Over the past decade, eyecare providers have been increasingly drawn to the presence of Demodex mites on the eyelid and lash follicles as potential contributors to a string of ocular health issues – from chronic styes to blepharitis to ocular rosacea. Current standard of care for eradicating Demodex associated blepharitis is treatment with 50% tea tree oil-based eyelid cleanser and 5% tea tree oil ointment for up to 4 weeks. “But there are almost no clinical studies looking at the impact of these treatments on the eye,” Dr. David Sullivan explains during this podcast.
Dr. David Sullivan, founder of the Tear Film and Ocular Surface Society and current Chairman of the Board of Directors, is a PhD whose lab at Schepens Eye Research Institute/Harvard Medical School has brought forward many new insights into ocular surface disease treatment and management over the last 40 years. Working as a fellow in his lab, Di Chen, MD, PhD, had the idea to investigate what tea tree oil was doing to meibomian gland cells if we knew from prior research that tea tree oil had endocrine disruptive hormonal effects on human cells. “We wanted to test if tea tree oil would have the same effect on meibomian gland cells because we know that a lot of doctors use tea tree oil products on eyelids, and we don’t know its’ effects,” Dr. Chen explains about the inspiration behind her research. “We know [tea tree oil] can kill Demodex, but we don’t know it’s effects on human cells so why don’t we test this on human meibomian gland cells. To our surprise it killed those cells.”
Her new study demonstrates that tea tree oil at the concentrations currently used in commercially available eyelid cleansers (and even considerably lower strengths) will not only kill Demodex populations, but the healthy meibomian gland ocular tissue we are trying to preserve.
Terpinen-4-ol (T4O) is the active ingredient in tea tree oil that is most effective in killing Demodex; in vitro studies show that exposure to 1% T4O for 88 minutes or 4% T4O for 44 minutes can kill Demodex mites. In routine use today are eyelid cleansing wipes containing between 2-4% T4O for eyelid hygiene or even makeup removal. In this study, researchers tested cultured human meibomian gland epithelial cells in vitro with exposure to dose and time dependent concentrations of T4O. After just 15 minutes of exposure to 1% T4O, human meibomian gland epithelial cells exhibited cell morphology changes and atrophy, and after 90 minutes of such treatment, all cells died. At the same concentration and exposure time that it takes to kill Demodex mites, the human meibomian gland cells we are trying to “treat” with tea tree oil-based lid hygiene prescribed for posterior blepharitis or chronic styes or chalazion are also killed.
There has been very little literature published on the effects of tea tree oil and T4O on the health of the ocular surface tissues being exposed during treatment. We do know that T4O is a small molecule that can rapidly penetrate through the skin epidermal tissue. Prior studies have demonstrated that after application of 2-4% tea tree oil ointment to the skin, tea tree oil components permeate the tissue and remain at concentrations of 0.23 – 0.37% after 24 hours. Extrapolated to eyelid skin, a concentration of 0.2% T4O for 24 hours would kill human meibomian gland cells based on the results of this study.
The toxicity of tea tree oil in human tissue has been documented and well reported outside of eyecare specific applications. Multiple studies cite tea tree oil and T4O as toxic to human hepatic, cervical, breast epithelial, and bone marrow cells in vitro. Additionally, they have been cited as endocrine disruptors, expressing both estrogen and anti-androgen effects. The European Cosmetic Toiletry and Perfumery Association in 2002 published the following recommendation: “TTO should not be used in cosmetic products in a way that results in a concentration greater than 1% oil being applied to the body.”
“What are people doing?” Dr. David Sullivan encourages doctors to ask. “There are a lot of companies making these tea tree oil products, but we need to know more about what they are doing in vivo to humans. Caution needs to be exercised in repeatedly giving these things to patients.” More research is needed to understand the risks of repeated tea tree oil exposure to the health of the ocular surface tissue. Eyecare providers should be aware of these potential risks and caution patients against the use of tea tree oil based ocular cleansing products for routine use. Dr. Sullivan outlines several alternatives available to practitioners that have shown to be effective against Demodex including microblepharoexfoliation, Intense Pulsed Light (IPL), and Manuka honey.
“In daily practice we need to balance the benefits versus risks,” explains Dr. Chen. “It may kill the Demodex but we need to pick the appropriate patients. Not all patients with Demodex should get tea tree oil treatment. Some patients will feel much better with tea tree oil treatments, but not every patient with blepharitis should be using tea tree oil. There may be more harm than benefits in those cases.”
In addition to a lack of research on the safety of tea tree oil-based products, there is also a fundamental lack of research on how important treating Demodex is for patients with chronic meibomian gland dysfunction. Demodex mites are extremely common, with 84% of humans age 60 and older and 100% of humans age 70 and older being found to have Demodex present on their eyelid skin. Studies have found association with the presence of demodex with a variety of ocular health issues, but the clinical significance of Demodex infestation remains debatable because it is also found in asymptomatic patients. “Why are we killing those little bugs?” Dr. Sullivan encourages doctors to ask. “What do they do? What is the evidence that they cause meibomian gland dysfunction? There’s almost a complete lack of data as to whether Demodex have any effect on the meibomian gland. Think of the microbiome as well. Bacteria help you. Is it really important to get rid of them?”
Dr. Di Chen sums it up nicely: “We have to be more responsible for the decisions we make and put the patient’s interest first by balancing the benefits versus harms of any products we prescribe or recommend.”