OCULAR DEMODICOSIS

Signs and Symptoms

Demodicosis refers to an infestation by mites of the genus Demodex. In humans, these mites selectively inhabit the skin of the face and head and have been associated with rosacea, steroid-induced dermatitis and seborrheic dermatitis, among other conditions.1-4 When Demodex infest the eyelids and lashes, the condition is referred to as ocular demodicosis or Demodex blepharitis.

The typical patient with ocular demodicosis is over 50 years of age, with increasing prevalence in the elderly population.5-7 There is no known racial or gender predilection.6 Clinical symptoms of blepharitis—itching, burning, sandy or gritty feeling, heaviness of the lids or complaints of chronic redness—are often present in these patients, although a recent study indicates that nearly half of those individuals who harbor Demodex remain asymptomatic.6 The classic sign associated with ocular demodicosis is the presence of collarettes, or scales that form clear casts around the lash root, a finding first recognized by Coston in 1967.8 In 2005, Gao and associates coined the phrase cylindrical dandruff (CD), which is more descriptive of the eyelash sheathing encountered with Demodex infestation.7 The study showed that lashes demonstrating diffuse or sporadic CD had a significantly higher incidence of Demodex organisms than those without CD.7 Additional, nonspecific signs of ocular demodicosis include red and swollen lid margins, trichiasis, eyelash disorganization, madarosis, meibomian gland dysfunction (MGD), blepharoconjunctivitis and blepharokeratitis.9,10 Recent studies also suggest a potential association between Demodex and pterygia and chalazia.11,12

Pathophysiology

Much controversy surrounds the role of Demodex in ocular inflammation. The organism is considered by many to be nothing more than a commensal saprophyte, inhabiting the skin of the host and feeding on accumulated oil secretions and dead epithelial cells.13,14 Others, however, view the mites as parasitic—by definition, thriving in or on the host organism, offering no benefit and potentially causing harm. Judging by the recent literature, the latter view is currently more popular.

Two species of mites are known to inhabit the eyelids and eyelashes of the human host: Demodex folliculorum and the smaller, less prevalent Demodex brevis.5-7,9,10,15 D. folliculorum tends to cluster superficially around the lash root, while D. brevis burrows into the deeper pilosebaceous glands and meibomian glands.11,16,17 As D. folliculorum feed along the base of the lashes, follicular distention occurs, contributing to the formation of loose or misdirected lashes.10 Cylindrical dandruff appears to result from epithelial hyperplasia and reactive hyperkeratinization around the base of the lashes, possibly due to microabrasions from the mite’s sharp claws and cutting mouth-parts (gnathostoma).7,10 D. brevis, in contradistinction, is believed to impact the meibomian glands either by mechanical blockage of the duct, a granulomatous reaction to the mites as a foreign body or as a vector for other microbes that incite the host’s innate immune response.10,11,18 The end result is MGD with associated lipid tear deficiency.19

Of course, not all individuals manifesting Demodex display these pathological changes. Studies have shown that infestation by Demodex induces an upregulation of tear cytokines, particularly interleukin-17, a potent mediator of inflammation.20,21 Whether the symptomology and clinical manifestations associated with demodicosis are related to a critical number of organisms (with a pathological tipping point), concurrent pathogenic bacteria, age, environment or some other factor is yet to be determined.

Management

Because the eye is set back into the orbit, it does not lend itself to routine washing as readily as the rest of the structures of the face; this may in part explain why Demodex seem to flourish in this environment. Simple cleansing of the eyelids with baby shampoo or other surfactant cleaners has been advocated by some as a form of therapy, but studies have shown this to be ineffective as a standalone treatment modality.7,19,22 Salagen (pilocarpine gel 4%, Eisai Pharmaceuticals) applied to the eyelids once or twice daily has also been recommended as a deterrent to mite infestation. This agent is theorized to interfere with the mites’ respiration and motility via toxic muscarinic action.23 However, studies have shown this intervention to be only partially effective, and the parasympathomimetic effects of pilocarpine on pupil size and accommodation must be weighed heavily against the clinical benefit.22-24

Tea tree oil (TTO), naturally distilled from the leaves of the Melaleuca alternifolia plant, appears to be the most widely accepted and most well-substantiated treatment for ocular demodicosis. Numerous derivatives of this essential oil have been advocated for application to the lid margins and lashes, including a 50% TTO in-office therapy, a 10% TTO home therapy, a 5% TTO ointment, a commercially available TTO shampoo and Cliradex (terpinen-4-ol, Bio-Tissue).19,24-27 Cliradex is typically prescribed once or twice daily for three to six weeks. Sensitivity to these solutions tends to be dose and duration dependent, and while complete eradication of Demodex mites may be unattainable for all patients, subjective improvement is the rule rather than the exception. TTO can cause intense discomfort when applied to the delicate skin of the eyelids at full strength and can result in significant ocular toxicity if appropriate care is not taken. Diluting the solution with other natural oils (e.g., coconut oil, walnut oil or macadamia nut oil) is an intermediate step that can improve tolerability. In clinical studies, successful in vivo eradication of mites was seen in 73% to 78% of patients, while symptoms diminished dramatically in 82% of subjects after four weeks of therapy.19,24

While there are currently no studies to support the practice in terms of Demodex management, we have achieved great success with microblepharoexfoliation (MBE) using the BlephEx device (BlephEx). MBE provides ideal induction therapy for demodicosis by rapidly stripping away accumulated sebum, devitalized epithelial tissue, bacterial biofilm, cylindrical dandruff and even the more superficial mites themselves. In our experience, the combined use of MBE with ongoing hygiene efforts and specific, miticidal treatment modalities allows patients to achieve symptomatic relief much more quickly.

For more recalcitrant cases of demodicosis, or in those patients where compliance with topical therapy is unattainable, Stromectol (oral ivermectin, Merck) may provide some clinical benefit. Stromectol is an antihelminthic agent typically prescribed for the treatment of parasitic disorders such as strongyloidiasis or onchocerciasis. In terms of Demodex therapy, two 200mcg/kg doses given seven days apart represents the current standard.28,29 As an example, an adult weighing 165 pounds would be prescribed five 3mg tablets to be taken in bolus form at the time of diagnosis, and an identical dose to be taken one week later. The most common side effects noted include nausea, diarrhea, dizziness and pruritus.30

Because Demodex inhabit various regions of the face and scalp, patients must remain vigilant even after a treatment for ocular demodicosis has been concluded. The patient should be advised to wash the face and hair regularly in order to reduce excess oils. Ideally, this should be done on a daily basis. The use of specialized facial scrubs or shampoos containing miticidal agents such as tea tree oil or permethrin may offer added benefit. Permethrin 5% cream, which is most commonly used for scabies treatment, may help to diminish stubborn Demodex reservoirs in patients with persistent or recurrent issues. This cream is typically applied to the face in the evenings, several times per week.31 Due to toxicity, it should not be used on or near the eyelids.

Clinical Pearls

Clinical recognition of demodicosis can be challenging, as lid and lash debris are typically attributed to Staphylococcal or seborrheic blepharitis.

Demodex mites are virtually impossible to view at the slit lamp due to their transparent nature, small size, aversion to bright light and tendency to remain buried within the lash follicle. Pulling two or three lashes and viewing them under a high magnification microscope can offer confirming evidence of these organisms in many cases. If a microscope is not available, lash rotation under the slit lamp can often help with the diagnosis. Rotating a lash in a circular fashion in the follicle can irritate the Demodex organisms and cause them, along with their debris, to evacuate the follicle.

The hallmark finding of demodicosis is the presence of cylindrical dandruff at the base of the eyelashes.

MGD may also be associated with demodicosis. Demodex mites have been identified as a risk factor for rosacea, and there may be a causative link.4,32,33

Improved lid hygiene is the primary goal in managing any form of blepharitis, including ocular demodicosis.

50% TTO is generally used for in-office treatment only, while 10% solutions are recommended for home use. For those patients who cannot or prefer not to formulate their own concoctions, single-use commercial products such as Cliradex or Blephadex eyelid wipes are available.

1. Zhao YE, Peng Y, Wang XL, et al. Facial dermatosis associated with Demodex: a case-control study. J Zhejiang Univ Sci B. 2011;12(12):1008-15.

2. Hsu CK, Hsu MM, Lee JY. Demodicosis: a clinicopathological study. J Am Acad Dermatol. 2009;60(3):453-62.

3. Ríos-Yuil JM, Mercadillo-Perez P. Evaluation of Demodex folliculorum as a risk factor for the diagnosis of rosacea in skin biopsies. Mexico’s General Hospital (1975-2010). Indian J Dermatol. 2013;58(2):157.

4. Forton FM. Papulopustular rosacea, skin immunity and Demodex: pityriasis folliculorum as a missing link. J Eur Acad Dermatol Venereol. 2012;26(1):19-28.

5. Chen W, Plewig G. Human demodicosis: revisit and a proposed classification. Br J Dermatol. 2014 Jan 28. [Epub ahead of print].

6. Wesolowska M, Knysz B, Reich A, et al. Prevalence of Demodex spp. in eyelash follicles in different populations. Arch Med Sci. 2014;10(2):319-24.

7. Gao YY, Di Pascuale MA, Li W, et al. High prevalence of Demodex in eyelashes with cylindrical dandruff. Invest Ophthalmol Vis Sci. 2005;46(9):3089-94.

8. Coston TO. Demodex folliculorum blepharitis. Trans Am Ophthalmol Soc. 1967;65:361-92.

9. Mastrota KM. Method to identify Demodex in the eyelash follicle without epilation. Optom Vis Sci. 2013;90(6):e172-4.

10. Liu J, Sheha H, Tseng SC. Pathogenic role of Demodex mites in blepharitis. Curr Opin Allergy Clin Immunol. 2010;10(5):505-10.

11. Liang L, Ding X, Tseng SC. High prevalence of Demodex brevis infestation in chalazia. Am J Ophthalmol. 2014;157(2):342-348.e1.

12. Huang Y, He H, Sheha H, Tseng SC. Ocular demodicosis as a risk factor of pterygium recurrence. Ophthalmology. 2013;120(7):1341-7.

13. Kamoun B, Fourati M, Feki J, et al. Blepharitis due to Demodex: myth or reality? J Fr Ophtalmol. 1999;22(5):525-7.

14. Türk M, Oztürk I, Sener AG, et al. Comparison of incidence of Demodex folliculorum on the eyelash follicule in normal people and blepharitis patients. Turkiye Parazitol Derg. 2007;31(4):296-7.

15. Patel KG, Raju VK. Ocular demodicosis. W V Med J. 2013;109(3):16-8.

16. Hom MM, Mastrota KM, Schachter SE. Demodex. Optom Vis Sci. 2013;90(7):e198-205.

17. De Venecia AB, Siong RL. Demodex sp. infestation in anterior blepharitis, meibomian gland dysfunction, and mixed blepharitis. Philipp J Ophthalmol. 2011;36(1):15-22.

18. Lacey N, Kavanagh K, Tseng SC. Under the lash: Demodex mites in human diseases. Biochem (Lond). 2009 Aug 1;31(4):2-6.

19. Gao YY, Di Pascuale MA, Elizondo A, Tseng SC. Clinical treatment of ocular demodecosis by lid scrub with tea tree oil. Cornea. 2007;26(2):136-43.

20. Kim JH, Chun YS, Kim JC. Clinical and immunological responses in ocular demodecosis. J Korean Med Sci. 2011;26(9):1231-7.

21. Kim JT, Lee SH, Chun YS, Kim JC. Tear cytokines and chemokines in patients with Demodex blepharitis. Cytokine. 2011;53(1):94-9.

22. Inceboz T, Yaman A, Over L, et al. Diagnosis and treatment of demodectic blepharitis. Turkiye Parazitol Derg. 2009;33(1):32-6.

23. Fulk GW, Murphy B, Robins MD. Pilocarpine gel for the treatment of demodicosis—a case series. Optom Vis Sci. 1996;73(12):742-5.

24. Gao YY, Di Pascuale MA, Li W, et al. In vitro and in vivo killing of ocular Demodex by tea tree oil. Br J Ophthalmol. 2005;89(11):1468-73.

25. Gao YY, Xu DL, Huang lJ, et al. Treatment of ocular itching associated with ocular demodicosis by 5% tea tree oil ointment. Cornea. 2012;31(1):14-7.

26. Koo H, Kim TH, Kim KW, et al. Ocular surface discomfort and Demodex: effect of tea tree oil eyelid scrub in Demodex blepharitis. J Korean Med Sci. 2012;27(12):1574-9.

27. Tighe S, Gao YY, Tseng SC. Terpinen-4-ol is the most active ingredient of tea tree oil to kill Demodex mites. Transl Vis Sci Technol. 2013;2(7):2. Epub 2013 Nov 13.

28. Holzchuh FG, Hida RY, Moscovici BK, et al. Clinical treatment of ocular Demodex folliculorum by systemic ivermectin. Am J Ophthalmol. 2011;151(6):1030-1034.e1.

29. Salem DA, El-Shazly A, Nabih N, et al. Evaluation of the efficacy of oral ivermectin in comparison with ivermectin-metronidazole combined therapy in the treatment of ocular and skin lesions of Demodex folliculorum. Int J Infect Dis. 2013 May;17(5):e343-7.

30. STROMECTOL [package insert]. Whitehouse Station, NJ: Merck & Co; 2009.

31. Stephenson M. Blepharitis diagnosis: Don’t forget Demodex. Review of Ophthalmology. 2012;19(9):46,48,50,75.

32. Moravvej H, Dehghan-Mangabadi M, Abbasian MR, Meshkat-Razavi G. Association of rosacea with demodicosis. Arch Iran Med. 2007;10(2):199-203.

33. Zhao YE, Wu LP, Peng Y, Cheng H. Retrospective analysis of the association between Demodex infestation and rosacea. Arch Dermatol. 2010;146(8):896-902.