Ocular Demodicosis (Demodex Infestation)

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, 2]

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 specific 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.[2]

Follicular inflammation produces edema and results in easier epilation of the eyelashes. It also affects cilia construction, and lashes are more brittle in the presence of demodicosis. Madarosis (loss of lashes) is associated with abundant mites, the loss of eyelashes due to intercellular edema in the hair shaft, and loss of hair resiliency. Although epithelial hyperplasia associated with follicular plugging often is encountered, dermal changes seldom extend beyond the perifollicular epidermal area. Once believed to be mite excreta, this plugging now is known to be epithelial hyperplasia with interspersed lipid layers. 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 as diffuse erythema of the affected areas; scaly, dry skin; and, in some instances, rosacea-like lesions. The dry skin cycle described by Ayres is initiated when the demodectic mite plugs the follicle and reduces the sebaceous outflow, leading to scaling and rough and dry skin texture.[3] 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.

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%.[4]

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 100% of those older than 70.[5] Liang L et al[6] reported in 2010 that ocular demodicosis should be considered as a potential cause of pediatric (2.5-11 years) refractory blepharoconjunctivitis.

The prognosis of symptomatic relief from D folliculorum is excellent.

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.

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

• Soak the washcloth in warm water, and wring it.

• Apply enough baby shampoo to form a lather on the washcloth.

• With the eye closed, massage the lashes on the lid margin, moving from left to right 15 times. (Do not touch the eye itself.) Repeat on the other eye.

• Rewet the cloth, and rinse off the shampoo.

• Squeeze 1 inch of the ointment onto the index finger and gently rub into the lashes with the eye closed. Repeat on the other eye.

To the eye care professional, the presence of Demodex species, together with signs or symptoms of lid inflammation, is of a more significant 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.

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

Gross observation may reveal the following:

• Lid thickening

• Scaling of lids

• Madarosis (loss of lashes)

• Conjunctival inflammation

• Meibomian gland dysfunction

• Rosacea: The results of the study by Moravvej et al[7] conclude that the prevalence and the number of Demodex mites in rosacea patients are higher than in control subjects, supporting the pathogenic role of Demodex mites in rosacea.

• Decreased vision

Slit-lamp findings are as follows:

• A collar of tissue around the base of the eyelashes

• Follicular distention

• Dry eye

• Cornea - Superficial corneal vascularization, marginal corneal infiltration, phlyctenule-like lesion, superficial corneal opacity, nodular corneal scar

Demodex species specific to humans occupy two periocular sites hidden from external observation. They are small in size and can 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 the body's sebaceous glands, 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 a similar head and thorax structure but a shorter abdomen.

The eight 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 into the follicle. Therefore, the mite can be observed only when an epilated lash is viewed 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, which is significant in symptomatology and treatment.

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

Spickett reported the life cycle of D folliculorum and estimated that only 14.5 days elapse from the ovum to the adult stage, including 120 hours as an adult. Females may live an additional five days after oviposition.[4]

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

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

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

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.

A definitive diagnosis can be made by visualizing the metazoan parasite under high-power magnification.

Imaging systems using high magnification that allow photographic documentation and grading of demodicosis now are 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 the cylindrical dandruff of epilated eyelashes.[8]

Electron microscopy has been used to visualize the organism.

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.

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.[2] 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.

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.[9]

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.[10]  

Lotilaner ophthalmic 

Lotilaner ophthalmic solution (Xdemvy) was approved by the FDA for treatment of Demodex blepharitis in July 2023. Lotilaner is a gamma-aminobutyric acid (GABA)-gated chloride channel inhibitor selective for mites. Inhibition of these GABA chloride channels causes a paralytic action in the target organism, leading to its death. 

Approval was based on 2 multicenter, randomized controlled trials (SATURN-1 and SATURN-2) in 833 patients. Patients who received active drug in the SATURN-1 trial had a statistically significantly higher collarette cure (81.3% vs 23%), complete collarette cure (44% vs 7.4%), mite eradication (67.9% vs 17.6%), erythema cure (19.1% vs 6.9%), and composite cure (13.9% vs 1%) than the control group (all values P < 0.0001).[31]   

Similarly, in the SATURN-2 trial, patients who received lotilaner achieved a statistically significant (P < 0.0001) collarette cure (56% vs 12.5%), clinically meaningful collarette reduction to 10 collarettes or fewer (89.1% vs 33%), mite eradication (51.8% vs 14.6%), erythema cure (31.1% vs 9%), and composite cure (19.2% vs 4%) than the control group.[32]   

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

Before 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.[6, 11, 12, 13]  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[14] 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.[6]

Home regimen includes the following:

• Use tea tree shampoo on hair and eye lashes every day.
• Use tea tree soap or face wash every day.
• Apply 5% tea tree oil cream/ointment daily to cover the skin around the lids to prevent mating and reinfestation from the skin around the eye. ^[15]
• Buy new makeup and discard old makeup; do not use makeup for 1 week.
• Clean sheets and buy new pillows.
• Check spouse; if both have this problem, both need to be treated.
• Check pets.
• For the first few weeks, use the ointment at night after tea tree shampoo scrubs. If inflammation is present, combination steroid-antibiotic ointments may be applied for one week. This is then replaced with a pure antibiotic ointment or with compounded 10% tea tree ointment.

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.[16] 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.[17]

Intense pulsed light treatment of Meibomian gland dysfunction has been shown to decrease the population of Demodex.[18]  

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.

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

• Eyelash scrubs twice daily with a 50-50 mixture of baby shampoo and water using a cotton swab or a rough washcloth provide symptomatic relief. The assumption that patients are knowledgeable about this procedure should not be made; demonstrating the eyelash scrub technique to the patient may be necessary.

• The patient should be prescribed two 3.5-g tubes of a viscous ointment, preferably an antibiotic ointment, mercuric oxide ointment, or 10% tea tree oil ointment. The patient should be instructed to squeeze out 1 inch of ointment and apply liberally to each lid immediately before bedtime. This is believed to inhibit the reproductive attempts of the adult Demodex. The patient is also instructed to wash out the ointment every morning with the eyelash scrubs.

• Preventive facial hygiene with daily soap and water washes is encouraged. Long-term compliance may be a problem in patients with dry skin.

• Dermatologic consultation may be helpful in a patient with recurrent episodes or in those with accompanying dermatologic involvement.

• Typically, 3-4 weeks of treatment is necessary. In patients who respond to the above outlined treatment, the eyelid scrubs may be reduced to once a day and an ointment at bedtime.

• Consequently, the treatment is reduced until the condition resolves or recurs. If recurrence of symptoms occurs during the tapering period, the patient is advised to go back to the previous treatment level and to continue at that level.

• If the patient is unresponsive to treatment, consider noncompliance or other underlying etiologies.

Inpatient and outpatient medications include the following:

• Lotilaner ophthalmic (Xdemvy)

• Terpinon-4-ol (Cliradex)

• Ivermectin 1% cream (Soolantra)

• 50-50 mixture of baby shampoo and water

• Erythromycin ointment

• Mercury oxide 1% ointment

• Pilocarpine 4% gel

• 10% tea tree oil ointment

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.[15] Terpinen-4-ol is the most active component of tea tree oil. 

The antiparasitic ophthalmic solution lotilaner (Xdemvy) was approved by the FDA for treatment of Demodex blepharitis in July 2023.[31, 32]   

Class Summary

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

Erythromycin ophthalmic (Ilotycin)

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.

Class Summary

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

Pilocarpine ophthalmic (Pilopine HS 4%, Isopto Carpine)

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

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

Ivermectin topical (Sklice, Soolantra)

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.

Lotilaner ophthalmic (Xdemvy)

Gamma-aminobutyric acid (GABA)-gated chloride channel inhibitor selective for mites. Inhibition of these GABA chloride channels causes a paralytic action in the target organism, leading to its death. It is indicated for adults for treatment of Demodex blepharitis.