Smite the Mite: Current and Emerging Treatments for Demodex Blepharitis

In 2022, the American Journal of Managed Care published an article about the misdiagnosis and underdiagnosis of Demodex blepharitis (DB) and the unmet need to manage DB patients.¹

This, along with the development of new medications, treatments, and continuing education courses, has encouraged eyecare professionals to take a closer look at the mites, which have become notoriously associated with chronic blepharitis and dry eye disease.

Whether you’ve seen the misleadingly adorable Demodex stuffed toy at a conference, been approached by an XDEMVY rep, or caught the latest on Demodex treatment at a continuing education course, you have probably heard of these tiny mites and their ability to cause problems for the eyelids.

But do you know how to tackle Demodex in your chair? Here is the latest on Demodex blepharitis, including its connection with dry eye disease and treatment options.

Demodex at a glance

Demodex mites live in human hair follicles, including the eyelids and eyelashes, and are some of the trillions of microorganisms that reside in the human body.¹

There are two subtypes of Demodex:¹

Demodex folliculorum feed on skin cells and are associated with anterior blepharitis.
Demodex brevis feeds on sebum and contributes to posterior blepharitis. They are associated with meibomian gland dysfunction (MGD) and keratoconjunctivitis.

While they are considered part of our natural microflora in normal concentrations, overproliferation of Demodex in the eyelids leads to Demodex blepharitis.

Prevalence

Studies have shown that Demodex blepharitis affects approximately 25 million Americans, with observational studies reporting that it affects close to 60% of the population.² A study by Akkucuk et al. confirmed that the presence of Demodex was higher in groups who suffered from blepharitis and chalazia.³

Risk factors

While anyone can get demodex blepharitis, research shows that several risk factors increase the risk of Demodex overproliferation including:⁴

Advanced age
Rosacea
Diabetes
Immunodeficiency
Dry eye disease (DED) due to MGD
Stress
Smoking
High alcohol intake
Sun exposure

Demodex and dry eye disease

Demodex blepharitis is strongly associated with dry eye disease, specifically dry eye disease with a meibomian gland dysfunction component.⁵ Overproliferation of Demodex brevis, in particular, has been implicated in meibomian gland loss.⁶

Research suggests a cycle wherein Demodex waste can clog glands, leading to changes in gland architecture and inflammation, which, in turn, thickens the meibum produced by the glands, thereby creating an even more favorable environment for the mites to infest.⁷

In addition to impacting the structure and function of meibomian glands, Demodex waste also causes hypersensitivity, exacerbating ocular surface inflammation and dry eye symptoms.⁸

Moreover, a 2023 review article published in Eye & Contact Lens: Science & Clinical Practice notes that patients who used common anti-inflammatory treatments such as lifitegrast and cyclosporine, which tackle dry-eye-associated inflammation, were just as likely to present with Demodex blepharitis compared to those who did not use topical immunomodulators.³

Need some tips on how to discuss Demodex blepharitis with patients? Check out Overcoming Mite Fright: How to Talk to Patients about Demodex Blepharitis!

Diagnosing Demodex blepharitis

Demodex blepharitis can be diagnosed via a slit lamp examination of the upper and lower lashes. While definitive diagnosis is made by examining an epilated lash under a microscope to look for either Demodex mites or their waste products, cylindrical sheathing of the lashes, known as collarettes, is considered pathognomonic for Demodex infestation.²

The amount of collarettes seen under a slit lamp correlates with the severity of the infestation. Treatment is recommended if more than 10 collarettes are seen across both upper eyelids, or about five per upper eyelid.^2,9 However, the presence of fewer than five collarettes per eye, especially coupled with symptoms like itching, can still signal early Demodex infestation.⁸

An article from Contact Lens & Anterior Eye published in 2020 suggested a new approach to evaluating Demodex in the clinic, which involves removing the collarettes and moving the eyelash aside with forceps, without epilation, to observe the tails of the Demodex mites that are present within the lash follicle.²

Figure 1: Slit lamp image of Demodex blepharitis, as shown by collarettes on the lid margin.

^{Figure 1: Courtesy of Cory Lappin, OD, MS, FAAO.}

Current treatment options for Demodex blepharitis

We currently have several treatments for Demodex blepharitis that can be administered both at home by the patient and in the office by the eyecare provider.

Over-the-counter lid cleansers

Lid cleansers, particularly those infused with tea tree oil, were once the standard of care for Demodex and other types of blepharitis. These include tea-tree oil-based wipes like OcuSoft, sprays like We Love Eyes and Zocular, and okra-based cleansers, which can help kill Demodex. These are considered modestly effective in eliminating Demodex and are often coupled with other therapies.

Considerations for over-the-counter lid cleansers:

Pros: Relatively low price point and easy for patients to obtain
Cons: Lifelong use can lead to compliance and toxicity issues

Ointments and oral therapies

Ointments for Demodex include antibiotic steroid ointments, topical metronidazole, and ivermectin ointment. Topical ivermectin 1% cream, applied carefully to the eyelid margins at night for 6 to 8 weeks, can be used in conjunction with other therapies.

Ivermectin works by targeting glutamate-gated chloride channels, causing paralysis and ultimately leading to the death of the mites. Steroid ointments and topical metronidazole can be used to relieve blepharitis symptoms; however, these do not specifically target the Demodex.

Oral ivermectin 200 mcg/kg as a single dose, repeated in 7 days, when any remaining Demodex eggs would have hatched, is an off-label but effective option for severe or treatment-resistant Demodex blepharitis.

Considerations for ointments and oral therapies:

Pros: These can be effective in reducing Demodex load
Cons: Both topical ointments and oral therapies are known to have side effects, such as blurry vision for topical therapies and stomach upset for oral therapies, with a greater likelihood of side effects presenting with oral therapies like ivermectin

XDEMVY

XDEMVY (lotilaner ophthalmic solution 0.25%, Tarsus Pharmaceuticals) is an FDA-approved drop explicitly developed to combat Demodex. Originally developed from veterinary drugs to combat mites in animals, XDEMVY is currently FDA-approved for the treatment of Demodex blepharitis. XDEMVY involves a 6-week course with the drop being instilled twice daily by the patient.

Considerations for XDEMVY:

Pros: The drop is relatively easy to use, and most patients are familiar with using eye drops
- XDEMVY is highly effective and non-toxic
Cons: Many insurance companies do not cover XDEMVY or make coverage difficult, and the high drop cost limits the patient’s ability to pay out of pocket
- Some patients may need more than one course of XDEMVY

To learn more about XDEMVY's impact on concurrent DB and MGD, check out Demodex Blepharitis and MGD: New Data on Lotilaner Ophthalmic Solution!

Cleansing systems

BlephEx, Zest, and NuLids are popular eyelid cleansing systems. BlephEx, an in-office procedure, uses a rotating micro-sponge to remove debris, including collarettes, from the eyelids. Zest (Zocular Eyelid System Treatment), also an in-office system, uses an okra-based gel to cleanse eyelids and soothe eyes.

NuLids is a handheld device that vibrates to remove debris and gently massages the eyelid margin to improve meibomian gland function. Unlike BlephEx and Zest, NuLids can be used in the office and by the patient at home.

Considerations for cleansing systems:

Pros: Cleansing systems help reduce the load of Demodex mites, and most patients feel an immediate improvement in symptoms
Cons: These can carry high costs and are often not covered by insurance; with NuLids, which can be used at home, there is also a risk of poor compliance with treatment.

Intense pulse light (IPL) therapy

While technically considered off-label, intense pulse light (IPL) therapy has been shown to reduce Demodex density and improve ocular surface parameters associated with meibomian gland dysfunction.

Considerations for IPL:

Pros: Tackling both Demodex and meibomian gland dysfunction in a single treatment
Cons: IPL cannot be performed on darker skin tones, specifically Fitzpatrick V and VI, and carries a high out-of-pocket cost for patients, with practices charging anywhere from $400 to $600 per single treatment

5 key takeaways

Demodex blepharitis is common and accounts for more than half of blepharitis cases,² but it remains underdiagnosed by eyecare providers
While Demodex mites naturally live on humans, their overproliferation leads to blepharitis, exacerbates dry eye symptoms, and may even contribute to the mechanism associated with meibomian gland dysfunction
Although there are several ways to check for Demodex, collarettes are considered pathognomonic for Demodex infestation
Several treatment options exist for Demodex blepharitis, including lid cleansers, ointments, drops, and IPL
XDemvy is the first FDA-approved drop to effectively eliminate Demodex mites and is effective but costly, making it difficult to obtain through insurance or out of pocket

While Demodex blepharitis remains a problem, we now have various tools to help our patients manage this condition. The challenge now is to ensure that practitioners know about these treatments and that patients can access them through their insurance.