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.

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.

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.

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.

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.

[Demodex and ocular surface disease]. / Demodex et pathologies de la surface oculaire.

Demodex is a saprophytic mite of the ocular adnexa, which can in certain circumstances proliferate on the skin of the face and on the eyelid margins. It is involved in facial rosacea (especially in the papulopustular form) and in the development or aggravation of anterior and/or posterior blepharitis or even keratoconjunctivitis, often in association with cutaneous lesions ; the pathophysiology is often multifactorial. Symptoms are non-specific, but the presence of cylindrical sleeves on the eyelashes is very suggestive of infestation, and certain techniques of biomicroscopic examination or imaging, such as confocal microscopy in vivo, allow direct visualization of the parasite. Parasitological examination of the eyelashes can confirm the diagnosis and can be improved by good sampling technique. Eyelid hygiene and oil-based ointments are the cornerstone of treatment. New specific treatments, in particular topical treatments based on tea tree oil, ivermectin, as well as pulsed light therapy and micro-exfoliation of the eyelid margin, can help to reduce the parasitic load and improve symptoms.

Double-Masked and Unmasked Prospective Study of Terpinen-4-ol Lid Scrubs With Microblepharoexfoliation for the Treatment of Demodex Blepharitis.

PURPOSE: To evaluate terpinen-4-ol lid scrubs (Cliradex) with Microblepharoexfoliation (MBE) (BlephEx) in the treatment of Demodex blepharitis. METHODS: An Institutional Review Board (IRB) approved the randomized prospective double-masked trial of 50 patients with Demodex positive blepharitis. All subjects were given an in-office MBE treatment and randomized to masked lid scrubs (terpinen-4-ol or sham) twice daily for 1 month. All subjects then returned for an additional MBE treatment and received open-label terpinen-4-ol scrubs twice daily for 1 month. OUTCOMES: Demodex levels, Ocular Surface Disease Index, tear osmolarity, MMP-9, Schirmer 1 and grading of the lid margin appearance, meibomian gland dropout, and meibomian gland secretions. RESULTS: Forty-six subjects (23 per group) were included for the analysis; 4 lost to follow up. Total Demodex folliculorum levels in the Cliradex group improved: 4.7 to 3.6 (first month interval P = 0.266) to 2.6 (second month interval P = 0.279), overall P < 0.05 over 2 months. Total levels in the sham group improved: 5.1 to 3.0 (first month interval P < 0.05) to 2.5 (second month interval P = 0.496), overall P < 0.05 over 2 months. No clear statistically meaningful improvements in other dry eye and blepharitis data metrics were observed. CONCLUSIONS: In-office MBE treatments combined with either Cliradex terpinen-4-ol medicated lid scrubs or sham scrubs showed a statistically significant reduction in D. folliculorum infestation levels; however, conclusions on clinical significance could not be made. In-office MBE with terpinen-4-ol lid scrubs showed no significant improvement over sham scrubs.

Ocular demodicosis: A review. / Demodicosis ocular: una revisión.

Demodex folliculorum and Demodex brevis are ectoparasites that inhabit the skin of humans. They have been related to alterations in the ocular surface, such as, dysfunction of Meibomian glands, blepharitis, chalazion, etc. Ocular demodicosis is characterised by the pathognomonic presence of cylindrical dandruff at the base of the eyelashes, and various symptoms including, among others, itching, lacrimation, and hyperaemia. A bibliographic review was carried out on the role of Demodex spp. in ocular disease, including publications made by the scientific society between 2005 and 2018. A significant relationship was found between prevalence and incidence of Demodex spp. in eye diseases. D. folliculorum is usually found more frequently than D. brevis in ocular infestation, with the prevalence or incidence of infestation by both species increasing with the age of the patient. In patients with blepharitis or other infectious diseases of the ocular surface, unresolved with antibacterial treatment, the search for Demodex spp. should be considered.

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.

[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.

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.

[Demodex folliculorum: diagnosis and therapy today]. / Demodex folliculorum: Diagnostik und Therapie im klinischen Alltag.

Demodex folliculorum is an ectoparasite found in eye lashes. A Demodex-associated blepharoconjunctivitis is common. Demodex are diagnosed via microscopy in a drop of oil after epilation of a few eye lashes. You can often watch the mites in movement under the microscope. Treatment includes lid hygiene and metronidazole gel 1-2 %. The treatment often improves the symptoms of the patient. Demodex folliculorum is often found in patients with persistent blepharoconjunctivitis. Every ophthalmologist should have a microscope to find the mites. Then you will be able to treat the patients in an early stage.

Ocular demodicidosis as a risk factor of adult recurrent chalazion.

PURPOSE: To report Demodex infestation in adult recurrent chalazion and its clinical response to weekly lid scrub with 50% tea tree oil (TTO) and daily lid scrub with tea tree shampoo. METHODS: This is a retrospective review of 30 adult patients (48 eyes) who presented with recurrent chalazion within 6 months after conventional treatment. Demodex was detected by random lash sampling and microscopic examination. Patients with confirmed ocular Demodex infestation were treated with weekly lid scrub with 50% TTO and daily lid scrub with tea tree shampoo. The study is limited by the lack of a control group. RESULTS: The mean age of patients was 39.1 ± 10.2 years (range 18-69). The mean follow-up of patients is 10.0 ± 3.0 months (range 6-24 months). Among 48 eyes with recurrent chalazion, Demodex mites were found in 35 (72.9%). Recurrent chalazion was found to be associated with ocular demodicidosis (Fisher exact test, p = 0.017). Tea tree oil treatment was given to 31 eyes with recurrent chalazion associated with Demodex infestation. Among the treatment group, all cases except one had no recurrence after the TTO treatment. The success rate of preventing recurrence is 96.8%. Treatment of TTO was found to be associated with preventing recurrence of chalazion associated with Demodex infestation (Fisher exact test, p = 0.002). CONCLUSIONS: The possibility of demodicidosis should be considered in adults presenting with recurrent chalazia. Tea tree oil eyelid scrubs is an effective treatment in preventing recurrence.

Ocular demodicosis as a potential cause of pediatric blepharoconjunctivitis.

PURPOSE: To report Demodex infestation in pediatric blepharoconjunctivitis. METHODS: A retrospective review of 12 patients, with ages from 2.5-11 years, with chronic blepharoconjunctivitis who failed to respond to conventional treatments. Demodex was detected by lash sampling and microscopic examination. Patients were treated with 50% tea tree oil (TTO) eyelid scrubs or 5% TTO ointment eyelid massages for 4-6 weeks. RESULTS: Demodex mites were found in all, but 1 case had cylindrical dandruff in the lashes. After 1 week of TTO treatment, all patients showed dramatic resolution of ocular irritation and inflammation while Demodex counts dropped. All corneal signs resolved within 2 weeks except for a residual anterior stromal scar in 1 eye. During a follow-up period of 8.3 ± 4.6 months, 1 patient showed recurrent inflammation, which was successfully managed by a second round of TTO treatment. CONCLUSIONS: Demodicosis should be considered as a potential cause of pediatric refractory blepharoconjunctivitis. Eyelid scrubs or massage with TTO could be an effective treatment regimen in these cases.

Corneal manifestations of ocular demodex infestation.

PURPOSE: To report the corneal manifestations in eyes with Demodex infestation of the eyelids. DESIGN: Noncomparative, interventional case series. METHODS: This retrospective review included six patients with Demodex blepharitis who also exhibited corneal abnormalities, which led to suspicion of limbal stem cell deficiency in three cases. All patients received weekly lid scrubs with 50% tea tree oil and a daily lid scrubs with tea tree shampoo for a minimum of six weeks. Improvement of symptoms and corneal and conjunctival signs were evaluated. RESULTS: All six patients exhibited ocular irritation and conjunctival inflammation, while meibomian gland dysfunction (n = 5), rosacea (n = 4), and decreased vision (n = 3) also were noted despite prior treatments with oral tetracycline, topical steroids with antibiotics, and lid scrub with baby shampoo. These patients were proven to have Demodex folliculorum (n = 6) and Demodex brevis (n = 3) by microscopic examination of epilated lashes. Their corneal manifestation included superficial corneal vascularization (six eyes of five cases), marginal corneal infiltration (two eyes of two cases), phlyctenule-like lesion (one eye of one case), superficial corneal opacity (two eyes of two cases), and nodular corneal scar (two eyes of two cases). After treatment, the Demodex count was reduced from 6.8 +/- 2.8 to 1 +/- 0.9 (standard deviation; P = .001). All patients showed dramatic resolution of ocular irritation, conjunctival inflammation, and all inflammatory, but not scarred, corneal signs; three patients showed improved vision. CONCLUSIONS: A variety of corneal pathologic features together with conjunctival inflammation, commonly noted in rosacea, can be found in patients with Demodex infestation of the eyelids. When conventional treatments for rosacea fail, one may consider lid scrub with tea tree oil to eradicate mites as a new treatment.