Demodex Blepharitis

This overlooked cause of blepharitis represents a therapeutic challenge.

By Jingbo Liu, MD, PHD; Hosam Sheha, MD, PHD; Yao FU, MD, PHD; and Scheffer C. G. Tseng, MD, PHD

The Demodex mite (class Arachnid and order Acarina) is an elongated ectoparasite that has an obvious head-neck segment with four pairs of legs and a body-tail segment. Two distinct species have been found on human skin: Demodex folliculorum and Demodex brevis (Figure 1). The adult D. folliculorum is 0.35 to 0.4 mm long with four pairs of well-developed legs and a stumpy body. It typically clusters at the root of eyelashes, leading to anterior blepharitis. D. brevis is 0.15 to 0.2 mm long and has an evenly distributed head-to-body ratio. It usually burrows deep into the sebaceous and meibomian glands and causes posterior blepharitis.1,2

The clinical significance of Demodex infestation remains debatable, in part because it can be found in asymptomatic individuals. As a result, ocular inflammation caused by Demodex is often overlooked in differential diagnosis and poses a therapeutic challenge due to the failure of conventional treatments.

PATHOGENESIS
Demodex mites, especially folliculorum, consume epithelial cells at the hair follicle. The resulting follicular distention, epithelial hyperplasia, and reactive hyperkeratinization may contribute to the formation of loose or misdirected lashes, trichiasis, and madarosis.3,4 D. brevis can mechanically block the orifices of the meibomian glands, which prevents lipid secretion over the tear film and gives rise to tear lipid deficiency.5 Both species have a chitinous exoskeleton that may act as a foreign body and cause a granulomatous reaction.

Demodex mites can carry bacteria that will contribute to ocular surface inflammation. Bacteria on the surface of the mites’ skin have been shown to be transported by the parasites from follicle to follicle. Superantigens produced by bacteria, either on the surface of the mites’ skin or inside their bodies, can be recognized by host immune cells, thus leading to inflammation of the eyelids and surrounding skin.6 For example, the protein Bacillus oleroniusDemodex mites, can stimulate the proliferation of peripheral blood mononuclear cells in patients with rosacea.7 Even the waste and protein released by dying mites may trigger a cascade of host inflammatory responses.4

CLINICAL FEATURES
Symptoms
Patients with ocular Demodex infestation often complain of itching, burning, redness, foreign body sensation, scaling at the root of the lashes, dry eyes, and blurry vision.

Signs
Demodex blepharitis can be classified anatomically as anterior and posterior blepharitis. The anterior form with cylindrical dandruff is pathognomonic for ocular Demodex infestation.3 The scales usually form clear cuffs collaring the lash’s root (Figure 2A) and can be easily distinguished from the greasy scales not connected with the root of the lash (Figure 2B). Long-standing cases of Demodex infestation can cause disorders of the eyelashes such as trichiasis and madarosis.

Posterior blepharitis with meibomian gland dysfunction due to blocked orifices of the meibomian gland (Figure 2C) may lead to dry eye symptoms. Inflammation of the lid margin with variable hyperemia, telangiectasia, thickening, and keratinization can also occur (Figure 2D).8 Granulomatous responses in the meibomian glands may lead to hordeolum or chalazion (Figure 2E). The inflammation may extend to the conjunctiva (Figure 2E) as well as the cornea, leading to superficial corneal vascularization, marginal corneal infiltration, a phlyctenule-like lesion, superficial corneal opacity, and/or a nodular corneal scar (Figure 2F).

DIAGNOSIS
At the slit lamp, the clinician epilates two lashes from each eyelid after wiggling the lashes to loosen the cylindrical dandruff and increase the likelihood of detecting Demodex.3,9After mounting the lashes on a glass slide, he or she applies a cover slip and adds a 0.25% fluorescein drop at its edge for better visibility during an examination under a light microscope (Figure 3).

TREATMENT
Although the life span of Demodex mites is limited (14- 18 days),10 mating plays an important role in perpetuating infestation, and reinfestation is common. Accordingly, the aim of treatment should be to eradicate the mites, prevent their mating, and avoid reinfestation. Various approaches have been tried, including mercury oxide ointment, pilocarpine gel, sulfur ointment, and camphorated oil. The idea is to spread an ointment at the base of the eyelashes at night to trap the mites as they move from one follicle to another.

Recently, we found that adult D. folliculorum can be killed dose-dependently by tea tree oil.11 Lid scrubs containing 50% tea tree oil may also lure the mites out of the lash follicles, while the 5% tea tree oil ointment prevents mating and reinfestation from the skin around the eye. We therefore recommend the use of a daily lid scrub with 50% tea tree oil and lid massage with 5% tea tree oil ointment to eradicate ocular Demodex infestation.5,12

CONCLUSION
The Demodex mite plays an important role in the occurrence of Demodex blepharitis that is easily overlooked by eye care professionals. Because it is resistant to most conventional medications, ocular inflammation caused by Demodex infestation is difficult to eradicate. Further studies are needed to develop easy, sensitive diagnostic methods and more effective and specific treating regimens.

A part of the studies described in this article is supported by research grant 1R43 EY019586-01 from the National Institutes of Health, National Eye Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Yao Fu, MD, PhD, is a research fellow at the Ocular Surface Center in Miami. Dr. Fu may be reached at (305) 274-1299, ext. 219; fuyaofy@sina.com.

Jingbo Liu, MD, PhD, is a research fellow at the Ocular Surface Center in Miami. Dr. Liu may be reached at (305) 274-1299, ext. 219; ljingbo@ocularsurface.com.

Hosam Sheha, MD, PhD, is a consultant of ophthalmology at the Ocular Surface Center in Miami. Dr. Sheha may be reached at (305) 710-4709; hsheha2010@gmail.com.

Scheffer C. G. Tseng, MD, PhD, is the medical director of the Ocular Surface Center in Miami and research director of the Ocular Surface Foundation. He has filed two patents for the use of tea tree oil and its ingredients for treating demodicosis. Dr. Tseng may be reached at (305) 274-1299; stseng@ocularsurface.com.