Disclosures: Farid reports she is a consultant to Tarsus Pharmaceuticals.
April 01, 2021
4 min read

Demodex: Easy to find, not so easy to kill

Disclosures: Farid reports she is a consultant to Tarsus Pharmaceuticals.
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The Demodex mite, of which there are at least 65 species, is the most common microscopic ectoparasite found on human skin. Demodex folliculorum is responsible for Demodex blepharitis, which accounts for at least 45% of blepharitis cases.

Demodex blepharitis refers to inflammation that occurs when there is an infestation of Demodex mites in the eyelash follicles (Figure 1). The condition is widespread, especially among older patients: 84% of people 60 years of age and older and 100% of those older than 70 years have Demodex blepharitis. Younger people are not immune from Demodex, particularly those with rosacea or a compromised immune system. In fact, when 1,121 sequential patients in multiple eye care practices were screened for collarettes, a pathognomonic sign of Demodex blepharitis, they were found in 58% of patients. This means it is possible that 25 million Americans have Demodex blepharitis.

Marjan Farid
Marjan Farid

Without treatment aimed specifically at eradicating Demodex, the mites will continue to proliferate, resulting in a worsening of the condition. It therefore becomes essential that we screen all our patients during the slit lamp exam. It is simple to identify collarettes by having patients direct their gaze downward so we can look for collarettes around the base of the lashes on the upper lid. Collarettes (Figure 2) are the accumulated debris and waste of Demodex mites living in the lash follicles; their existence is a definitive diagnostic indicating infestation. It is worth noting that, as with other types of ocular surface disease, symptoms of Demodex blepharitis often do not correlate with signs. This is particularly the case in the elderly population that comprises most of our patients with cataracts and is demonstrated by my case here.

Demodex folliculorum mites
Figure 1. Cluster of Demodex folliculorum mites embedded in a collarette near the lash follicle.

Source: Tarsus Pharmaceuticals
slit lamp exam
Figure 2. Patient with eyes open at slit lamp (left). Same patient looking down at slit lamp (right).

Source: Tarsus Pharmaceuticals

Case: 72-year-old patient with cataracts

A 72-year-old man, eager to shed his glasses, presented for cataract surgery saying that his vision was getting worse. He noticed it the most at the end of the day, especially after reading or watching television, but he claimed that his eyes felt fine. Upon exam, his best corrected visual acuity was 20/40 in the right eye and 20/50 in the left eye, with 2+ nuclear sclerotic cataracts in both eyes.

Further illustrating the discord between signs and symptoms, the patient had 2+ central punctate keratitis with staining and a tear breakup time of 2 to 3 seconds in both eyes. I noted 1+ meibomian gland dysfunction, as well as significant collarettes along the lash base on both eyes, confirming Demodex blepharitis (Figure 3).

Figure 3. Significant collarettes along the lash base on both eyes, confirming Demodex blepharitis.

Source: Marjan Farid, MD

Frustratingly, the patient chose not to have blepharoexfoliation as he did not believe he had a problem. In my educational discussion with the patient, I explained that the mite infestation increased his risk for infection and complications associated with his cataract surgery. He did agree to postpone cataract surgery and initiate at-home blepharitis treatments consisting of tea tree oil-containing lid scrubs and face wash, hot compresses and preservative-free artificial tears.

After 6 weeks, the patient had cataract surgery. Unfortunately, the procedure exacerbated his ocular surface disease, and he developed more significant symptoms in both eyes, including morning stickiness of the lids, redness and foreign body sensation. I directed him to continue the preoperative regimen he was prescribed, but the patient was noncompliant with lid hygiene. He was unhappy and believed that cataract surgery made his eyes feel even more irritated and uncomfortable.

Treating Demodex blepharitis

That Demodex blepharitis is easily identified is the good news. The bad news is that treatment is a challenge as there is no FDA-approved therapy specifically indicated for Demodex, and the available off-label treatments are not proven. Although we have some success with the options currently at our disposal, these are not curative, and some may even be harmful.

The mainstay therapy of tea tree oil-containing lid scrubs can help control the Demodex population, but the oil’s active component, terpinen-4-ol (T4O), is irritating. New evidence has shown T4O is toxic to meibomian gland epithelial cells. I incorporate in-office blepharoexfoliation for a more effective solution, but it does not kill Demodex mites.

Promising treatment for Demodex blepharitis

A lack of compliance with irritating and inconvenient lid scrubs often creates a situation in which full eradication and a successful outcome are difficult to achieve. Our treatments for Demodex blepharitis are sorely lacking, creating a large unmet need for a safe and effective treatment. This is why I am excited about a new targeted therapeutic in the pipeline designed to address Demodex blepharitis at the root cause.

TP-03 is a novel therapeutic, based on the drug lotilaner, being developed by Tarsus Pharmaceuticals. The drop has been shown to paralyze and eradicate mites and other parasites through the inhibition of parasite-specific GABA-Cl channels. The company has completed four phase 2 clinical trials in which TP-03 met its primary and secondary endpoints and was well tolerated throughout (Figure 4).

baseline compared with day 28
Figure 4. Collarettes, which are pathognomonic of Demodex blepharitis, shown at baseline compared with day 28 in the left eye of a subject in the Mars trial.

Source: Tarsus Pharmaceuticals

In the past, we may not have been seeking out evidence of these common mites and the damage they cause because of our limited treatment options. Soon, we may be able to better care for all patients with Demodex blepharitis and ensure that we set up those prepping for cataract surgery for successful outcomes.