Ocular Demodicosis (Demodex Infestation)

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Background

Observation of the arachnid Demodex folliculorum has been reported since 1840. This hair follicle mite is the only metazoan organism commonly found in the pilosebaceous components of the eyelid of humans. Coston "opened the eyes" of ophthalmologists when he described 22 patients with demodectic eyelid signs and symptoms.[1]



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Illustration of Demodex folliculorum. Reprinted with permission from Antoine Morin, BIODIDAC, University of Ottawa.

Pathophysiology

D folliculorum (all stages) is found in small hair follicles and eyelash hair follicles. In all forms, immature and adult, it consumes epithelial cells, produces follicular distention and hyperplasia, and increases keratinization leading (in eyelashes) to cuffing, which consists of keratin and lipid moieties. Demodex brevis (all stages) is present in the eyelash sebaceous glands, small hair sebaceous glands, and lobules of the meibomian glands. Adults and immature forms consume the gland cells in all of these loci and, when infestations are heavy, can affect the formation of the superficial lipid layer of the tear film coacervate. Demodectic mites produce histologically observable tissue and inflammatory changes, epithelial hyperplasia, and follicular plugging.

Infestation of the eyelash hair follicle results in easier epilation and more brittle cilia. These mites also serve as vectors of infective elements and interrupt tissue integrity. They have been implicated in meibomian granulomas and are associated with certain dermatologic changes. All reported histologic sections of lid follicles infested with D folliculorum show distention and thickening. Coston claims that less than one half of the specimens he observed showed perifollicular lymphocytic infiltration.[1]

Follicular inflammation produces edema and results in easier epilation of the eyelashes. It also affects cilia construction, and lashes are observed to be more brittle in the presence of demodicosis. Madarosis (loss of lashes) is associated with abundant mites, the loss of eyelashes as a result of intercellular edema in the hair shaft, and loss of hair resiliency. Although epithelial hyperplasia associated with follicular plugging is often encountered, dermal changes seldom extend beyond the perifollicular epidermal area. Once believed to be mite excreta, this plugging is now known to be epithelial hyperplasia with interspersed layers of lipid. The formation of a collar of tissue around the base of the lashes is observed clinically. This occurs significantly more often in follicles infected with D folliculorum. The epithelial hyperplasia is hypothesized to be most likely a product of the abrasive action of the mite's claws.

Accumulation of waste material of the follicle mite may occur in affected follicles or sebaceous glands. Electron micrographs of the mite surface and feces show bacterial, viral, and rickettsial elements. Specific reports have revealed that both species pierce epithelial cells and consume cytoplasm. Only D brevis has been observed with channels burrowed to the germinal epithelium in the sebaceous glands.

Demodex species-induced pathologic changes have been implicated in dry eye conditions. When follicular plugging involves the meibomian gland (D brevis) or the gland of Zeis (D folliculorum or D brevis), reduction of the superficial lipid layer of the tear film occurs. The effect of D brevis on the meibomian structure has been implicated in chalazion formation. Chalazia are granulomatous inflammation of the meibomian glands, made of an organized core of epithelioid cells and histocytes surrounded by fibroblasts, lymphocytes, and plasma cells. These defense cells encircle particles too large for normal macrophages to engulf. D brevis has been observed in the center of these meibomian granulomas. Lid infestation by the Demodex species may or may not accompany dermatologic changes of the nose, the cheek, or the forehead.

D folliculorum has been suggested as a factor in pityriasis folliculorum. This dermal inflammation manifests itself as a diffuse erythema of the affected areas; scaly, dry skin; and, in certain cases, rosacealike lesions. The dry skin cycle described by Ayres is initiated when the demodectic mite plugs the follicle and reduces the sebaceous outflow, which leads to scaling as well as rough and dry skin texture.[2] Sebaceous outflow is further reduced when patients inadvertently decide to apply facial cream. The mite flourishes in this environment of oily additives, leading to an increase in the population of the mites and a continuation of the dry skin cycle.

Epidemiology

Frequency

International

Several individuals have attempted to estimate the prevalence of D folliculorum in the eyelash follicles. The initial report in 1961 suggested a prevalence of 95%.[3]

Mortality/Morbidity

Madarosis (loss of lashes) may result from untreated demodicosis.

Race

No racial predilection has been observed.

Sex

Infestation by these parasites is equal in males and females. Infestation is correlated to the number of sebaceous glands but not to the density of the hair follicles.

Age

Post reported that D folliculorum was observed in 84% of the sample population with a mean age of 61 years and in 100% of those older than 70 years.[4] Liang L et al[5] reported in 2010 that ocular demodicosis should be considered as a potential cause of pediatric (2.5-11 years) refractory blepharoconjunctivitis.

Prognosis

The prognosis of symptomatic relief from D folliculorum is very good.

Previous clinical experience shows that total eradication is unlikely, but the mite population can be brought down to an acceptable level with little effort and easily maintained with proper hygiene.

There are promising reports of total eradication with the use of tea tree oil, terpinon-4-ol, and ivermectin 1% cream.

Recurrence of the symptoms is possible if proper hygienic measures are not used.

Patient Education

The suggested home treatment, including the eyelash scrub technique, should be demonstrated to the patient, as follows:

To the eye care professional, the presence of Demodex species together with signs or symptoms of lid inflammation is of greater concern than the prevalence of Demodex species in a general population.

Tea tree oil and tea tree oil shampoo may be purchased from specialty shops locally and online.

History

Symptoms of demodicosis include ocular irritation, itching, and scaling of lids. Past ocular history may include recurrent failed treatment of blepharitis.

Physical

Gross observation may reveal the following:

Slit-lamp findings are as follows:

Causes

Demodex species specific to humans occupy 2 periocular sites hidden from external observation. They are small in size and possess the ability to move across the skin surface.

D folliculorum is found in hair and eyelash follicles associated with pilosebaceous glands in the eye or elsewhere on the face and the body. A single follicle may contain as many as 25 D folliculorum organisms.

D brevis leads a much more solitary lifestyle in sebaceous glands of the body and in the meibomian gland and the gland of Zeis.

D folliculorum measures 0.3-0.4 mm in length, whereas D brevis is one half the size of D folliculorum (0.15-0.2 mm) with similar structure of the head and the thorax but a shorter abdomen.

The 8 legs of this arachnid are segmented and provide locomotion at a rate of 8-16 mm/h.

D folliculorum and D brevis, also known as follicle mites, are believed to be more active in the dark, although capture in daylight is possible.

The bright light of the day and especially the biomicroscope cause the mite to recede back into the follicle. Therefore, the mite can be observed only when an epilated lash is observed under a low-power microscope.

The life stages of D folliculorum begin with copulation at the mouth of the follicle. Reproduction is believed to occur in darkness; a fact that is significant in symptomatology and treatment.

Following copulation, the female burrows back into the follicle near the opening of the pilosebaceous gland and lays her eggs.

Spickett reported the life cycle of D folliculorum and estimated that only 14.5 days elapse from ovum to adult stage, including 120 hours as an adult. Females may live an additional 5 days after oviposition.[3]

Sexes are separate; sexual maturity is reached in the larval form (neoteny).

Females are territorial; they remain in their respective follicles and wait for the nomadic philandering males that travel over the surface of the skin from one follicle to another in seek of females.

Adults reside in the follicle parallel to the hair shaft, head inward, often with the tail end (opisthosoma) protruding onto the surface of the skin at the base of the eyelash.

Laboratory Studies

Diagnosis of demodicosis is made on a high index of clinical suspicion.

Occasionally, nasal skin scrapings may be requested to rule out the possibility of acne rosacea.

Imaging Studies

By visualizing the metazoan parasite under high-power magnification, a definitive diagnosis can be made.

Imaging systems using high magnification that allow photographic documentation and grading of demodicosis are now commercially available.

An epilated lash examined under low-power magnification may demonstrate the organism.

Adding a fluorescein solution after mounting further helps in detecting and counting the mites that are embedded in cylindrical dandruff of epilated eyelashes.[7]

Electron microscopy has been used to visualize the organism.

Procedures

Slit lamp biomicroscopy involves carefully removing a collarette, at the base of an eyelash, using flat ophthalmic forceps. The tail of a Demodex may be visualized as a translucent strand at 16x magnification.

Histologic Findings

All reported histologic sections of lid follicles infested with D folliculorum show distention and thickening. Coston claims that less than half the specimens he observed showed perifollicular lymphocytic infiltration.[1] Follicular inflammation produces edema and results in easier epilation of the eyelashes. It also affects cilia construction, and the lashes are observed to be more brittle in the presence of demodicosis. Dermal changes seldom extend beyond the perifollicular epidermal area, although epithelial hyperplasia associated with follicular plugging is often encountered.



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Eyelid section shows Demodex folliculorum (M) in the hair follicle. Note mite mouthparts (arrow) embedded in epithelium and straplike layers of kerati....



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Section of sebaceous gland of an eyelash shows Demodex brevis (M). Note gland cell (C) destruction (McManus, X375). Reprinted with permission from Els....



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Cross-section through small hair follicle of the eyelid. Note distension, hyperplasia, and moderate epithelial keratinization caused by the activities....



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Section of eyelid shows eyelash (L), cuffing (C), and small segment of Demodex folliculorum (M). Note layering of cuff (Masson, X275). Reprinted with ....



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Demodex folliculorum.



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Demodex along the shaft of the cilia.



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Demodex along the shaft of the cilia (higher magnification).

Medical Care

Note that none of the treatment suggestions for Demodex blepharitis has been FDA approved.

Historical management of Demodex blepharitis involves a treatment regimen that is divided into in-office care and at-home care.

In the office, D folliculorum can be lured to the follicle surface with the use of volatile fluids, such as ether (not allowed in the United States), brushed vigorously across the external lid margin, following 0.5% proparacaine instillation. Five minutes later, a solution of 70% alcohol is applied in a similar manner. This regimen is reported to successfully reduce both the symptoms and the observed number of mites by the end of 3 weekly visits. Ether and alcohol should be used with caution, and corneal contact should be prevented.

A combination of this in-office treatment with a home regimen is suggested. The home regimen includes scrubbing the eyelids twice daily with baby shampoo diluted with water to yield a 50% dilution and applying an antibiotic ointment at night until resolution of symptoms.

A novel in-office treatment using a mechanical rotating handpiece with a microsponge tip combined with polyaminopropyl biguanide foam solution removes oil, scurf, and debris; exfoliates the eyelids; and claims to decrease Demodex infestation.[8]



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A novel in-office treatment using a mechanical rotating handpiece with a microsponge tip combined with PolyaminopropylBiguanide foam solution removes ....

Various treatments have been used to control Demodex mites. Most treatments 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.

Mercury oxide 1% ointment is frequently used.

Pilocarpine gel reduced the number of mites and alleviated the symptom of itching in 11 patients in a nursing home. Celerio et al hypothesized that pilocarpine was directly toxic to the mites because its muscarinic action impedes respiration and motility.[9]

Ivermectin 1% cream

Ivermectin 1% cream (Soolantra, Galderma Labs) has been approved by the FDA for the treatment of rosacea. It may be applied to eyelashes and eyelids once daily. It may have beneficial effects as early as 2 weeks and may be used safely up to 52 weeks, depending on the severity of the Demodex infestation.

Tea tree oil and terpinon-4-ol

Prior to treatment with terpinon-4-ol (Cliradex, a natural tea tree oil product), 50% tea tree oil with Macadamia nut oil was the most popular treatment method. This is applied with cotton tip applicators, after one drop of tetracaine.[10, 11, 12, 5] Aggressively debride the lashes and the lash roots first with scrubs. Try to get the oil into the lash roots and along the lashes to kill any eggs. Treat the eyebrows as well. Three applications, 10 minutes apart, per visit are recommended; treatment is completed with compounded 20% tea tree ointment. Repeat for 3 visits, each one week apart.

Gao et al[13] reported in 2012 that there is a strong correlation between symptomatic resolution and reduction of Demodex counts by daily massage with 5% tea tree oil ointment.[5]

Home regimen includes the following:

The latest promising treatment regimen includes the use of Cliradex, a commercially available natural product, isolating terpinon-4-ol from tea tree oil. A medicated towelette is used twice daily as an eyelid and eyelash wipe.

A double-blinded randomized clinical trial comparing two tea tree oil–based formulations in patients with chronic blepharitis showed improved ocular surface parameters in both study groups and reduced cytokines and Demodex count in the group who received advanced gel containing 3% tea tree oil plus essential oils and vitamins.[15] However, no comparison was done with placebo.

A systematic review and meta-analysis of treatment efficacy for Demodex blepharitis showed that local treatments continue to be promising.[16]

 

Consultations

Weekly follow-up visits for 4 weeks may be necessary in severe cases to monitor the effects of in-office and at-home treatment regimen.

Further Outpatient Care

Terpinon-4-ol (Cliradex) may be purchased as a home care kit. In the absence of Cliradex, the following outpatient care may be followed:

Inpatient & Outpatient Medications

See the list below:

Medication Summary

Various treatments have been used to control Demodex mites. Most treatments 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. A tea tree oil product (Cliradex) can be used.[14] Terpinen-4-ol is the most active component of tea tree oil.

Erythromycin ophthalmic (Ilotycin)

Clinical Context:  Belongs to the macrolide group of antibiotics. Basic and readily forms a salt when combined with an acid. Inhibits protein synthesis without affecting nucleic acid synthesis.

Used for the treatment of ocular infections involving the lids, conjunctiva, and/or cornea caused by organisms susceptible to it.

Mercury oxide 1% ointment

Clinical Context:  For infestation of eyelashes; inspect eyelids and mechanically remove nits. This compound may be ordered from Leiter's Park Avenue Pharmacy and Professional Compounding Center (Leiter's Park Avenue Pharmacy).

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of this clinical setting.

Pilocarpine ophthalmic (Pilopine HS 4%, Isopto Carpine)

Clinical Context:  Produces miosis through contraction of iris sphincter muscle, which pulls iris root away from trabecular meshwork in angle-closure glaucoma and allows aqueous humor to exit eye, thereby lowering IOP. Also causes ciliary muscle contraction, resulting in accommodation and increased tension on and opening of trabecular meshwork spaces, facilitating aqueous humor outflow and lowering IOP in open-angle glaucoma.

Class Summary

Dosage and frequency of administration must be individualized. Patients with darkly pigmented irides may require higher strengths of pilocarpine.

Ivermectin topical (Sklice, Soolantra)

Clinical Context:  Pediculicide derived from fermentation of a soil-dwelling actinomycete, Streptomyces avermitilis.

Causes parasite death by selective, high-affinity binding to glutamate-gated chloride channels located in invertebrate nerve and muscle cells; this results in increased cell membrane permeability to chloride ions with hyperpolarization of the nerve or muscle cells, and ultimately parasite paralysis and death.

Ivermectin cream (Soolantra) has both anti-inflammatory and antiparasitic activity.

Class Summary

Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Author

Manolette R Roque, MD, MBA, FPAO, Section Chief, Ocular Immunology and Uveitis, Department of Ophthalmology, Asian Hospital and Medical Center; Section Chief, Ocular Immunology and Uveitis, International Eye Institute, St Luke's Medical Center Global City; Senior Eye Surgeon, The LASIK Surgery Clinic; Director, AMC Eye Center, Alabang Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Barbara L Roque, MD, DPBO, FPAO, Senior Partner, Roque Eye Clinic; Chief of Service, Pediatric Ophthalmology and Strabismus Section, Department of Ophthalmology, Asian Hospital and Medical Center; Active Consultant Staff, International Eye Institute, St Luke's Medical Center Global City

Disclosure: Nothing to disclose.

C Stephen Foster, MD, FACS, FACR, FAAO, FARVO, Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Aldeyra Therapeutics (Lexington, MA); Bausch & Lomb Surgical, Inc (Rancho Cucamonga, CA); Eyegate Pharma (Waltham, MA); Novartis (Cambridge, MA); pSivida (Watertown, MA); Xoma (Berkeley, CA); Allakos (Redwood City, CA)<br/>Serve(d) as a speaker or a member of a speakers bureau for: Alcon (Geneva, Switzerland); Allergan (Dublin, Ireland); Mallinckrodt (Staines-upon-Thames, United Kingdom)<br/>Received research grant from: Alcon; Aldeyra Therapeutics; Allakos Pharmaceuticals; Allergan; Bausch & Lomb; Clearside Biomedical; Dompé pharmaceutical; Eyegate Pharma; Mallinckrodt pharmaceuticals; Novartis; pSivida; Santen; Aciont.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Avedro; Bio-Tissue; Shire<br/>Received income in an amount equal to or greater than $250 from: AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab.

Chief Editor

Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Fernando H Murillo-Lopez, MD, Senior Surgeon, Unidad Privada de Oftalmologia CEMES

Disclosure: Nothing to disclose.

Acknowledgements

The author was a fellow and affiliated with the Ocular Immunology and Uveitis Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, while performing this work.

References

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  2. Ayres S Jr. Demodex folliculorum as a pathogen. Cutis. 1986 Jun. 37(6):441. [View Abstract]
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  14. Cliradex instructional video. Available at http://www.youtube.com/v/OljcnbghoR8?hl=en&fs=1
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Illustration of Demodex folliculorum. Reprinted with permission from Antoine Morin, BIODIDAC, University of Ottawa.

Backsides of numerous pubic crabs with infestation of the lashes and secondary blepharitis. Reprinted with permission from HD Riley, OD, Indiana University School of Optometry.

Phthiriasis (Phthirus pubis) pubic crab lash infestation and secondary blepharitis. Reprinted with permission from HD Riley, OD, Indiana University School of Optometry.

Phthiriasis (pubic lice). Reprinted with permission from HD Riley, OD, Indiana University School of Optometry.

Eyelid section shows Demodex folliculorum (M) in the hair follicle. Note mite mouthparts (arrow) embedded in epithelium and straplike layers of keratin (hematoxylin and eosin, X400). Reprinted with permission from Elsevier Science.

Section of sebaceous gland of an eyelash shows Demodex brevis (M). Note gland cell (C) destruction (McManus, X375). Reprinted with permission from Elsevier Science.

Cross-section through small hair follicle of the eyelid. Note distension, hyperplasia, and moderate epithelial keratinization caused by the activities of Demodex folliculorum (arrow) (hematoxylin and eosin, X375). Reprinted with permission from Elsevier Science.

Section of eyelid shows eyelash (L), cuffing (C), and small segment of Demodex folliculorum (M). Note layering of cuff (Masson, X275). Reprinted with permission from Elsevier Science.

Demodex folliculorum.

Demodex along the shaft of the cilia.

Demodex along the shaft of the cilia (higher magnification).

A novel in-office treatment using a mechanical rotating handpiece with a microsponge tip combined with PolyaminopropylBiguanide foam solution removes oil, scurf, and debris; exfoliates the eyelids, and claims to decrease Demodex infestation. Image courtesy of Rendia, Inc. Copyright 2017 Rendia, Inc.

Illustration of Demodex folliculorum. Reprinted with permission from Antoine Morin, BIODIDAC, University of Ottawa.

Eyelid section shows Demodex folliculorum (M) in the hair follicle. Note mite mouthparts (arrow) embedded in epithelium and straplike layers of keratin (hematoxylin and eosin, X400). Reprinted with permission from Elsevier Science.

Section of sebaceous gland of an eyelash shows Demodex brevis (M). Note gland cell (C) destruction (McManus, X375). Reprinted with permission from Elsevier Science.

Cross-section through small hair follicle of the eyelid. Note distension, hyperplasia, and moderate epithelial keratinization caused by the activities of Demodex folliculorum (arrow) (hematoxylin and eosin, X375). Reprinted with permission from Elsevier Science.

Section of eyelid shows eyelash (L), cuffing (C), and small segment of Demodex folliculorum (M). Note layering of cuff (Masson, X275). Reprinted with permission from Elsevier Science.

Demodex folliculorum.

Demodex along the shaft of the cilia.

Demodex along the shaft of the cilia (higher magnification).

Backsides of numerous pubic crabs with infestation of the lashes and secondary blepharitis. Reprinted with permission from HD Riley, OD, Indiana University School of Optometry.

Phthiriasis (Phthirus pubis) pubic crab lash infestation and secondary blepharitis. Reprinted with permission from HD Riley, OD, Indiana University School of Optometry.

Phthiriasis (pubic lice). Reprinted with permission from HD Riley, OD, Indiana University School of Optometry.

Demodex infestation is an under diagnosed cause of chronic blepharitis. Image courtesy of Rendia, Inc. Copyright 2017 Rendia, Inc.

Blepharitis secondary to Demodex infestation. Image courtesy of Rendia, Inc. Copyright 2017 Rendia, Inc.

A novel in-office treatment using a mechanical rotating handpiece with a microsponge tip combined with PolyaminopropylBiguanide foam solution removes oil, scurf, and debris; exfoliates the eyelids, and claims to decrease Demodex infestation. Image courtesy of Rendia, Inc. Copyright 2017 Rendia, Inc.