Demodex mites are the most common microscopic ectoparasite found in the human skin. The rate ofDemodex infestation increases with age, being observed in 84% of the population at age 60 and in 100% of those older than 70 years [1]. Apart from its higher density in patients with rosacea [2–5], Demodex mites have also been suggested as a cause of other skin diseases such as pityriasis folliculorum, perioral dermatitis [6], scabies-like eruptions, facial pigmentation, eruptions of the bald scalp, demodicosis gravis, and even basal cell carcinoma [7]. Because the eye is surrounded by such protruding body parts as the nose, the brow, and the cheek, the eyelid is not as accessible as the face to daily cleansing hygiene. Therefore, onceDemodex infestation establishes in the face, it is likely to spread and flourish in the eyelids leading to blepharitis [8–11]. Despite this, the clinical significance of Demodex infestation remains debatable in part because it can be found in asymptomatic subjects. As a result, Demodex blepharitis is often overlooked in differential diagnosis of corneal and external diseases let alone therapeutic options are considered. Herein, we would like to summarize the key literature and our research experience regarding the pathogenic potential ofDemodex mites in causing ocular surface inflammation with a special emphasis on blepharitis.

Two distinct species have been identified in human: Demodex folliculorum and D. brevis (Fig. 1). In the eyelids, D. folliculorum can be found in the lash follicle, whereas D. brevis burrows deep into sebaceous glands and meibomian glands looking for sebum which is thought to be their main food source. It has also been proposed that these mites might feed on follicular and glandular epithelial cells leading to direct damage of the lid margin. The life cycle of the Demodex mite is approximately 14–18 days from the egg to the larval stage followed by 5 days in the adult stage. Females may live an additional 5 days after oviposition [12]. Because of the limited life span of the adult mites, mating plays an important role in perpetuating Demodexinfestation. Furthermore, Demodex’s life span is limited outside the living body, thus, direct contact is required for transmission of mites. Accordingly, it is important to prevent mating of mites and avoid direct transmission as an indispensable treatment strategy.

Recently, we have demonstrated a close correlation between the severity of rosacea and Demodex blepharitis [13••]. Rosacea predisposes patients to blepharitis mainly by creating an environment on the skin that congests all the oil-producing glands necessary for a healthy dermis and epidermis. Other factors may change the environment to encourage mites’ proliferation, such as the skin phototype, sunlight exposure, alcohol intake, smoking, stress, hot beverages, spicy food, and abrupt changes in temperature [14,15]. Because of the anatomic feature of the face, eyelids are not accessible to routine cleansing hygiene providing a favorable environment for Demodex mites to spread and flourish. Infestation of Demodex mites is prone to develop in patients whose local or systemic immune status is compromised by topical or systemic administration of steroids or other immunosuppressive agents or by diseases such as leukemia and HIV [16].

Various treatments have been used to control Demodex mites such as mercury oxide 1% ointment, pilocarpine gel, sulfur ointment, and camphorated oil. Most of them involve spreading an ointment at the base of the eyelashes at night to trap mites as they emerge from their burrow and/or move from one follicle to another. However, using an in-vitro microscopic observation for a period of 150 min, we found that adult D. folliculorum is resistant to a wide range of common antiseptic solutions including 75% alcohol and 10% povidone–iodine, and such antimicrobials as erythromycin and metronidazole but can dose-dependently be killed by tea tree oil (TTO) [29]. Unlike Baby shampoo, lid scrub with TTO not only cleanses cylindrical dandruff from the lash root but also stimulates embedded mites to migrate out to the skin. As a result, daily lid scrub with 50% TTO and lid massage with 5% TTO ointment are effective in eradicating ocular Demodexinfestation in vivo, as evidenced by bringing the Demodex count down to zero in 4 weeks in a majority of patients [19,25,30] (Fig. 4). The two treatments were equally effective in eradicating mites although we presume they may act differently. The 50% TTO has direct killing effect on the mites, whereas the 5% may interrupt their life cycle by preventing mating. Apart from Demodex eradication, TTO treatments resulted in dramatic alleviation of symptoms and marked resolution of inflammation in the lid margin, conjunctiva, and cornea [19]. Because TTO also may exert antibacterial [25,31,32] antifungal [33–37], and anti-inflammatory actions [38,39], we cannot attribute its therapeutic benefit in treating the above eye diseases solely to its effect of killing mites. As the Demodex also serves as the vector of the skin organisms, the comorbidity based on a symbiotic relationship of B. oleronius in Demodex mites also justifies the consideration of a therapeutic strategy directed to killing the symbiotic bacterium via oral antibiotics such as tetracycline.

Demodex mite plays an important role in the occurrence of a series of ocular surface diseases such asDemodex blepharitis, meibomian gland dysfunction, conjunctival inflammation, and corneal lesions. Ocular infestation has a close relationship with the systemic infestation. Further studies are needed for developing easy and sensitive diagnostic methods and more effective and specific treating regimens.