In July 2023, the FDA approved the first pharmaceutical treatment for Demodex blepharitis, irritation of the eyelids caused by face mites. This groundbreaking development has generated interest in the industry, and we explore the issue further here.
The mere mention of a mite infestation is enough to give most people the ick—and those that cause Demodex blepharitis are no different. Good news, then, for those with mites on their mind (or their eyelids). In July of this year, the FDA approved XDEMVY (lotilaner ophthalmic solution 0.25%; Tarsus Pharmaceuticals, United States), the first medication that treats Demodex blepharitis at the source.
Meet the mighty mites
Demodex is a genus of modified arachnids that live as ectoparasites. Two types are specific to humans: folliculorum and brevis—better known as the face mites. Though we’re not born with them, nearly all people who live beyond middle age will eventually acquire face mites through close contact with others.
Most folks become a bit squeamish upon learning that their faces are host to a breeding population of baby (sort of) spiders. But the truth is these mites have been our lifelong companions. In fact, they are so common that, like lice, Demodex have been used by anthropologists to chart past human demographic changes. Unlike their pesty cousins, however, the nigh-microscopic Demodex enjoy a commensal relationship with humans. They live brief lives, quietly consuming our natural oils and dead skin cells—they don’t drink our blood or poison us.
So long as the immune system keeps their numbers in check, mites cause little bother. Among the elderly and immunocompromised, however, Demodex populations have a way of becoming unruly. Mites are believed to be responsible for or an aggravating factor in 60% or more of blepharitis cases in these groups.1
Demodex involvement is most easily diagnosed from the presence of tell-tale collarettes (cylindrical plugs made of mite eggs and waste products) around the base of the lashes. Demodex folliculorum, which preferentially infests the eyelashes, is particularly known for leaving behind these little calling cards. In addition to severe itching in the anterior lid, folliculorum infestation causes follicle distention and misdirected lashes. Demodex brevis, meanwhile, is known for afflicting the posterior eyelid. Burrowing into the meibomian glands, brevis mites can disrupt oil secretion, resulting in watery tears and dry eye.
The lowdown on XDEMVY
To the relief of blepharitis sufferers, Tarsus Pharmaceuticals announced FDA approval of XDEMVY (formerly known as TP-03) early this year. An eye drop delivered twice daily for a period of six weeks, XDEMVY contains lotilaner, which kills Demodex mites by inhibiting the action of GABA neurotransmitters.
To get a better sense of XDEMVY’s significance, we reached out to Dr. Elizabeth Yeu, president of the American Society of Cataract and Refractive Surgery (ASCRS).
“XDEMVY is one of the most specific isoxazolines for ectoparasites,” she said, commenting on the drug’s formulation and mechanism of action. “Exposure results in paralysis and death of the Demodex mite. Lotilaner is also highly lipophilic, making it well-suited to reach the oily lash follicles where mites reside.”
During a double-blind study, XDEMVY patients showed a reduction of collarette density and blepharitis symptoms in as little as two weeks. In some cases, complete eradication was achieved. Notable side effects included stinging at the administration site (10% of patients) and chalazia (2%).2
Dr. Yeu added, “A majority of patients do find this drop to be very comfortable to neutral. The blur that is experienced is no more than that of a large clear tear that lasts seconds.”
Tea tree oil: More harm than good?
A repeated selling point in XDEMVY literature and endorsements is that the new treatment is the first FDAapproved medicine for Demodex blepharitis. Though true, this claim might be misconstrued to suggest that no effective countermeasure existed before XDEMVY hit the market.
“Various OTC products and inoffice procedures have been used with variable efficacy for Demodex blepharitis. Tea tree oil and its derivatives (including terpinen 4-ol or T4O) have demonstrated acaricidal properties, although the exact mechanism of action against Demodex viability has not been identified,” Dr. Yeu explained.
Leading theories regarding tea tree oil’s mite-smiting properties generally focus on the active compounds terpinen-4-ol and 1,8-cineole, which are said to kill mites by disrupting cell membranes. Tea tree oil is also believed to be an irritant, causing mites to migrate out of pores and crevices for easier removal. Finally, tea tree oil also has anti-inflammatory and antibacterial properties, which can help to reduce blepharitis symptoms.3
There are many commercially available treatments for blepharitis that include tea tree oil, such as I-Lid’n Lash PRO from I-med Pharmaceuticals Canada and Oust Demodex Swabstix from Ocusoft (USA). As patients may require a topical anesthetic before treatment, these products are typically available for in-office use only. A popular home-use remedy, however, is Cliradex,
produced by Biotissue (USA), one of the only OTC offerings to include terpinen-4-ol.4
Among other drawbacks, tea tree oil is toxic if ingested and can cause allergic reactions as a topical agent. On the ocular surface, it can cause irritation and tissue damage.
To underscore this point, Dr. Yeu cited data from a recent study on tea tree oil. “Recently, an in vitro study found that even very low 0.1% and 0.01% concentrations of T4O are toxic to human meibomian gland epithelial cells,”5 she shared.
Both XDEMVY and tea tree oil products address the root cause of Demodex blepharitis—they kill face mites. Unlike XDEMVY, tea tree oil may also offer immediate symptom relief. As an herbal remedy, tea tree oil may also appeal to consumers who are leery of traditional pharmaceuticals (like arachnid neurotoxins). However, compared with XDEMVY drops, tea tree oil topicals are difficult to apply, and the consequences of misuse are greater than any currently known side effects of Tarsus’ new drug.
Dr. Yeu is cautiously optimistic about the new drug. “In my own clinical practice, I treat asymptomatic patients very frequently, particularly because I have a highly refractive surgical practice. I am using XDEMVY pre-operatively when I see at least about 1/5 to 1/4 of the upper lash cuffed with collarettes, the pathognomonic sign for collarettes, and other signs. While only time will tell, it is very encouraging to know that the long-term data does demonstrate that the Demodex blepharitis-mitigating effects are quite durable with XDEMVY,” she concluded.
- 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.
- Tarsus Pharmaceuticals Press Release. Available at: https://ir.tarsusrx.com/newsreleases/news-release-details/fda-approvesxdemvytm-lotilaner-ophthalmic-solution-025 Accessed on 27 October 2023
- Shah PP, Sten RL, Perry HD. Update on the Management of Demodex Blepharitis. Cornea. 2022;41(8):934-939.
- Contact Lens Update. Available at: https://contactlensupdate.com/2015/12/07/everything-you-wanted-to-know-and-wereafraid-to-ask-about-demodex/ Accessed on 27 October 2023
- Chen D, Wang J, Sullivan DA, et al. Effects of Terpinen-4-ol on Meibomian Gland Epithelial Cells In Vitro. Cornea. 2020;39(12):1541-1546.
Editor’s Note: A version of this article was first published in CAKE Magazine Issue 20.