Understanding the Mechanisms and Impact of Demodex Blepharitis

A literature review published in Eye & Contact Lens provided a comprehensive overview of Demodex blepharitis, including its causes, symptoms, diagnostic methods, current treatments, and emerging therapies including lotilaner ophthalmic solution.  

Demodex, a type of mite that infests the eyelashes, becomes more common with age, affecting over 80% of those over 60 years old. However, among younger populations, the prevalence of Demodex is consistently low, ranging from 2% to 27%. 

Demodex mites are commonly found on human skin, especially the cheeks, nose, and eyelids. Two species of Demodex mites, D folliculorum and D brevis, feed on sebum and follicular epithelial cells. When present in higher density, these mites can cause an inflammatory condition called demodicosis. The mites can contribute to blepharitis through direct damage to the hair follicles, acting as vectors for bacteria, and inducing inflammation. They can also trigger an allergic response and disrupt the microbiome in the conjunctival sac. 

Associated risk factors of Demodex blepharitis include rosacea, diabetes, and ageing. Rosacea, a skin condition, is closely linked to ocular Demodex infestation, leading to ocular rosacea and/or Demodex blepharitis. Demodex infestation is also associated with dry eye disease and meibomian gland dysfunction, potentially worsening symptoms and causing structural damage to the meibomian glands. There is also a significant association with conditions such as chalazia, hordeola, and pterygia, particularly in children, suggesting that Demodex should be considered a risk factor for developing these conditions. 

Demodex blepharitis is characterized by the presence of collarettes, cylindrical exudative excretions that form around the base of the eyelash follicle. Collarettes are composed of accumulated material, dead or living mites, and eggs or egg casings. Trichiasis, lash misdirection, and madarosis, eyelash loss, are also common clinical signs of Demodex blepharitis. Patients with demodicosis commonly report ocular itching as their most bothersome symptom, and they may also experience dryness, discharge, redness, burning, tearing, foreign body sensation, pain, and blurred or fluctuating vision.  

Demodex blepharitis can significant impact patient quality of life, including multiple doctor visits, daily life disruptions, contact lens discomfort, difficulty wearing makeup, and increased risk of anxiety and depression. Demodex blepharitis is common in contact lens wearers and cataract surgery patients, and it may contribute to contact lens intolerance and affect visual outcomes after surgery. It is important for clinicians to have a heightened suspicion of Demodex blepharitis in these populations and to screen preoperative patients for ocular surface and lid disease. 

At the time of being published, there were no FDA-approved treatments for Demodex blepharitis. Several options, including OTC and office-based devices, have been studied, but none have been proven effective. Other management approaches include the using ivermectin, metronidazole, tea tree oil, and in-office procedures like intense pulsed light and microblepharoexfoliation. However, more research is needed to establish their efficacy. 

A promising treatment that has finished late-stage clinical trials is Lotilaner ophthalmic solution, 0.25% (TP-03). Lotilaner is a lipophilic and an acaricide of the isoxazoline parasiticide class and a veterinary medication approved for use in several countries, including the US and EU, for treating ticks and fleas in pets. Ectoparasites exposed to isoxazolines exhibit spastic paralysis leading to their eventual starvation and death.  

Four phase 2 studies have shown that an eye drop called TP-03 effectively reduces collarettes and Demodex density and is well tolerated. The studies included a pilot study with 28 days of twice-daily dosing and 90 days of follow-up, a randomized controlled trial, and two studies with extended 6-week dosing. In the most recent pivotal phase 2b/3 trial, the TP-03 group had significantly higher rates of reduction in collarettes, collarette cure, mite eradication, and erythema cure than the control group. The trial enrolled 421 patients and a second phase 3 study confirmed these results with an additional 412 patients. Most patients found that the medication was well-tolerated, with mild ocular adverse events being the most common side effect.  

“Current options for the management of Demodex blepharitis are burdensome, inconvenient, and may be ineffective and/or toxic to ocular tissues,” said researchers. “The development of a more effective, tolerable, safe, convenient, and regulatory body–approved treatment for Demodex blepharitis would benefit patients and provide practitioners with the first targeted tool to combat this prevalent disease.”  

Reference  

Rhee MK, Yeu E, Barnett M, et al. Demodex blepharitis: a comprehensive review of the disease, current management, and emerging therapies. Eye & Contact Lens. 2023;49(8), 311–318. doi:10.1097/ICL.0000000000001003