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.

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.

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.

The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis.

Purpose: To investigate and compare the effect of warm compresses on meibomian gland dysfunction and Demodex folliculorum blepharitis.Methods: Forty-two subjects (13 males, 29 females; mean age of 56.45 years) enrolled and completed the two-month warm compress treatment study. Three warm compress therapies were compared: Warm face cloth, MGDRx EyeBag® and OPTASETM Moist Heat Mask. Subjects attended for four visits: baseline, two weeks, four weeks, and eight weeks. Subjective symptoms, osmolarity, non-invasive tear break-up time, ocular surface staining, Schirmer I test, meibum expressibility and clarity, and eyelash manipulation and epilation to assess for the presence of Demodex folliculorum, were measured at each visit.Results: Meibomian gland dysfunction, based on a composite score of meibum quality and expressibility, reduced significantly with the MGDRx EyeBag® and the OPTASETM Moist Heat Mask (p < .05). There was no significant difference in efficacy for treating meibomian gland dysfunction between the two devices (p = .29). No improvement in meibomian gland dysfunction was detected with the warm face cloth. Only the OPTASETM Moist Heat Mask significantly reduced the quantity of Demodex folliculorum over eight-weeks of treatment (p = .036, only baseline to week eight significant p = .008). Symptoms and ocular surface staining improved significantly in all three groups (p < .05). There was no significant change observed in osmolarity, non-invasive tear break-up time or Schirmer I test within each group (p > .05, respectively).Conclusion: The MGDRx EyeBag® and the OPTASETM Moist Heat Mask exhibited superior efficacy in treating signs and symptoms of meibomian gland dysfunction, compared to the use of a warm face cloth, over the eight-week period. The OPTASETM Moist Heat Mask demonstrated dual therapeutic abilities, treating both meibomian gland dysfunction and Demodex folliculorum blepharitis. Repeated application of heat for the treatment of meibomian gland dysfunction may continue to present a good home-remedy option for patients.

Intense Pulsed Light Therapy for Patients with Meibomian Gland Dysfunction and Ocular Demodex Infestation.

To observe the clinical changes of meibomian gland dysfunctipn (MGD) and ocular Demodex infestation after intense pulsed light (IPL) treatment to further examine the mechanism of IPL treating patients with MGD and ocular Demodex infestation. The medical records of 25 patients (49 eyes) with MGD treated with IPL, were retrospectively examined to determine outcomes. Associated ocular-surface parameters (ocular surface disease index, OSDI; lipid layer thickness, LLT; noninvasive first breakup time, NIF-BUT; noninvasive average breakup time, NIAvg-BUT; tear film breakup area, TBUA; Schirmer I Test, SIT; corneal fluorescein staining, CFS), eyelid margin abnormalities, meibum quality and expressibility, MG morphological parameters (macrostructure and microstructure), and the number of Demodex infestation were examined before and after treatment. The MG microstructure and the Demodex infestation were examined via in vivo confocal microscopy (IVCM). The results showed that there were statistically significant differences in associated ocular-surface parameters (all P<0.05) before and after IPL treatment, except SIT (P=0.065). Eyelid margin abnormalities, meibum quality and expressibility obviously improved in upper and lower eyelid after IPL treatment (all P<0.0001). MG macrostructure (MG dropouts) decreased in upper (P=0.002) and lower eyelid (P=0.001) after IPL treatment. The nine parameters of MG microstructure in upper and lower eyelid all distinctly improved after IPL treatment (all P<0.0001). The mean number of Demodex mites on the upper lid margin (6.59±7.16 to 3.12±3.81/9 eyelashes) and lower lid margin (2.55±2.11 to 1.29±1.53/9 eyelashes) significantly reduced after IPL treatment (all P<0.0001). The Demodex eradication rate was 20% (8/40) in upper lid margin and 34.15% (14/41) in lower lid margin. These findings indicate that IPL shows great therapeutic potential for patients of MGD and ocular Demodex infestation.

Efficacy of treatments for Demodex blepharitis: A systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to evaluate the efficacy of different treatment for Demodex blepharitis. Parameters studied were mites count, improvement of symptoms and mites' eradication, stratified on type of treatments and mode of delivery of treatments (local or systemic). METHOD: The PubMed, Cochrane Library, Embase, ClinicalTrials.gov, Google scholar and Science Direct databases were searched for studies reporting an efficacy of treatments for Demodex blepharitis. RESULTS: We included 19 studies (14 observational and 5 randomized clinical trials), for a total of 934 patients, 1741 eyes, and 13 different treatments. For mites count, eradication rate, and symptoms improvement, meta-analysis included fifteen, fourteen and thirteen studies, respectively. The overall effect sizes for efficiency of all treatments, globally, were 1.68 (95CI 1.25 to 2.12), 0.45 (0.26-0.64), and 0.76 (0.59-0.90), respectively. Except usual lid hygiene for mites count, Children's Hospital of Eastern Ontario ointment (CHEO) for both eradication rate and symptoms, and CHEO, 2% metronidazole ointment, and systemic metronidazole for eradication rate, all treatments were efficient. Stratified meta-analysis did not show significant differences between local and systemic treatments (1.22, 0.83 to 1.60 vs 2.24, 1.30 to 3.18 for mites count; 0.37, 0.21 to 0.54 vs 0.56, 0.06 to 0.99 for eradication rate; and 0.77, 0.58 to 0.92 vs 0.67, 0.25 to 0.98 for symptoms improvement). CONCLUSION: We reported the efficiency of the different treatments of Demodex blepharitis. Because of less systemic side effects, local treatments seem promising molecules in the treatment of Demodex blepharitis.

Therapeutic Effect of Intense Pulsed Light on Ocular Demodicosis.

PURPOSE: To evaluate the clinical efficacy of Lumenis® M22TM intense pulsed light (IPL) in reduction of ocular Demodex infestation in eyelashes in a prospective study. METHODS: Forty patients with ocular demodicosis were recruited. Then half were randomly picked to receive the IPL treatment, while the other half got 5% tea tree oil (as the control group). Demodex counts, the ocular surface disease index (OSDI) score, lid margin abnormalities, conjunctival congestion, tear break-up time (TBUT), corneal staining with fluorescein, meibomian gland (MG) expressibility, meibum quality, modified Schirmer I test with anaesthetic (SIT), were assessed on the day before treatment and after treatment of 30 and 90 days, respectively. Changes in the parameters were compared between the IPL group and the control group on the days after treatment of 30 and 90 days. RESULTS: No differences were observed in Demodex counts, lid margin abnormalities, conjunctival congestion, corneal staining with fluorescein, MG expressibility, SIT in the two groups on the days after treatment of 30 and 90 days (p > 0.05), whereas there was a statistically significant difference in the OSDI score, TBUT, meibum quality (p < 0.05). The Demodex eradication rate was more thorough in the IPL group (100%) than in the control group (75%). CONCLUSIONS: IPL shows the preferably therapeutic potential for ocular Demodicosis.

Evaluation of the Efficacy of Tea Tree Oil On the Density of Demodex Mites (Acari: Demodicidae) and Ocular Symptoms In Patients With Demodectic Blepharitis.

The objective of this study was to examine the efficacy of 7.5% tea tree oil (TTO) eyelash shampoo on the density of Demodex (Acari: Demodicidae) and ocular symptoms in patients with demodectic blepharitis. A total of 135 patients diagnosed with demodectic blepharitis, following clinical inspection and parasitological examinations, were included in the study. Patients were treated with eyelash shampoo, with or without TTO. Full Demodex reduction was attained in 36% of the patients who used eyelash shampoo with TTO, and the average Demodex count was reduced from 6.33/eyelash to zero ( P < 0.001). In contrast, the average Demodex count in patients who did not achieve full reduction (64%) was reduced from 12.46/eyelash to 4.15/eyelash ( P < 0.001). Full reduction was observed in 11.7% of patients who used TTO-free eyelash shampoo, and average Demodex count reduced from 2.00/eyelash to zero ( P = 0.017). The average Demodex count was reduced from 11.98/eyelash to 7.91/eyelash in patients (88.3%) who did not achieve full reduction ( P = 0.024). Additionally, ocular symptom scores (which are generated based on subjective experiences of itching, burning, the feeling of a foreign body in the eye, eye redness, and cylindrical dandruff) were reduced significantly ( P < 0.001) in patients who used the eyelash shampoo with TTO. The symptom scores remained almost the same in patients who used TTO-free eyelash shampoo ( P > 0.05). In conclusion, it was determined that eyelash shampoo with TTO is 3 times more effective at achieving full Demodex reduction, significantly reducing the Demodex count, and relieving ocular symptoms in patients where full reduction cannot be attained, without adverse side effects.

Can the tea tree oil (Australian native plant: Melaleuca alternifolia Cheel) be an alternative treatment for human demodicosis on skin?

Australian tea tree oil (TTO) and its extract terpinen-4-ol (T4O) are found to be effective in moderating demodex-related diseases. Their possible effects are lowering the mite counts, relieving the demodex-related symptoms and modulating the immune system especially the inflammatory response. This review summarizes the topical treatments of TTO and T4O in human demodicosis, their possible mechanism of actions, side-effects and potential resistance in treating this condition. Although current treatments other than TTO and T4O are relatively effective in controlling the demodex mite population and the related symptoms, more research on the efficacy and drug delivery technology is needed in order to assess its potential as an alternative treatment with minimal side-effect profile, low toxicity and low risk of demodex resistance.

The efficacy of tea tree face wash, 1, 2-Octanediol and microblepharoexfoliation in treating Demodex folliculorum blepharitis.

PURPOSE: To compare the efficacy of Dr Organic Tea Tree Face Wash, OcuSoft Lids Scrub Plus and the BlephEx™ device at treating of Demodex folliculorum blepharitis. METHODS: Eighty-six subjects (33 males/36 females) were enrolled in a randomised controlled interventional treatment study. Subjects completed a dry eye symptom questionnaire and were assessed for presence of Demodex folliculorum. Subjects were divided into three groups according to treatment: Dr Organic Tea Tree Face Wash (A) (n=28), OcuSoft Lid Scrub Plus (B) (n=30), or in-house lid scrub with the BlephEx™ device before nightly lid scrubs with OcuSoft Lid Scrub Plus (C) (n=28). Subjects were advised to clean their eyelids nightly for four weeks. Each subject was re-assessed for symptoms and Demodex folliculorum blepharitis after two weeks and four weeks of treatment. RESULTS: The quantity of Demodex folliculorum was significantly reduced after four weeks of treatment in all three groups (p<0.05). Overall, there was no difference in efficacy between the three treatments (p>0.1). Symptoms reported by subjects were significantly improved after two and four weeks of treatment (p<0.05). Overall, there was no difference in efficacy between the three treatments to reduce symptoms after two or four weeks (p= 0.813 and p=0.646 respectively). CONCLUSION: All three methods tested have shown good ability to reduce Demodex folliculorum quantity, improve subjective symptoms and help treat Demodex folliculorum blepharitis.

Elucidating the mechanisms underlying the beneficial health effects of dietary pollen on honey bees (Apis mellifera) infested by Varroa mite ectoparasites.

Parasites and pathogens of the honey bee (Apis mellifera) are key factors underlying colony losses, which are threatening the beekeeping industry and agriculture as a whole. To control the spread and development of pathogen infections within the colony, honey bees use plant resins with antibiotic activity, but little is known about the properties of other substances, that are mainly used as a foodstuff, for controlling possible diseases both at the individual and colony level. In this study, we tested the hypothesis that pollen is beneficial for honey bees challenged with the parasitic mite Varroa destructor associated to the Deformed Wing Virus. First, we studied the effects of pollen on the survival of infested bees, under laboratory and field conditions, and observed that a pollen rich diet can compensate the deleterious effects of mite parasitization. Subsequently, we characterized the pollen compounds responsible for the observed positive effects. Finally, based on the results of a transcriptomic analysis of parasitized bees fed with pollen or not, we developed a comprehensive framework for interpreting the observed effects of pollen on honey bee health, which incorporates the possible effects on cuticle integrity, energetic metabolism and immune response.

Acaricidal activities of the essential oil from Rhododendron nivale Hook. f. and its main compund, δ-cadinene against Psoroptes cuniculi.

In this paper, the acaricidal activities of Rhododendron nivale Hook. f. and its main compound, δ-cadinene were investigated, and the chemical composition of the essential oil was analyzed. The results showed that among aqueous, 70% ethanols, acetic ether, chloroform, petroleum ether and essential oil extracts from the shoots and leaves, the essential oil showed the best in vitro acaricidal activity against adult P. cuniculi, which occurred in a concentration- and time-dependent manner. The median lethal time (LT50) values of four concentrations (33.33-4.17mg/ml) of the essential oil ranged from 1.476 to 25.900h, respectively. After the treatment of P. cuniculi with the essential oil and ivermectin, infected rabbits were free of scabs or secretions in the ear canal by day 20. Then, the percent yield of essential oil from the leaves and shoots was 2.45% (w/w), which includes 50 compounds. The primary component identified was terpenes, and among of compounds identified from the essential oil of R. nivale the highest relative content was δ-cadinene, which also presented the marked acaricidal activity against Psoroptes cuniculi in vitro. These findings provide evidence for the use of acaricides as a traditional medicine and indicate that the essential oil and δ-cadinene could be used to control mites in livestock.

Sustained release ivermectin-loaded solid lipid dispersion for subcutaneous delivery: in vitro and in vivo evaluation.

This work aimed to develop a sustained release solid dispersion of ivermectin (IVM-SD) in a lipid matrix (hydrogenated castor oil, HCO) for subcutaneous delivery. Solvent-melting technology was employed to prepare IVM-SDs using HCO. The physicochemical properties of the IVM-SDs were evaluated by scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). The release of IVM from IVM-SDs was evaluated with HPLC in vitro. Pharmacokinetics of IVM was studied in rabbits following a single subcutaneous administration of IVM-SD formulations. The efficacy of IVM-SD against the ear mange mite was evaluated in rabbits. IVM was completely dispersed in HCO in an amorphous state at a drug:carrier ratio lower than 1:3. No chemical interactions between drug and carrier were found besides hydrogen bonding for the amorphous IVM-SDs. The amorphous IVM-SDs formulations exhibited a sustained release of IVM versus physical mixtures (PMs) of IVM and HCO. The drug release decreased as the drug:carrier ratios decreased, and the release kinetics of IVM were controlled via diffusion. Cytotoxicity of IVM-SD to MDCK cells was lower than native IVM. The IVM plasma concentration of SD1:3 remained above 1 ng/mL for 49 d. Higher AUC, MRT, and Tmax values were obtained at a SD1:3 relative to the IVM group. The IVM-SD improved almost 1.1-fold bioavailability of drug compared with IVM in rabbits. IVM-SD could provide longer persistence against rabbit's ear mites than a commercial IVM injection. This study shows that these solid lipid dispersions are a promising approach for the development of subcutaneous IVM formulations.

[Demodex folliculorum a hidden cause of blepharitis].

UNLABELLED: Meibomian gland dysfunction (MGD) is a common cause of dry eye disease. Demodex mites can cause MGD with symptoms like itching, dryness and general ocular discomfort. It is important to consider infestation with Demodex mites in individuals who are non responsive to traditional MGD treatment but also equally important when cylindrical dandruff is seen at the base of the eye lashes.. We report two individuals who had not responded to ocular and systemic treatment for MGD and were then diagnosed with Demodex mites. Treatment with BlephEx and Tea tree oil was successful. This is the first report on Demodex folliculorum in Iceland where a genetic analysis was done. KEY WORDS: Demodex, blepharitis, debris, tea tree oil, dry eye. Correspondence: Sigurlaug Guðrún Gunnarsdóttir sigurlaug@sjonlag.is.

Demodex treatment in external ocular disease: the outcomes of a Tasmanian case series.

Demodex species (spp.) have previously been implicated in the pathogenesis of blepharitis. This study aims to correlate improvement in symptoms of external ocular disease with treatment of underlying Demodex spp. This is a prospective, observational case series of patients with chronic external ocular disease. Demodicosis was confirmed by microscopic examination of epilated eyelashes. The main outcome measure was response to the treatment (5 % tee tree oil) in regard to change in subjective symptoms utilising a symptom-based patient questionnaire assessment. Overall patients had a good response to the treatment in terms of improvement or resolution of symptoms, with 91 % of patients reporting at least some improvement in symptoms. The treatment of underlying Demodex spp. appears to result in improvement of symptoms in patients with long standing external ocular disease and underlying Demodex spp. infestation.

Recent advances on ocular Demodex infestation.

PURPOSE OF REVIEW: To summarize recent advances on ocular Demodex infestation. RECENT FINDINGS: Demodex infestation is a potential cause of ocular surface inflammation. The pathogenesis of Demodex in eliciting ocular surface inflammation has been further clarified. Cliradex is currently the treatment of choice, it comprises the most active ingredient of tea tree oil, that is terpinen-4-ol, which helps eradicate Demodex mites and reduce ocular surface inflammation. SUMMARY: Ocular demodicosis is a common but overlooked eye disease that manifests a number of morbidities. Demodex folliculorum causes chronic anterior blepharitis whereas Demodex brevis causes posterior blepharitis, meibomian gland dysfunction, recurrent chalazia, and refractory keratoconjunctivitis. The lash sampling and microscopic counting method and in-vivo confocal microscopy are key diagnostic methods. Cliradex shows promising potential to reduce Demodex counts with additional antibacterial, antifungal, and anti-inflammatory actions.

Treatment options for demodex blepharitis: patient choice and efficacy.

BACKGROUND: Demodex mites are microscopic parasites that live around hair follicles or sebaceous glands and may cause chronic blepharitis. The aim of this outcome analysis was to assess the efficacy and patient preferences with regard to the currently recommended treatment options. METHODS: All patients with microscopic evidence for Demodex blepharitis were informed about the currently published treatments and instructed about daily lid hygiene. Additional topical treatment options included tea tree oil (TTO) 5%, a cleansing foam containing 0.02% TTO (Naviblef®), and metronidazole 2% ointment. Systemic treatment options included oral ivermectin 6 mg on day 1 and 14 and metronidazole 500 mg twice daily for 10 days. All patients were reviewed after 2 months for symptoms and for a mite count on 10 epilated lashes. RESULTS: Ninety-four of 96 patients with Demodex blepharitis opted for an additional treatment. The mean mite count after 2 months of treatment were 13.3 with 5% TTO (n=6), 12.0 with 0.02% TTO (n=38), 9.4 with metronidazole ointment (n=5), 12.8 with ivermectin (n=27) and 22.0 with oral metronidazole (n=5). CONCLUSION: While there are several published treatment options available, none of these options seem to be clearly effective in Demodex blepharitis.

Acaricidal activity of 9-oxo-10,11-dehydroageraphorone extracted from Eupatorium adenophorum in vitro.

The acaricidal activity of the 9-oxo-10,11-dehydroageraphorone (euptox A), a cadenine sesquiterpene from Eupatorium adenophorum (E. adenophorum) against Sarcoptes scabiei and Psoroptes cuniculi was tested in vitro. A complementary log-log (CLL) model was used to analyze the data of the toxicity tests in vitro. The results showed euptox A had strong toxicity against mites, killing all S. scabiei at 3 and 4 mg/ml (m/v) concentration, while 4 mg/ml euptox A was also found to kill all P. cuniculi within a 4 h period. Similarly, 2, 3 and 4 mg/ml concentration of euptox A had strong toxicity against S. scabiei, with median lethal time (LT50) values at 0.687, 0.526, 0.326 h, respectively. 3 mg/ml and 4 mg/ml showed strong acaricidal action against P. cuniculi; the LT50 values were 0.693 and 0.493 h, respectively. The median lethal concentration (LC50) values were 1.068 mg/ml for Scabies mite and 0.902 mg/ml for P. cuniculi in 2 h. The results indicate that euptox A has strong acaricidal activity and may exploit as novel drugs for the effective control of animal acariasis.