Multidisciplinary perspectives in Demodex blepharitis: A new view of treatment from clinical, payer, and patient perspectives.

Demodex infestation is the cause of more than two-thirds of all cases of blepharitis in the United States. Although symptoms may include crustiness, redness, or itching of the eyelids, diagnosis can be accomplished through a simple examination of the eyelashes. The presence of a waste product of the Demodex mite, known as collarettes, on the base of the eyelashes is a pathognomonic sign of Demodex blepharitis. Demodex infestation that results in blepharitis may cause blockage and ultimately atrophy of the meibomian glands, worsening dry eye disease. Until recently, management of Demodex blepharitis has been limited by a lack of approved therapy options. Lotilaner ophthalmic solution 0.25%, the first approved therapy for treatment of Demodex blepharitis, has not only been shown to eradicate Demodex mites in one-half to two-thirds of patients following short-term treatment but also demonstrated continued benefits through 1 year of follow-up. In addition to managing Demodex blepharitis, treatment with lotilaner ophthalmic solution 0.25% may aid in the management of dry eye disease and other forms of ocular surface disease caused by complications of Demodex infestation. As a result, it is possible that successful management of Demodex blepharitis may reduce chronic use of health care resources dedicated to managing other chronic ocular conditions. As eye care professionals recognize Demodex infestation as a key mediator of ocular surface disease, increasing diagnostic awareness and addressing this underlying cause of Demodex blepharitis may reduce the need for specialist follow-up care, decrease the need for chronic therapy, and improve patient outcomes. Through routine screening for Demodex infestation and Demodex blepharitis, eye care professionals can now address an underlying factor in ocular surface disease to improve use of health care resources in the community.

Phthiriasis palpebrarum masquerading as blepharitis.

Pthiriasis palpebrarum, a rare condition caused by Phthirus pubis, can mimic blepharitis and manifest as intense itching, inflammation and eyelid redness. We describe a case of Pthiriasis palpebrarum in a young girl with right upper eyelid discomfort. A slit lamp examination revealed eggs on her eyelashes and adult lice on the eyelids' surface. Dermatology consultation confirmed the diagnosis and successful treatment followed. Family evaluation uncovered genital Phthiriasis pubis in her parents, who received appropriate treatment. This report emphasises the importance of accurate diagnosis and management of this masquerading condition by careful slit lamp and microscopic evaluation. It also highlights the significance of comprehensive family history and examination.

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.

Efficacy and Safety of Lotilaner Ophthalmic Solution 0.25% for the Treatment of Demodex Blepharitis: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Demodex blepharitis, often overlooked in ocular surface disease, involves Demodex mites, prevalent ectoparasites on human skin. Current treatments may not effectively eliminate these mites, prompting a need for targeted therapies. Lotilaner, an antiparasitic agent, shows promise. This systematic review and meta-analysis assesses 0.25% lotilaner ophthalmic solution's efficacy in reducing Demodex mite populations and its impact on ocular surface inflammation in Demodex blepharitis patients. METHODS: A comprehensive literature search was performed in the PubMed and Cochrane Library databases from inception until February 2024 to identify relevant trials investigating the use of lotilaner in patients with Demodex blepharitis. The included studies were assessed for quality, and a meta-analysis was conducted to determine the overall treatment effects of lotilaner. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated for binary variables. All statistical analyses were performed using the R Statistical Software. RESULTS: Five studies met the inclusion criteria and were included in this systematic review and meta-analysis. Lotilaner demonstrated significant efficacy in Collarette Cure [OR = 6.64; 95 % CI 3.78 to 11.04; p < 0.00001, I2 = 62 %] %], clinically meaningful collarette reduction [OR = 6.21; 95 % CI 3.67 to 10.49; p < 0.00001, I2 = 90 %], and achieving at least 1-grade collarette improvement [OR = 5.12; 95 % CI (2.96 to 8.88); p < 0.00001, I2 = 90 %] compared to the placebo group. The treatment also resulted in mite eradication [OR = 6.18; 95 % CI 4.67 to 6.18; p < 0.00001, I2 = 34 %], reduction in mite density [OR = 9.37; 95 % CI 5.36 to 16.36; p < 0.00001, I2 = 84 %], and erythema cure [OR = 2.29; 95 % CI 2.24 to 3.39; p < 0.00001, I2 = 5 %] and composite cure [OR = 7.05; 95 % CI 3.66 13. 61; p < 0.00001, I2 = 11 %]. The study suggests that lotilaner is a promising therapeutic option for collarette and associated symptoms, but the high heterogeneity in some outcomes and limited long-term data warrant further research to confirm its effectiveness and safety. CONCLUSION: This systematic review and meta-analysis provides robust evidence supporting the efficacy of 0.25% lotilaner ophthalmic solution in treating Demodex blepharitis. Approval of this targeted therapy represents a significant milestone in ophthalmology and offers a promising treatment option for patients with Demodex blepharitis. Eye care professionals should consider the potential benefits of lotilaner in managing and alleviating the symptoms associated with Demodex infestations on the eyelids. Further research and long-term follow-up studies are warranted to assess the safety and effectiveness of lotilaner in treating Demodex blepharitis.

Clinical spectrum in microbiologically proven Demodex blepharokeratoconjunctivitis: An observational study.

PURPOSE: To study the demographic, clinical, and microbiological profile of Demodex-related blepharokeratoconjunctivitis (BKC) at a tertiary eye care hospital. METHODS: This retrospective observational study was conducted from January 2016 to September 2022. It included 83 patients with microbiologically proven Demodex BKC who presented to the cornea department of our tertiary care eye center. The clinical, microbiological, and demographic data of the 83 cases were analyzed. RESULTS: Of the 83 cases, 57 (68.67%) were younger than 40 years, and 25 (30.12%) were below 20. Most patients presented with a good visual acuity of 20/40 or better (93 eyes; 84.55%). The disease was unilateral in 55 patients and bilateral in 28. Cylindrical dandruff was the predominant presentation noted in 61 eyes (54.95%), followed by corneal scarring in 47 eyes (42.34%) and corneal vascularization in 40 eyes (36.04%). On light microscopy, 87.95% of the positive samples were identified as Demodex folliculorum , 7.23% as Demodex brevis , and 6.02% remained unidentified. Tea tree oil and lid scrubs eradicated the disease in most patients clinically (75/83, 90.36%). CONCLUSION: The spectrum of BKC includes both lid signs and corneal involvement. It can be a cause of recurrent BKC and detection of the mite by microscopic evaluation of the lashes can confirm the diagnosis. In most cases, the tea tree oil can effectively manage this condition. However, low doses of topical steroids are needed to control the inflammation in patients with corneal involvement.

XdemvyTM (Lotilaner Ophthalmic Solution) 0.25% Topical Solution for the Treatment of Demodex Blepharitis.

XdemvyTM (lotilaner ophthalmic solution) 0.25% topical solution was recently approved for the treatment of Demodex blepharitis in adults aged ≥18 years. As an antiparasitic agent, lotilaner selectively inhibits gamma-aminobutyric acid chloride channels specific to the parasite and induces spastic paralysis, leading to death of Demodex blepharitis mites. In two randomized, double-masked, vehicle-controlled, multi-center, phase-3 clinical trials (Saturn-1 and Satuirn-2), lotilaner 0.25% topical solution was investigated for the treatment of Demodex blepharitis. Patients were assigned to receive either lotilaner 0.25% topical solution or vehicle (solution that did not contain lotilaner as an active ingredient) twice daily for 6 weeks. On day 43, lotilaner group demonstrated primary efficacy in achieving collarette cure ([collarette grade 0], Saturn-1: study group 44% [92/209], vehicle 7.4% [15/204]; Saturn-2: study group 56% [108/193], vehicle 12.5% [25/200]). Secondary efficacy was achieved by eradication of mite ([0 mite/lash], Saturn-1: study group 67.9% [142/209], vehicle 17.6% [36/304]; Saturn-2: study group 51.8% [99/193], vehicle 14.6% [29/200]), composite cure ([grade 0 collarette as well as grade 0 erythema], Saturn-1: study group 13.9% [29/209], vehicle 1.0% [2/204]; Saturn-2: study group 19.2% [37/193], vehicle 4% [8/200]), and erythema cure ([grade 0 erythema], study group 19.1% [40/209], vehicle 6.9% [14/204]; Saturn-2: study group 31.1% [60/193], vehicle 9.0% [18/199]). The adverse events were mild, with the most common being pain at instillation site. The recommended regimen for lotilaner 0.25% solution is one drop in each eye twice daily for 6 weeks.

Long-Term Outcomes of 6-Week Treatment of Lotilaner Ophthalmic Solution, 0.25%, for Demodex Blepharitis: A Noninterventional Extension Study.

PURPOSE: The aim of this study was to evaluate the long-term outcomes of lotilaner ophthalmic solution, 0.25%, in the treatment of Demodex blepharitis. METHODS: This observational, extension study included patients with Demodex blepharitis (N = 239) who completed the Saturn-1 study and presented for the day 180 visit. All participants were assessed at days 180 and 365 after the initiation of 6-week treatment with the study drug or its vehicle. RESULTS: The proportion of patients with 0 to 2 collarettes (grade 0) was significantly higher in the study group (N = 128 patients) than in the control group (N = 111 patients) (39.8% vs. 2.7% at day 180 and 23.5% vs. 2.9% at day 365; P < 0.0001). Similarly, the proportion of patients with ≤10 collarettes (collarette grade 0-1) in the study group was significantly higher than in the control group (70.3% vs. 18.0% at day 180 and 62.6% vs. 21.9% at day 365; P < 0.0001). In the study group, erythema continued to improve even after completion of the 6-week lotilaner treatment. No serious ocular adverse events were observed in the study group, and there was 1 treatment-related ocular adverse event in the study group, which was considered mild. CONCLUSIONS: After 6-week treatment with lotilaner ophthalmic solution, 0.25%, for Demodex blepharitis, no long-term concerns were observed during 1 year of follow-up. A high proportion of patients with 0 to 2 collarettes (grade 0) or ≤10 collarettes (collarette grade of 0 or 1) was observed throughout 1 year of follow-up, indicating that the efficacy of lotilaner ophthalmic solution, 0.25%, against Demodex blepharitis may last well after completion of therapy.

Role of Topical 5-Fluorouracil in Demodex -Associated Blepharitis.

PURPOSE: The aim of this study was to report clinical observations suggesting the efficacy of topical 1% 5-fluorouracil (5-FU) in treating Demodex -associated blepharitis. METHODS: An observational retrospective review of 13 eyes from 13 individuals with conjunctival neoplastic lesions and concomitant Demodex lash infestation that received topical 1% 5-FU eye drops. Patients underwent slit-lamp examination at each follow-up visit. Clinical photographs of the lash line were obtained after treatment initiation. In a subset of patients, lashes were epilated bilaterally and microscopically analyzed for presence of Demodex mites before and after treatment initiation. RESULTS: The mean age of the population was 68 ± 14 years (range: 30-84 years) and 92% were male. In all 13 patients, a marked reduction in cylindrical dandruff was noted in the treated eye by slit-lamp examination after 2 cycles of 5-FU. There was complete resolution of cylindrical dandruff in 10 of 13 treated eyes compared with 0 resolution of cylindrical dandruff in untreated eyes ( P = 0.0001). In the 6 patients who received epilation, the lashes from the treated eye showed no Demodex , whereas lashes from the fellow untreated eye revealed persistent Demodex . CONCLUSIONS: Topical 1% 5-FU shows efficacy in treating Demodex -associated blepharitis. Further studies are indicated to reproduce our findings and evaluate the potential use of 5-FU as a treatment ingredient.

Prevalence of Demodex spp. in patients with chronic blepharitis.

Blepharitis is a very common disease in ophthalmology, dermatology and allergy practice. It generally follows a chronic course and is frequently associated with objective and/or subjective symptoms such as epiphora, red eye, dandruff, gritty sensation, itching, burning, photophobia, and blurred vision. The purpose of this study is to analyze the prevalence of Demodex spp. in patients with symptoms of chronic blepharitis. An analytical cross-sectional study was conducted in the period between 2016 and 2020. All patients with symptoms of chronic blepharitis who underwent a parasitological test of eyelashes (Rapitest) in the Dermatology Department of the Hospital Italiano de Buenos Aires were included. Those with previously established blepharitis due to another infectious cause were excluded. We analyzed 972 patients. Sixty percent (n=585) underwent a positive Rapitest for the presence of Demodex spp. Seventy five percent (n=728) were women. There were no significant differences in the prevalence associated with sex (p=0.38). Among the patients positive for Demodex spp., 65% (n=628) were older than 60 years old. The most frequently associated symptom was itching, present in 35% (n=342). A statistically significant decrease in the number of consultations was observed during the cold months of the year (May-June-July-August). Our results show a high prevalence of Demodex spp. in patients with chronic blepharitis. As its presence reveals a direct association with age, we recommend looking for this parasite in this age group.

Prevalence of Demodex folliculorum and Demodex brevis in patients with blepharitis and chalazion.

PURPOSE: Demodex folliculorum and Demodex brevis are common ectoparasites on skin that also can lead to blepharitis and chalazion. The aim of our study is to determine the prevalence of Demodex spp. in eyelashes of patients diagnosed with chronic blepharitis and chalazion. METHODS: This study included 330 patients diagnosed with chronic blepharitis, 70 patients diagnosed with chalazion and 130 volunteers without any ocular problems. Patient eyelashes were examined under a light microscope at magnifications of × 40, × 100 and × 400. Demodex spp. were determined. RESULTS: Parasite prevalence was significantly higher in blepharitis (75.5%) and chalazion groups (70%) compared to the control group (16.2%) (p < 0.001). The prevalence of D. folliculorum in the blepharitis group and D. brevis in the chalazion group was found to be significantly higher compared to other groups (p < 0.05). The average number of mites per eyelash was found to be significantly higher in patients with Demodex positive blepharitis (p = 0.001) and in chalazion patients (p = 0.047) than in the control group. It has been determined that mite positivity increases with age in blepharitis and control groups (p < 0.05). In the group with blepharitis, it was found that mite positivity was significant in the presence of symptoms (p = 0.0001) and Demodex positivity decreased as the education level of individuals increased (p = 0.039). CONCLUSION: The results of the study show that Demodex spp infestations should be considered in chronic blepharitis and chalazion.

Efficacy of Topical Ivermectin 1% in the Treatment of Demodex Blepharitis.

PURPOSE: The purpose of this study was to evaluate the efficacy of topical ivermectin 1% cream application on the eyelashes in combination with eyelid hygiene in the treatment of Demodex blepharitis. METHODS: One hundred two eyes of 102 patients with symptomatic Demodex blepharitis were divided into 2 groups according to the use of topical ivermectin in this retrospective case-control study. The ivermectin group (n = 51) applied topical ivermectin 1% cream on the eyelashes for 15 minutes once weekly, but the control group (n = 51) did not. In both groups, eyelid hygiene was performed once daily. The Standard Patient Evaluation of Eye Dryness (SPEED) symptom questionnaire score, Oxford staining score, eyelid debris, eyelid redness/swelling, and telangiectasia were assessed during the follow-up visits. RESULTS: The mean follow-up periods of the ivermectin and control groups were 15.1 ± 9.7 weeks and 14.8 ± 8.6 weeks, respectively. The SPEED score and eyelid debris grade were significantly improved in both groups during the follow-up, although the SPEED score and eyelid debris grade showed greater changes in the ivermectin group than in the control group. The Oxford staining score, eyelid redness/swelling grade, and telangiectasia grade were significantly improved only in the ivermectin group but not in the control group. CONCLUSIONS: In patients with Demodex blepharitis, the use of topical ivermectin 1% cream for 15 minutes once weekly in addition to eyelid hygiene had more significantly improved symptoms, ocular surface staining, eyelid debris, redness/swelling, and telangiectasia as compared with eyelid hygiene alone. These findings support the efficacy of topical ivermectin 1% cream application in the treatment of Demodex blepharitis.

Effect of ocular demodicosis on the stability of the tear film and the tear break up time.

The aim of the study was to analyze the correlation between the presence of Demodex mites in the hair follicles of patients' eyelashes and the stability and break up time of the tear film assessed with the Non-Invasive Tear Break Up Times (NIBUT) method. 319 patients were included in the study (195 women, 124 men). The patients were divided into two groups: those with Demodex infestation and without visible symptoms of eyelid or eye surface diseases, and asymptomatic non-infested patients. The NIBUT analysis was performed with a 5 M keratograph (oculus). Non-invasive tests were performed to identify the first and mean values of the tear break up time. The first and mean tear break up time in the Demodex-infested group was lower than in the non-infested subjects. The difference was a highly statistically significant. There was a significant correlation with the age of the patients for the first break up time. The first break up time in both eyes decreased with the age of the Demodex-infested and non-infested patients. The NIBUT analyses indicate the impact of Demodex mites on the tear film stability. This may suggest possible association of demodicosis with dry eye syndrome.

Collarette Elimination and Demodex Mite Eradication with Topical Lotilaner Ophthalmic Solution, 0.25.

Purpose: To evaluate the efficacy of topical lotilaner ophthalmic solution, 0.25%, in patients with Demodex blepharitis. Methods: Eighteen adults with Demodex blepharitis, defined as >10 collarettes on the upper lid and/or mite density of ≥1.5 mites per lash (upper and lower), were treated bid for 42 days with the topical lotilaner ophthalmic solution, 0.25%. Contact lens wear, artificial eyelashes, and lid structural abnormalities were among the exclusion criteria. No other antibacterial, antiparasitic, or anti-inflammatory treatment or lid hygiene products were permitted. One eye of each patient was selected for analysis and assessed on day 7, 14, 28, and 42. Collarettes were graded at each visit, and mite density was evaluated by microscopy at each visit except day 7. Outcome measures were collarette elimination (≤2 lashes with collarettes) and mite eradication (0 mites). Drop tolerability, adverse events, visual acuity, and slit-lamp biomicroscopy were assessed. Results: Collarette elimination was achieved in 13/18 participants (72.2%) by day 42. Mean collarette grade (upper lid) declined from 3.56 ± 0.17 to 0.28 ± 0.11. Mite eradication was achieved in 14/18 participants (77.8%) by day 42. Mean mite density decreased from 2.63 ± 0.39 to 0.12 ± 0.08 mites/lash. Participants reported good tolerability. Adverse events were mild and transient and did not result in treatment discontinuation. Conclusion: Six weeks of at-home topical therapy with the lotilaner ophthalmic solution, 0.25%, was effective in eliminating the most common objective signs of Demodex blepharitis, with a collarette elimination rate of 72% and mite eradication in 78% of eyes by day 42. ISRCTN registration #: 24398865.

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.

Unilateral Phthiriasis Palpebrarum: A Case Study

Phthiriasis palpebrarum is a rare eyelid infestation caused by Phthirus pubis (pubic lice) that is often confused with other causes of blepharoconjunctivitis. In this study, we report the case of a 49-year-old male patient with phthiriasis palpebrarum who presented with itching and eye irritation in the left eye and had undergone treatment for conjunctivitis in the past month. Biomicroscopic examination revealed a dense population of motile and translucent lice and eggs, more intensely on the upper lid. For treatment, the lice were first cleaned mechanically, eyelashes were cut from the bottom, and eggs and lice were removed from the eye, after which petrolatum jelly (vsaseline) was applied to the lids for 10 days. In the control examination, no lice and eggs were observed.

Prevalence of Ocular Demodicosis in an Older Population and Its Association With Symptoms and Signs of Dry Eye.

PURPOSE: To evaluate associations between Demodex and its symptoms and ocular surface parameters in individuals with dry eye (DE). METHODS: A cross-sectional study of 119 individuals with DE symptoms or signs, grouped by the presence of ocular demodicosis, was performed. All individuals filled out questionnaires and underwent an ocular surface examination. Demographics, comorbidities, symptoms profiles, and ocular surface parameters were compared between the 2 groups. Multivariable regression analyses were used to determine which factors were associated with DE symptoms. Receiver operating curves analyses were performed to evaluate relationships between Demodex quantity and specific clinical phenotypes. RESULTS: Demodex was highly prevalent in our population (68.9%) with average counts of 4.2 ± 3.9. Individuals with and without Demodex had comparable demographics. Overall, symptoms profiles were similar between individuals with and without Demodex using the Dry Eye Questionnaire 5 and Ocular Surface Disease Index. Individuals with Demodex, however, were more likely to report itching (58.5% vs. 35.1%, P = 0.03), with increasing frequency in those with higher Demodex counts. Individuals with Demodex also had more severe eyelid abnormalities [cylindrical dandruff (CD) and lid vascularity] and a more unstable tear film but similar tear production and corneal staining when compared with individuals without Demodex. Neither Demodex nor ocular surface findings related to DE symptoms in multivariable analyses. Receiver operating curves analysis revealed Demodex counts ≥2 maximized sensitivity and specificity for both itching (64.7% and 59.0%, respectively) and CD (80.4% and 60.4%, respectively). CONCLUSIONS: Demodex is highly prevalent in an older population with DE. Symptom of itching and CD were the findings most specific for Demodex.

In which rosacea patients should Demodex in the eyelashes be investigated?

AIM: The aim of this study was to investigate the relationship between the presence of Demodex on the face and within the eyelash follicles in patients with rosacea. SUBJECTS AND METHODS: This prospective cross-sectional study included 80 participants, 40 patients with rosacea and 40 individuals with no rosacea as controls. The presence of Demodex on the face was assessed by standard superficial skin biopsy. Sixteen eyelashes were epilated from each patient and control. RESULTS: The rate of Demodex infestation and severe infestation on the face in patients with rosacea was significantly higher than the control group. Demodex count within the eyelash follicle was significantly higher in patients with erythematotelangiectatic type rosacea than the control group. There was no increase in blepharitis in rosacea patients but when blepharitis was present, the rate of the presence of Demodex was higher in this group. There was a statistically significant relationship between the presence of Demodex within the eyelashes and itchy eyes in people without blepharitis. CONCLUSION: When at least one Demodex is found on the face in rosacea patients, the eyelashes should be examined for effective treatment of the mite. Itchy eyes may be an important sign of the presence of Demodex in people without blepharitis.

Ocular Demodex: a systematic review of the clinical literature.

PURPOSE: There is increasing clinical and research interest in the potential contribution of Demodex to ocular surface disease. The aim of this systematic review was to summarise and synthesise current clinical evidence relating to the aetiology, diagnosis and treatment of ocular Demodex. RECENT FINDINGS: A comprehensive literature search was performed in OVID Medline, OVID Embase, and clinical trial registries, for studies published between 1990 and August 2019, examining Demodex on the ocular surface. The review included primary clinical research studies and systematic reviews of primary clinical research studies, where Demodex was considered in the context of the ocular surface and/or adnexa. Studies were categorised using the National Health and Medical Research Council evidence hierarchy. Risk of bias assessment was performed using validated tools for studies categorised as providing Level I or II evidence. A total of 87 studies were eligible for inclusion, including two systematic reviews. Most studies (60%) were observational, describing the prevalence of ocular Demodex in different clinical populations. There was a high degree of variability in the epidemiological data derived from cross-sectional aetiology studies. There was mostly consistent evidence to support an association between ocular Demodex and chronic blepharitis. Seven diagnostic test-accuracy studies were identified, which considered a range of techniques, including slit lamp examination for cylindrical eyelash collarettes and/or eyelash manipulation techniques, light microscopic evaluation of epilated eyelashes and in vivo confocal microscopy. There is currently no accepted gold-standard diagnostic method for ocular Demodex. For intervention studies, there was one systematic review, 11 published randomised trials, six trial registry entries, and nine case series. Despite a number of recent trials, the appropriate treatment regimen for ocular Demodex (including the optimal criteria and timing of an intervention) is not clearly established. CONCLUSIONS: This comprehensive narrative synthesis has captured the landscape of clinical evidence relating to the prevalence, aetiology, diagnosis and treatment of ocular Demodex. There remain opportunities to enhance understanding of its role in ocular surface disease, best diagnostic approaches and optimal treatment protocols.

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.