Efficacy and Safety of Lotilaner Ophthalmic Solution (0.25%) for the Treatment of Demodex Blepharitis: A GRADE Assessed Systematic Review and Meta-Analysis of Observational & Experimental Studies.

PURPOSE: Several treatments have been in use for Demodex blepharitis, before the discovery of lotilaner, like tea tree oil and antibiotics; however, they either have irritable effects or systemic adverse effects, respectively. Lotilaner, a novel ectoparasiticide, has been proposed as a treatment for patients grappling with Demodex blepharitis. This review aims to assess the safety and efficacy of lotilaner in the treatment of Demodex blepharitis. DESIGN: Systematic review and meta-analysis. METHODS: An extensive search was conducted on PubMed, Cochrane Library, Scopus, and Google Scholar to find relevant literature till July 31, 2023 following the PRISMA guidelines. A total of 143 articles were retrieved by database searching, out of which 6 studies met the inclusion criteria and were included in the review. Four randomized controlled trials were included in the meta-analysis of mite eradication incidence. The review is registered with PROSPERO: CRD42023459997. RESULTS: Lotilaner is effective in eradicating Demodex mites in individuals suffering from Demodex blepharitis according to RR for the intervention versus the control group of 3.55 (95% confidence interval [CI]: 2.87-4.40, P < .00001, I2 = 0%). The meta-analysis of clinically meaningful collarette score revealed the summary RR for the intervention versus the control group was 3.15 (95% CI: 2.56-3.89, P < 0.00001, I2 = 27%). In conclusion, the results of the included studies were comparable and consistent. CONCLUSIONS: Our results indicated that lotilaner is an effective, well-tolerated, and promising drug in treating patients with Demodex blepharitis. Lotilaner administration and cost-effectiveness should now be contemplated for the study population as these constituents have a vital impact on its treatment success.

The effect of phototherapy on Demodex density: a case-control study.

BACKGROUND: Human Demodex mites, Demodex folliculorum and Demodex brevis, are microorganisms that reside in the pilosebaceous units, usually without causing symptoms. Phototherapy has been linked to demodicosis in previous studies. We aimed to determine whether there was an increase in the frequency of demodicosis and Demodex density after 20 phototherapy sessions. METHODS: A case-control study was conducted with 32 participants who received narrowband ultraviolet B or ultraviolet A-1 therapy for various dermatological indications. Standardized skin surface biopsies were performed before and after phototherapy to assess Demodex density. The presence of Demodex-related skin conditions was assessed before phototherapy. A statistical analysis was performed to compare the Demodex densities and prevalence of demodicosis between the baseline and 20th session of phototherapy. RESULTS: No significant change was observed in Demodex density after 20 sessions of phototherapy. The average Demodex density before treatment was 2.75 ± 4.48 (/cm2 ), and after treatment, it was 2.85 ± 4.81 (/cm2 ), indicating no significant difference (P = 0.879). The percentage of patients with demodicosis in at least one region of the face was 28.1% (9/32) before treatment, and after treatment, it was 31.3% (10/32), with no significant difference (P = 1.00). CONCLUSIONS: Our findings contradict previous studies that suggested an increased Demodex density and demodicosis prevalence after phototherapy. The data from previous studies are open to debate due to their selected samples, designs, and interpretations regarding the phototherapy-immunosuppression-Demodex relationship. Larger-scale longitudinal studies conducted on a homogeneous sample are warranted to better understand the relationship between phototherapy and demodicosis.

Natural Products as Mite Control Agents in Animals: A Review.

Mites have been a persistent infectious disease affecting both humans and animals since ancient times. In veterinary clinics, the primary approach for treating and managing mite infestations has long been the use of chemical acaricides. However, the widespread use of these chemicals has resulted in significant problems, including drug resistance, drug residues, and environmental pollution, limiting their effectiveness. To address these challenges, researchers have shifted their focus towards natural products that have shown promise both in the laboratory and real-world settings against mite infestations. Natural products have a wide variety of chemical structures and biological activities, including acaricidal properties. This article offers a comprehensive review of the acaricidal capabilities and mechanisms of action of natural products like plant extracts, natural compounds, algae, and microbial metabolites against common animal mites.

Diagnosis and treatment of filamentary keratitis in a patient with Demodex infestation--an overlooked risk factor: a case report.

BACKGROUND: Filamentary keratitis is an ocular condition that is tricky to handle for the difficulty to find the underlying cause. Here we report a case of filamentary keratitis associated with Demodex infestation which highlights the importance of Demodex mites as an easily-overlooked risk factor. CASE PRESENTATION: A 63-year-old woman had recurrent symptoms of foreign body sensation and sometimes painful feelings in her left eye soon after her surgical correction of ptosis in this eye. She was then diagnosed as conjunctivitis and given antibiotic eye drops. After one week, the patient complained of aggravation of symptoms with small corneal filaments in the left eye under slit-lamp examination. Despite the removal of filaments and addition of topical corticosteroids and bandage contact lenses, the patient's condition persisted with enlarged filaments and severe ocular discomfort. 3 days later, eyelashes with cylindrical dandruff were noticed and Demodex infestation was confirmed by microscopic examination of these eyelashes at our clinic this time. She was asked to use tea tree oil lid scrub twice daily. After 3 weeks, her filamentary keratitis was resolved with a dramatic improvement in symptoms and signs. And no recurrence of filamentary keratitis was noticed during the one-year follow-up. CONCLUSIONS: In this case, filamentary keratitis was resolved only with treatment of Demodex infestation while conventional treatment failed. Considering the fact that Demodex infestation is a common but easily overlooked condition, it may be suggestive to take Demodex infestation into account as a risk factor of filamentary keratitis, especially in refractory cases.

Role of Blepharoexfoliation in Demodex Blepharitis: A Randomized Comparative Study.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of blepharoexfoliation in the treatment of Demodex blepharitis. METHODS: Patients with microscopically approved Demodex blepharitis were enrolled. Patients in the treatment group were treated once with in-office blepharoexfoliation (BlephEx LLC; Franklin, TN) using tea tree oil 2% shampoo, followed by eyelid scrubs with tea tree oil 2% shampoo twice a day for 8 weeks. Patients in the control group were treated with the same protocol, except for the in-office sham blepharoexfoliation procedure. As the main outcome measurement, the changes in the severity of symptoms [Ocular Surface Disease Index (OSDI) score] were compared. The changes in Demodex count and meibomian gland dysfunction (MGD) severity were compared as the secondary outcome measurements. RESULTS: Eighty-one patients (36 male and 45 female) were included. The mean age of the patients was 53.56 ± 8.13 years. The mean baseline OSDI score was 33.30 ± 11.80. The mean baseline Demodex count was 4.84 ± 1.49. The Demodex count at the baseline visit was moderately correlated with the baseline OSDI score (R = 0.526, P = 0.011) and baseline MGD severity ( P = 0.02). At the 8-week visit, the OSDI score was 22.62 ± 8.23 and 27.09 ± 9.11 in the blepharoexfoliation and control groups, respectively ( P = 0.016). At the 8-week visit, the Demodex count was 2.6 ± 1.08 and 3.03 ± 1.27 in the treatment and control groups, respectively ( P = 0.025). MGD improved in both groups ( P = 0.84). In the blepharoexfoliation group, the change in the OSDI score was moderately correlated with the baseline OSDI score (R = 0.611, P = 0.01). CONCLUSIONS: One session of blepharoexfoliation, followed by manual eyelid scrubs was more effective than eyelid scrubs alone in reducing patients' symptoms and Demodex count.

Evaluation of a novel treatment, selenium disulfide, in killing Demodex folliculorum in vitro.

OBJECTIVE: To evaluate the effectiveness of varying concentrations of selenium sulfide, an active ingredient in antidandruff shampoo, in killing Demodex folliculorum. METHODS: Sixty-five eyelashes with live Demodex from 29 patients seen at the Nassau University Medical Center (17 patients) and Ophthalmic Consultants of Long Island (12 patients) were observed under light microscopy for 90 minutes in 0.1%, 0.5%, 1.0%, and 4% selenium sulfide with either carboxymethyl cellulose (CMC) solution or petroleum jelly ointment (Vaseline, Unilever, London) as excipients. Positive and negative controls also were evaluated as separate solutions of CMC, petroleum jelly, basic saline solution, 50% tea tree oil, and 100% tea tree oil. The number of Demodex deaths and time of death were recorded. RESULTS: Demodex deaths in the selenium sulfide reagents were observed in the 4% selenium sulfide solution with CMC (36.4% kill rate, 4 of 11 Demodex, average time of death 17.5 minutes, p = 0.038) and 4% selenium sulfide with petroleum jelly ointment (12.5% kill rate, 1 of 8 Demodex, time of death 75 minutes, p = 0.351). No Demodex deaths were witnessed in the other selenium sulfide treatment groups. All Demodex died in the 50% and 100% tea tree oil positive control group. CONCLUSIONS: Selenium sulfide has shown efficacy in killing Demodex at a 4% concentration with the CMC solution and mild activity with 4% petroleum jelly. More research on selenium sulfide solutions at higher concentrations is indicated.

Recent Evidence of Tea Tree Oil Effectiveness in Blepharitis Treatment.

The purpose of our study is to see how beneficial is tea tree oil (TTO) for treating chronic blepharitis topically, with a focus on the Demodex mite. To discover all possibly relevant published papers, an accurate Pubmed database search analysis of the current literature was undertaken from 2012 to December 2021. Fourteen papers dealing with the use of TTO to treat chronic blepharitis have been found. The effectiveness of TTO treatment was tested in vitro by 4 authors and in vivo by 10 authors. All studied confirmed efficacy of TTO treatment, even cyclic, on Demodex mite blepharitis. TTO can be used for lid scrubs, facial cleanser, eyelid patch, eyelid gel, eyelash shampoo or, more commonly, as TTO impregnated eyelid wipes. The scientific evidence of TTO for chronic blepharitis treatment gives a lot of confidence for the progress that this treatment may have in the future clinical practice.

Evaluation of the in vitro acaricidal activity of ethanol extracts of seven Chinese medicinal herbs on Ornithonyssus sylviarum (Acari: Macronyssidae).

Ornithonyssus sylviarum (Acari: Macronyssidae) is a common ectoparasite that feeds on the blood of poultry. Following infestation, this mite will cause symptoms such as weight loss, anemia, and decreased egg production. To explore green and safe drugs for the prevention and treatment of O. sylviarum, this study evaluated the effects of ethanol extracts of seven Chinese medicinal herbs-Leonurus artemisia (motherwort), Illicium verum (star anise), Cinnamomum cassia (cinnamon), Hibiscus syriacus, Artemisia argyi (Chinese mugwort), Taraxacum sp. (dandelion), and Syzygium aromaticum (clove)-on O. sylviarum at different life stages. The results showed that different methods of administration affected the acaricidal efficacy of these plant extracts on O. sylviarum. After 6 h of administration with the fumigation method, the acaricidal efficacy of S. aromaticum on adults, nymphs and larvae of O. sylviarum reached 100%. 30 min after administration with the infiltration method, S. aromaticum, H. syriacus and L. artemisia showed acaricidal effects on adults and nymphs of O. sylviarum reaching 100%. In another experiment evaluating the inhibition of egg hatching of O. sylviarum with alcohol extracts of these seven herbs, at 48 h after treatment, A. argyi and C. cassia showed inhibition rates of 19.4%. The results of this study indicate that S. aromaticum induced mortality at all stages of O. sylviarum, whereas A. argyi was found to be the most effective at inhibiting the mite's egg hatching among the seven herbs. These herbs can therefore be used as potential substitutes for chemical pesticides to prevent and control O. sylviarum. These results provide practical knowledge for the control of O. sylviarum.

The comparative in vitro killing activity of tea tree oil versus permethrin on Demodex folliculorum of rosacea patients.

BACKGROUND: Demodex mites have been implicated in several cutaneous disorders compelling the research efforts for effective anti-Demodex therapy. OBJECTIVE: Compare the survival time (ST) of Demodex folliculorum exposed to six different concentrations of tea tree oil (TTO) versus a positive control (permethrin 5%) and a negative control (immersion oil) group. MATERIALS AND METHODS: The wastes of rosacea patients' standardized superficial skin biopsy samples were recruited for the trial. The primary outcome measure of this study was the survival time, defined as the period between the exposure of study agents to the complete cessation of Demodex movements. RESULTS: All differences between the mean survival times of 2.5% (54.0 ± 6.1), 5% (39.0 ± 3.9), 10% (22.0 ± 2.5), 25% (13.0 ± 2.5), 50% (7.8 ± 0.6), and 100% TTO (3.3 ± 1.3) were significant (p < 0.05). The ST of the negative control group was 196.0 ± 23.6 min. The ST of permethrin 5% was 12.5 ± 1.9 that did not show a statistically significant difference from the ST of TTO 25% (p = 0.628). CONCLUSION: The survival times of the six different TTO groups confirmed a dose-related pattern, all of which had survival times shorter than the negative control (immersion oil). TTO 25% had comparable efficacy to the positive control agent (permethrin 5%).

Update on the Management of Demodex Blepharitis.

ABSTRACT: Demodex blepharitis is a common ophthalmologic disease that is often overlooked in the workup of blepharitis. Demodex infestation occurs in both symptomatic and asymptomatic individuals at similar rates; consequently, its role in the development of blepharitis has not been well elucidated. Two species have been confirmed to inhabit the human eyelid- Demodex folliculorum and Demodex brevis. These species differ in their preferred location of infestation, with D. folliculorum occupying the base of the eyelash and D. brevis inhabiting the meibomian glands, contributing to anterior and posterior Demodex blepharitis, respectively. A clinical index of suspicion must be developed from the history when blepharitis, conjunctivitis, or keratitis in adults and blepharoconjunctivitis or chalazia in children are resistant to treatment. The diagnosis can be strongly suspected by the presence of cylindrical dandruff at the base of the eyelash and confirmed by light microscopy of an epilated lash or by in vivo confocal microscopy. No cure is currently available. Management most frequently includes topical tea tree oil and its active ingredient terpinen-4-ol, both of which have produced good clinical outcomes. Topical tea tree oil is typically applied by a professional due to risk of toxicity. Several second-line treatment options have been studied, including ivermectin, metronidazole, selenium sulfide, microblepharoexfoliation, and lid hygiene. Novel, targeted therapies such as TP-03 (Tarsus Pharmaceuticals) are also currently being investigated in phase 2b/3 clinical trials. The purpose of this review purpose is to characterize Demodex blepharitis in detail, including its historical perspective and various classifications, and describe the latest diagnostic and management strategies.

Different Approach to Manage Demodex Blepharitis - Initial and Maintenance Treatment.

PURPOSE/AIM OF THE STUDY: To evaluate the improvement of ocular signs and symptoms in patients suffering from Demodex blepharitis using a combined treatment approach: use of eyelid wipes impregnated with 2.5% terpinen-4-ol (T4O) and 0.2% hyaluronic acid (HA) in the initial treatment period and investigation of maintenance of the treatment effect with the use of eyelid cleansing wipes. MATERIALS AND METHODS: Fifty patients with Demodex blepharitis were treated in the initial treatment period with sterile eyelid T4O impregnated wipes for 28 days. In the following four-week maintenance period, 82% patients received sterile eyelid maintenance wipes, while 16% continued treatment with T4O impregnated wipes. Global ocular discomfort, adapted TOSS, SANDE score, and individual blepharitis symptoms were assessed by patients at day 28 and day 56. Ocular signs were evaluated by the investigator at the study visits. Investigator's assessment of the overall treatment performance, patient's assessment of treatment satisfaction, and tolerability were evaluated with questionnaires. RESULTS: All global ocular discomfort symptoms and disease specific symptoms assessed by patients as well as all parameters evaluated by the investigators significantly improved in the initial treatment period with the application of eyelid wipes impregnated with 2.5% terpinen-4-ol until day 28. The therapeutic effect was maintained or even improved during the maintenance period under administration of mainly eyelid maintenance wipes until day 56. Both products were well tolerated. No adverse events and no clinically relevant changes in visual acuity were observed during both periods. CONCLUSIONS: Once daily treatment with T4O impregnated eyelid wipes in the initial treatment period significantly improved the ocular symptoms and signs and reduced the mite count in patients with Demodex blepharitis within four-weeks administration. Subsequent maintenance treatment with maintenance wipes for another 4 weeks preserved or further intensified the treatment success. The products were well tolerated and were convenient to use.

Swabs Containing Tea Tree Oil and Chamomile Oil Versus Baby Shampoo in Patients With Seborrheic Blepharitis: A Double-Blind Randomized Clinical Trial.

PURPOSE: The comparison of the efficacy of swabs containing tea tree oil and chamomile oil and baby shampoo (BS) in the treatment of seborrheic blepharitis was aimed. METHODS: This randomized, double-blind, parallel-group, active control, multicenter clinical trial included patients with seborrheic blepharitis using block randomization (BS, n=23; swabs, n=26). Patients were treated with BS or swabs for 8 weeks followed by 4 weeks of treatment withdrawal. Change in Blepharitis Symptom measure (BLISS), Demodex count, Ocular Surface Disease Index (OSDI) score, Schirmer test, tear breakup time (TBUT), noninvasive TBUT (NI-TBUT), corneal staining, and meibography at different visits (baseline, fourth, , and 12th week) were the main outcome measures. RESULTS: Patients in both groups showed similar baseline parameters (P>0.05). Patients using swabs showed significantly lower BLISS scores compared with patients using BS at the 4th, 8th, and 12th week visits (3.6±6.1 vs. 6.3±4.5 P=0.011; 1.1±2.8 vs. 6.6±6.7, P<0.001; 0.9±2.8 vs. 5.7±6.6, P=0.002, respectively). Patients using swabs showed improvement in OSDI scores after 8 weeks of treatment compared with the baseline visit (P<0.001). Despite a similar Demodex reduction effect in both treatment arms even after 4 weeks of treatment (P<0.001), both treatment modalities did not show any effect on the other parameters. CONCLUSION: Although both swabs and BS showed efficacy for the treatment of seborrheic blepharitis in terms of the Demodex reduction and symptomatic improvement, swabs may provide better symptomatic improvement. Four weeks of treatment discontinuation may not cause any recurrence in the symptoms or Demodex infestation.

Corneal Effects of Tea Tree Oil.

PURPOSE: The purpose of this study is to report a case of corneal epithelial defects resulting from topical treatment of blepharitis with tea tree oil (TTO). METHODS: A 44-year-old man with a 1 year history of blepharitis non-responsive to eyelid hygiene was found to have signs of Demodex infestation. He was treated with a topical, off-label 50% TTO solution. Shortly afterward, the patient complained of bilateral ocular discomfort. RESULTS: Slit-lamp examination revealed conjunctival injection and a corneal epithelial defect in both eyes. Treatment with lubricant, antibiotic, and steroid eye drops as well as bandage contact lenses was required to facilitate corneal healing. CONCLUSIONS: Topical use of off-label, 50% concentration TTO can result in corneal epithelial defects. Eye care professionals should remain aware of this risk and only use approved, low-concentration TTO products when treating Demodex-related blepharitis.

Plant-based supplement containing B-complex vitamins can improve bee health and increase colony performance.

It is common knowledge that nutritive stress resulting from decreased diversity and quality of food, pollution of food sources and beekeeping errors may lead to increased susceptibility of bees to pathogens and pesticides. The dearth of adequate food is frequently compensated with supplements. Thus, this research was aimed to study the effects of the plant-based supplement B + on colony strength (assessed according to open and sealed brood area, honey and pollen/bee bread reserves, and the number of adult bees). In addition, Nosema ceranae spores and viruses were quantified and the level of infestation with Varroa destructor assessed. The experiment was conducted in late summer and early spring. In colonies which were given B + in feed a significant increase (p < 0.05) in the parameters of colony strength were noticed in comparison to the control (colonies fed on sugar syrup). Moreover, it was proven that the bees from these colonies had significantly lower (p < 0.05) N. ceranae spore counts, and acute bee paralysis, deformed wing and sacbrood virus loads. Our results suggest that the addition of B + supplement to the colonies provide them with nutrients, contribute to their strengthening, might prevent nutritive stress and increase the success of bees in combating pathogens.

The Effect of Volatile Oil from Chinese Mugwort Leaf on Human Demodecid Mites In Vitro.

BACKGROUND: Human demodecid mites including Demodex folliculorum and Demodex brevis Akbulatova can cause acne, rosacea, epifolliculitis, blepharitis, seborrheic dermatitis, perioral dermatitis, acromastitis and such skin health problems. Artemisia (Composiate) are widely distributed in temperate regions in the northern hemisphere. It has been reported that 17 species of plants in Artemisia used to be mugwort in China. Mugwort volatile oil (MVO) has antibacterial and antiviral effects, can relieve cough and asthma, acts as an expectorant, choleretic and sedative, and promotes circulation and enhances immunity. PURPOSE: This research was to observe the effect of MVO on two types of human demodecid mites in vitro. METHODS: The MVO was obtained via the supercritical CO2 extraction method, and the human demodecid mites were acquired with cellophane tape. MVO had a distinct killing effect on two types of human demodecid mites, Demodex folliculorum and Demodex brevis. The body of the demodecid mites has a classical temporal process, which consists of excitement, contractions, death and transparency. The killing time was lengthened with decreasing concentration, thus showing an evident dependence on concentration. RESULTS: The experiment showed that 3.125% was the minimum effective concentration of MVO for killing D. brevis, and 6.25% was the minimum effective concentration for killing D. folliculorum; the killing effect of MVO on D. brevis was greater than on D. follilorum. CONCLUSION: This result suggests that mugwort, which acts as a traditional Chinese herbal medicine, has a noticeable killing effect on human demodecid mites.

Efficacy of cyclic therapy with terpinen-4-ol in Demodex blepharitis : Is treatment possible by considering Demodex's life cycle?

PURPOSE: To describe the effectiveness of cyclic treatment with terpinen-4-ol, a tea tree oil component, on Demodex blepharitis. METHODS: The presence of Demodex was determined by eyelash rotation as proposed by Mastrota. Schirmer test, tear breakup time, ocular surface disease index, lid margin score, meibomian gland expressibility score, and Oxford grade were performed. Patients were advised to apply heat followed by terpinen-4-ol soaked wipes to eyelids twice a day for 2 weeks. At the end of 2 weeks, treatment was interrupted for 7-10 days. The same treatment was repeated once again. The patients were examined after the first and second cycle of treatment and after 1 year. RESULTS: There was a statistically significant improvement in Schirmer test (10.37 ± 4.73 and 13.13 ± 3.44 mm/5 min), tear breakup time (6.47 ± 3.31 and 7.6 ± 2.89 s), ocular surface disease index (47.94 ± 19.77 and 34.28 ± 13.40), lid margin score (3.2 ± 0.7 and 2.63 ± 0.71), meibomian gland expressibility scores (1.93 ± 0.64 and 1.4 ± 0.67), and Oxford grade (0.9 ± 0.8 and 0.5 ± 0.63) after the first cycle of treatment (p < 0.05). The improvement in symptoms and tear function tests of the patients after the second cycle was significantly better than in pre-treatment levels. At 12-month follow-up, symptoms of two patients (93%) relapsed. CONCLUSION: The administration of terpinen-4-ol to the eyelid margins in a cyclic manner in Demodex blepharitis is effective against adult and hatching Demodex and breaks the vicious cycle.

Comparison of the efficacy of tea tree (Melaleuca alternifolia) oil with other current pharmacological management in human demodicosis: A Systematic Review.

Various treatments are found to be moderately effective in managing Demodex-related diseases except tea tree oil (TTO) and terpinen-4-ol (T4O), which showed superior miticidal and anti-inflammatory effects in numerous clinical studies. Their possible effects include lowering mite counts, relieving Demodex-related symptoms, and modulating the immune system. This review summarizes the current clinical topical and oral treatments in human demodicosis, their possible mechanisms of action, side-effects and resistance in treating this condition. TTO (especially T4O) is found to be the most effective followed by metronidazole, ivermectin and permethrin in managing the disease. This is because TTO has anti-parasitic, anti-bacterial, anti-fungal, anti-inflammatory and wound-healing effects. Furthermore, nanoTTO can even release its contents into fungus and Pseudomonas biofilms. Combinations of different treatments are occasionally needed for refractory cases, especially for individuals with underlying genetic predisposal or are immuno-compromised. Although the current treatments show efficacy in controlling the Demodex mite population and the related symptoms, further research needs to be focused on the efficacy and drug delivery technology in order to develop alternative treatments with better side-effects profiles, less toxicity, lower risk of resistance and are more cost-effective.

Tea tree oil for Demodex blepharitis.

BACKGROUND: Demodex blepharitis is a chronic condition commonly associated with recalcitrant dry eye symptoms though many people with Demodex mites are asymptomatic. The primary cause of this condition in humans is two types of Demodex mites: Demodex folliculorum and Demodex brevis. There are varying reports of the prevalence of Demodex blepharitis among adults, and it affects both men and women equally. While Demodex mites are commonly treated with tea tree oil, the effectiveness of tea tree oil for treating Demodex blepharitis is not well documented. OBJECTIVES: To evaluate the effects of tea tree oil on ocular Demodex infestation in people with Demodex blepharitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 6); Ovid MEDLINE; Embase.com; PubMed; LILACS; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We used no date or language restrictions in the electronic search for trials. We last searched the databases on 18 June 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared treatment with tea tree oil (or its components) versus another treatment or no treatment for people with Demodex blepharitis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts and then full text of records to determine their eligibility. The review authors independently extracted data and assessed risk of bias using Covidence. A third review author resolved any conflicts at all stages. MAIN RESULTS: We included six RCTs (1124 eyes of 562 participants; 17 to 281 participants per study) from the US, Korea, China, Australia, Ireland, and Turkey. The RCTs compared some formulation of tea tree oil to another treatment or no treatment. Included participants were both men and women, ranging from 39 to 55 years of age. All RCTs were assessed at unclear or high risk of bias in one or more domains. We also identified two RCTs that are ongoing or awaiting publications. Data from three RCTs that reported a short-term mean change in the number of Demodex mites per eight eyelashes contributed to a meta-analysis. We are uncertain about the mean reduction for the groups that received the tea tree oil intervention (mean difference [MD] 0.70, 95% confidence interval [CI] 0.24 to 1.16) at four to six weeks as compared to other interventions. Only one RCT reported data for long-term changes, which found that the group that received intense pulse light as the treatment had complete eradication of Demodex mites at three months. We graded the certainty of the evidence for this outcome as very low. Three RCTs reported no evidence of a difference for participant reported symptoms measured on the Ocular Surface Disease Index (OSDI) between the tea tree oil group and the group receiving other forms of intervention. Mean differences in these studies ranged from -10.54 (95% CI - 24.19, 3.11) to 3.40 (95% CI -0.70 7.50). We did not conduct a meta-analysis for this outcome given substantial statistical heterogeneity and graded the certainty of the evidence as low. One RCT provided information concerning visual acuity but did not provide sufficient data for between-group comparisons. The authors noted that mean habitual LogMAR visual acuity for all study participants improved post-treatment (mean LogMAR 1.16, standard deviation 0.26 at 4 weeks). We graded the certainty of evidence for this outcome as low. No RCTs provided data on mean change in number of cylindrical dandruff or the proportion of participants experiencing conjunctival injection or experiencing meibomian gland dysfunction. Three RCTs provided information on adverse events. One reported no adverse events. The other two described a total of six participants randomized to treatment with tea tree oil who experienced ocular irritation or discomfort that resolved with re-educating the patient on application techniques and continuing use of the tea tree oil. We graded the certainty of the evidence for this outcome as very low. AUTHORS' CONCLUSIONS: The current review suggests that there is uncertainty related to the effectiveness of 5% to 50% tea tree oil for the short-term treatment of Demodex blepharitis; however, if used, lower concentrations may be preferable in the eye care arena to avoid induced ocular irritation. Future studies should be better controlled, assess outcomes at long term (e.g. 10 to 12 weeks or beyond), account for patient compliance, and study the effects of different tea tree oil concentrations.

Review of extralabel use of isoxazolines for treatment of demodicosis in dogs and cats.

Amitraz is presently the only FDA-approved treatment for demodicosis in dogs in the United States. Amitraz treatment involves a protracted course of administration and risks of severe adverse effects such as sedation, bradycardia, and respiratory depression, which are caused by activation of α2-adrenergic receptors. Other treatment options include macrocyclic lactones and lime sulfur, but these products have varied efficacy and high risks of adverse effects. Several recent studies have indicated that isoxazolines are capable of reducing Demodex mite counts in canine and feline patients with demodicosis by ≥ 99% in as little as 1 month with few adverse effects. This article reviews the status of isoxazolines in regard to labeled uses in dogs and cats in the United States, extralabel clinical use for treatment of demodicosis in these species, and safety of orally administered formulations of these drugs.

Diagnosis and treatment of demodicosis in dogs and cats: Clinical consensus guidelines of the World Association for Veterinary Dermatology.

BACKGROUND: Demodicosis is a common disease in small animal veterinary practice worldwide with a variety of diagnostic and therapeutic options. OBJECTIVES: To provide consensus recommendations on the diagnosis, prevention and treatment of demodicosis in dogs and cats. METHODS AND MATERIALS: The authors served as a Guideline Panel (GP) and reviewed the literature available before December 2018. The GP prepared a detailed literature review and made recommendations on selected topics. A draft of the document was presented at the North American Veterinary Dermatology Forum in Maui, HI, USA (May 2018) and at the European Veterinary Dermatology Congress in Dubrovnik, Croatia (September 2018) and was made available via the World Wide Web to the member organizations of the World Association for Veterinary Dermatology for a period of three months. Comments were solicited and responses were incorporated into the final document. CONCLUSIONS: In young dogs with generalized demodicosis, genetic and immunological factors seem to play a role in the pathogenesis and affected dogs should not be bred. In old dogs and cats, underlying immunosuppressive conditions contributing to demodicosis should be explored. Deep skin scrapings are the diagnostic gold standard for demodicosis, but trichograms and tape squeeze preparations may also be useful under certain circumstances. Amitraz, macrocyclic lactones and more recently isoxazolines have all demonstrated good efficacy in the treatment of canine demodicosis. Therapeutic selection should be guided by local drug legislation, drug availability and individual case parameters. Evidence for successful treatment of feline demodicosis is strongest for lime sulfur dips and amitraz baths.