad, tired, stressed or older than they are.² But it also could be a warning sign of more serious medical problems, including disorders of the liver, heart, thyroid or kidneys; hereditary blood disorders; allergic reactions; nutrient deficiency, such as that of vitamin K; Addison’s disease; circulatory conditions resulting in fluid retention; or even sleep disturbance.^2,3

Causes
Periorbital hyperpigmentation is caused by various external and internal factors, which makes it very complex to treat. The factors can include genetics, excessive pigmentation from melanin deposited in the epidermis and dermis, post-inflammatory hyperpigmentation due to contact or atopic dermatitis, periorbital edema, excessive vascularity, reduced thickness of the epidermis, and tear troughs associated with aging.^2,4

Latanoprost Warning
Latanoprost, bimatoprost and other prostaglandin analogs can also cause periorbital hyperpigmentation. These are often used as ocular hypotensive eye drops for patients with glaucoma or lash growth. When bimatoprost drops cause this condition, it usually develops between three and six months after initiating the treatment. The likely mechanism of action is due to an increase in melanogenesis in dermal melanocytes and increased transfer of melanin granules to the basal epidermis. However, the hyperpigmentation typically reverses when the treatment is discontinued.⁴

Testing
Because of the various potential causes of this condition, testing to determine the underlying cause can be helpful in developing a course of treatment. One option is a dermoscopy, which may reveal if the pigmentation is due to melanin or underlying vasculature.² Histopathologic examination is another option. This can help determine if it is epidermal, dermal, or mixed pigmentation with no other significant changes. A Fontana-Masson silver stain is an option for detecting melanin, and a Perls’ potassium ferricyanide stain can detect hemosiderin deposits in the tissue.³ Hemosiderin staining (iron staining) of the tissue is treated differently since it isn’t related to excessive melanin. 

Potential Treatment Options

• Here are some potential options to consider:
• Periorbital hyperpigmentation caused by melanin is typically treated with hydroquinone and similar ingredients along with lasers³
• Hydroquinone is an antagonist of tyrosinase, a copper-containing enzyme that factors heavily in pigmentation. A range of hydroquinone concentrations can be compounded. Using around 2–8% concentration may stabilize the melanocytes and decrease pigmentation locally³
• Kojic acid binds to copper, also blocking the tyrosinase pathway³
• Cases caused by vascularity are often treated by targeting the vessel walls to stabilize them, and the use of ascorbic acid (vitamin C), phytonadione (vitamin K1) and tretinoin may help³
• Ascorbic acid can effectively lighten pigmentation, possibly due to an increase in dermal thickness that reduces dark discoloration from underlying congested blood⁴
• Retinoids are vitamin A derivatives, like tretinoin, that decrease the appearance of hyperpigmentation through multiple pathways. They promote collagen synthesis and reorganization. They also decrease melanin content³
• Mixed-type periorbital hyperpigmentation may respond best to combination therapy³
• Concealers and cosmeceuticals are the least invasive options. Optical diffusers can reduce the appearance of dark circles, but these only cover up the condition³

Something New
Hydroquinone and ascorbic acid are not new to this clinical area, but having a base that can stabilize them is. PCCA’s W06™ Anhydrous Topical Gel is a base that has a water activity below 0.6 (Aw < 0.6). It was created to accommodate challenging active pharmaceutical ingredients like hydroquinone and ascorbic acid while giving longer beyond-use dates by default. As well as being a great base, W06 provides moisture and softens the skin.

Example Formulas
PCCA has several formulas that compounders can consider as options when working with practitioners and their patients. PCCA members with Clinical Services access can view these formulas here, and if they have questions about compounding for patients with periorbital hyperpigmentation, they can contact our Clinical Services department at 800.331.2498.

Sara Hover, RPh, FAARM, has been a compounding pharmacist for over 20 years and joined the PCCA Clinical Services team in June 2013. Before joining the PCCA staff, she was the owner and pharmacist of Creative Compounds in Prosper, Texas, an independent, compounding-only pharmacy that focused on women’s health and nutrition. In addition to her expertise in hormone replacement therapy, Sara possesses a vast knowledge of homeopathics as well as herbal and vitamin supplements. Sara obtained her Bachelor of Science degree from the University of Texas at Austin in 1994. She is a lifetime member of the University of Texas College of Pharmacy Alumni Association.

A version of this article originally appeared in PCCA’s members-only magazine, the Apothagram.

References
1.    Vashi, N. A., Wirya, S. A., Inyang, M., & Kundu, R. V. (2017). Facial hyperpigmentation in skin of color: Special considerations and treatment. American Journal of Clinical Dermatology, 18(2), 215–230. https://doi.org/10.1007/s40257-016-0239-8
2.    Jage, M., & Mahajan, S. (2018). Clinical and dermoscopic evaluation of periorbital hyperpigmentation. Indian Journal of Dermatopathology and Diagnostic Dermatology, 5(1), 42–47. https://doi.org/10.4103/ijdpdd.ijdpdd_2_18
3.    Daroach, M., & Kumaran, M. S. (2018). Periorbital hyperpigmentation − An overview of the enigmatous condition. Pigment International, 5(1), 1–3.
4.    Sarkar, R., Ranjan, R., Garg, S., Garg, V. K., Sonthalia, S., & Bansal, S. (2016). Periorbital hyperpigmentation: A comprehensive review. The Journal of Clinical and Aesthetic Dermatology, 9(1), 49–55.

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The references cited did not necessarily evaluate PCCA products or formulas included in these statements. The information contained herein is not intended to replace or substitute for conventional medical care, or encourage its abandonment.