Evidence for the Clinical Association between Demodex and Rosacea: A Review.

BACKGROUND: Rosacea is a chronic inflammatory dermatological condition in humans, and its pathogenesis remains unclear. However, the development of rosacea is suspected to be related to Demodex, a microscopic commensal organism that resides in or near hair follicles and sebaceous glands. Although Demodex is known to be a host-specific, obligate commensal organism, it is currently difficult to be cultured in vitro to parasitize and infect other animal hosts. Therefore, direct evidence for a pathogenic role of Demodex in rosacea is currently lacking. SUMMARY: As circumstantial evidence, non-invasive skin-detecting techniques have shown abnormally elevated numbers of Demodex in rosacea patients. Increased cytokine levels such as IL-10, IL-8, and IL-12p70 have been observed in human sebocytes following the Demodex challenge, and acaricides have been found to be effective in rosacea therapy, all point to a close relationship between Demodex and rosacea. Based on these findings, we conducted a comprehensive literature review to summarize the current state of knowledge, research insights, and clinical treatment recommendations for Demodex-associated rosacea, with the ultimate goal of improving patient outcomes.

The varied influence of ocular Demodex infestation on dry eye disease and meibomian gland dysfunction across different age groups.

This study aimed to investigate the impact of ocular demodicosis on dry eye disease (DED) and meibomian gland dysfunction (MGD) across different age populations: young (20 to < 40), middle-aged (40 to < 60), and elderly (≥ 60), based on the retrospective medical chart review. In each age subgroup, Demodex infestation and its count were correlated with clinical parameters of DED and MGD. Among the total of 351 subjects, 52.7% had ocular demodicosis, with a mean of 2.31 ± 1.39 mites per four eyelashes (0.58 per lash) in a unilateral eye. In the age subgroup 1 (age < 40; N = 44), subjects with Demodex had significantly higher meibum quality grades. In subgroup 2 (40 ≤ age < 60; N = 122), subjects with Demodex had higher ocular surface disease index scores and higher MG expressibility grades. However, in subgroup 3 (age ≥ 60; N = 185), demographics and all parameters did not differ according to Demodex infestation. Moreover, the number of mites did not correlate with MGD severity in any of the subgroups. In conclusion, age may act as a significant confounding factor in the relationship between ocular Demodex infestation and clinical features of DED and MGD, despite older patients aged 60 years and above being at a higher risk of Demodex infestation and experiencing more severe MGD.

Cutaneous neurogenic inflammation mediated by TRPV1-NGF-TRKA pathway activation in rosacea is exacerbated by the presence of Demodex mites.

BACKGROUND: Rosacea is a common chronic inflammatory skin condition that is often refractory to treatment, with frequent relapses. Alterations in the skin immunological response and Demodex mite infestation are the primary aetiologic factors targeted for treatment. Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a nociceptive cation channel that plays a role in cutaneous neurogenic pain and can be activated by various rosacea triggers. OBJECTIVES: We investigated the effects of TRPV1 modulation in rosacea, focussing on Demodex mite colonization and cutaneous neurogenic inflammation. METHODS: We examined mRNA expression levels according to Demodex population counts. An in vitro study using capsazepine as a TRPV1 antagonist was performed to assess the influence of TRPV1 in keratinocytes. A rosacea-like mouse model was generated by the injection of the 37-amino acid C-terminal cathelicidin peptide (LL37), and changes in the skin, dorsal root ganglion (DRG) and ears were examined. RESULTS: Increased Demodex mite population counts were associated with increased expression levels of TRPV1, tropomyosin receptor kinase A (TrkA) and nerve growth factor (NGF), and these levels could be reduced by capsazepine treatment in keratinocytes. In an in vivo study, the downstream effects of TRPV1 activation were investigated in the skin, DRG and ears of the rosacea-like mouse model. CONCLUSIONS: The findings of this study are instrumental for understanding the underlying causes of rosacea and could potentially lead to the development of new treatments targeting the NGF-TrkA-TRPV1 pathway. The identification of this pathway as a therapeutic target could represent a major breakthrough for rosacea research, potentially resulting in more effective and targeted rosacea treatments. This study contributes to an improved understanding of rosacea pathophysiology, which may lead to the development of more effective treatments in the future.

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.

Iatrogenic Demodex folliculitis: A case report.

Demodex folliculorum is a commensal mite that inhabits the orifices of cutaneous pilosebaceous follicles. Overgrowth of these organisms can lead to Demodex folliculitis, which typically presents as papules and pustules predominantly involving the temples, cheeks, and occasionally the chest. We present a 51-year-old woman with iatrogenic Demodex folliculitis secondary to immunosuppressive treatment for an autoimmune connective tissue disease. Histopathological exam of a skin biopsy, which revealed follicular Demodex mites, confirmed the diagnosis. The eruption was treated with oral ivermectin and topical metronidazole gel, and the patient's immunosuppressive regimen was decreased, resulting in marked improvement in the eruption within 6 weeks and no worsening of her underlying autoimmune disorder. This case emphasizes the importance of considering Demodex folliculitis in the differential diagnosis of a new onset rash in the context of immunosuppressive treatment.

High Prevalence of Demodex Infestation is Associated With Poor Blood Glucose Control in Type 2 Diabetes Mellitus: A Cross-Sectional Study in the Guangzhou Diabetic Eye Study.

PURPOSE: The aim of this study was to investigate the association between type 2 diabetes mellitus (T2DM) and ocular Demodex mite infection. METHOD: About 381 patients with T2DM from nearby communities were enrolled, and 163 age-matched and sex-matched nondiabetic patients from the cataract clinic were included as the control group. All subjects underwent personal history and demographic data collection, ocular examination, and lash sampling, followed by microscopic identification and counting of Demodex mites. Binocular fundus photography was performed for diabetic patients. Statistical correlation between ocular Demodex infestation and T2DM and blood glucose control status was performed. RESULTS: The Demodex mite infestation rate (62.5% vs. 44.8%, P < 0.001) and count [3 (0-12) vs. 2 (0-9.6), P = 0.01], especially of Demodex brevis (18.9% vs. 4.9%, P < 0.001) [0 (0-1) vs. 0 (0-0), P < 0.001], were significantly higher in the T2DM patient group than that in the control group. The ratio of Demodex brevis to Demodex folliculorum in the T2DM patient group was significantly higher than that in the control group (1:3 vs. 1:9, P < 0.001). Diabetic patients presented with more cylindrical dandruff (55.1% vs. 39.3%, P = 0.001). Ocular Demodex infestation was strongly associated with poor blood glucose control (HbA 1 c > 7%) (odds ratio = 1.82; 95% confidence interval, 1.12-2.94; P = 0.2) and female sex (odds ratio = 1.69, 95% confidence interval, 1.08-2.65, P = 0.02). No association was found between Demodex infestation and the severity of diabetic retinopathy. CONCLUSIONS: Patients with T2DM, especially those with poor blood glucose control, tend to have a higher prevalence of ocular Demodex infestation, suggesting that high blood glucose is a risk factor for demodicosis .

Analysis of Demodex infection rate and risk factors in patients with meibomian gland dysfunction.

PURPOSE: In the present study, we aimed to investigate the positive rate of Demodex infection in patients with meibomian gland dysfunction (MGD) and to analyze its risk factors. METHODS: A total of 178 MGD patients admitted to the Jinan Second People's Hospital from April 2020 to February 2021 were enrolled in the present study. All patients were examined for Demodex infection, and their medical history was collected. The positive rate of Demodex infection was calculated after the examination. The medical history, including age, eating habits, pet ownership, and so on, was collected. First, a univariate analysis was conducted to identify the factors associated with positive Demodex infection, and then, a multivariate comprehensive analysis was carried out to identify the main risk factors for positive Demodex infection. RESULTS: In the present study, the positive rate of Demodex infection in 178 MGD patients was 73.60%. The risk factors of Demodex infection in MGD patients were gender, pet ownership, toiletry sharing, and diabetes (all P ≤ 0.15). Age was one of the risk factors for infection [B = 0.105, OR 1.111 (95%CI 1.069-1.155), P = 0.000], and toiletry sharing was more likely to cause positive Demodex mite infection [B = 0.891, OR 2.439 (95%CI 1.066-5.577), P = 0.035]. The Demodex infection was not statistically associated with gender (P = 0.234), pet ownership (P = 1.141), and diabetes (P = 0.295). CONCLUSIONS: The positive rate of Demodex infection was higher in MGD patients. The main risk factors affecting the positive rate of Demodex infection included age and toiletry sharing.

Type 2 Diabetes Mellitus and Demodex folliculorum Infestation: A Cross-Sectional Study in Peruvian Patients.

BACKGROUND: Demodex folliculorum is a mite that causes human demodicosis, which is characterized by producing lesions on the face, and its infestation could be associated with factors that alter the immune response, including Type 2 Diabetes (T2D). This study aimed to evaluate the relationship between T2D and D. folliculorum infestation in patients attended at a hospital in Peru in 2021. METHODS: A cross-sectional study enrolling patients who were classified according to the presence (n = 100) and absence (n = 100) of T2D was conducted. Information was obtained on age, sex, domestic animal husbandry, and symptoms and signs associated with demodicosis. Demodicosis was determined to be present when counts of D. folliculorum greater than five mites per cm2 were found in superficial facial skin biopsies. RESULTS: A frequency of demodicosis in 76 and 35 patients with and without T2D, respectively, was observed. In the multivariate analysis adjusted for confounders age, sex, and domestic animal husbandry, T2D was found to be associated with D. folliculorum infestation (PR: 2.13; 95% CI95: 1.42-3.19). CONCLUSIONS: T2D was associated with D. folliculorum infestation. In this sense, it is important to strengthen surveillance to identify of D. folliculorum infestation in people with T2D.

Asociación entre la infestación por el Demodex sp. y el acné vulgar grave. Estudio transversal de 168 pacientes / Association Between Demodex Infestation and Severe Acne Vulgaris: A Cross-Sectional Study of 168 Patients

Antecedentes y objetivos Existen antecedentes de asociación de la infestación por Demodex sp. y el acné vulgar. El objetivo fue evaluar si la infestación por Demodex sp. se asocia a acné vulgar grave en consultas externas del Hospital Regional Lambayeque. Material y métodos Estudio trasversal en 46 pacientes con acné grave y 92 pacientes con acné no grave. Se definió como acné vulgar grave al de los participantes que tuvieron un grado ≥ 3 con la escala de gravedad del acné en español (EGAE). La infestación por Demodex sp. se determinó mediante biopsia cutánea superficial, considerándose infestación si existieron más de 5 ácaros por cm2. Resultados El 60,9% de los participantes fueron del sexo masculino, con una mediana de edad de 18 años y un rango intercuartílico de 15 a 20 años, provenían del sector urbano (81,9%) y se encontró infestación por Demodex sp. en el 29,7%. En el análisis bivariado, se encontró asociación estadísticamente significativa entre acné vulgar grave e infestación por Demodex sp. (p=0,001), sexo (p=0,003), procedencia (p=0,015), antecedente paterno de acné (p=0,045), antecedente materno de acné (p=0,045) y tipo de piel (p<0,001). En el análisis multivariado la infestación por Demodex sp. estuvo 4,2 veces más asociada a acné vulgar grave (IC 95%: 1,6-10,9; p=0,003) ajustado por sexo, procedencia urbana, tratamiento previo, antecedentes paterno y materno de acné vulgar y presencia de piel grasa. Conclusiones La infestación por Demodex sp. se asocia al acné vulgar grave (AU)

Background and objectives Infestation with Demodex mites has been associated with acne vulgaris. The aim of this study was to explore the association between Demodex infestation and severe acne vulgaris in outpatients seen at Hospital Regional Lambayeque in Chiclayo, Peru. Material and methods We conducted a cross-sectional study of 46 patients with severe acne and 92 patients with nonsevere acne. Severe acne vulgaris was diagnosed if the score was 3 or more on the Spanish Acne Severity Scale (EGAE, in its Spanish acronym). Demodex infestation was diagnosed when a skin surface biopsy showed more than 5 mites/cm2. Results The patients had a median age of 18 years (interquartile range, 15-20 years), 60.9% were male, 81.9% lived in an urban area, and 29.7% were infested with Demodex mites. In the bivariate analysis, severe acne vulgaris was significantly associated with Demodex infestation (P=.001), sex (P=.003), residence (P=.015), a paternal history of acne (P=.045), a maternal history of acne (P=.045), and type of skin (P<.001). In the multivariate analysis, after adjustment for male sex, urban residence, previous treatment, maternal and paternal history of acne vulgaris, and an oily skin type, patients with Demodex infestation were 4.2 times more likely to have severe acne vulgaris (95% CI: 1.6-10.9, P=.003). Conclusion Demodex infestation was associated with severe acne vulgaris in outpatients at our hospital (AU)

[Translated article] Association Between Demodex Infestation and Severe Acne Vulgaris: A Cross-Sectional Study of 168 Patients / Asociación entre la infestación por el Demodex sp. y el acné vulgar grave: estudio transversal de 168 pacientes

Background and objectives Infestation with Demodex mites has been associated with acne vulgaris. The aim of this study was to explore the association between Demodex infestation and severe acne vulgaris in outpatients seen at Hospital Regional Lambayeque in Chiclayo, Peru. Material and methods We conducted a cross-sectional study of 46 patients with severe acne and 92 patients with nonsevere acne. Severe acne vulgaris was diagnosed if the score was 3 or more on the Spanish Acne Severity Scale (EGAE, in its Spanish acronym). Demodex infestation was diagnosed when a skin surface biopsy showed more than 5 mites/cm2. Results The patients had a median age of 18 years (interquartile range, 15-20 years), 60.9% were male, 81.9% lived in an urban area, and 29.7% were infested with Demodex mites. In the bivariate analysis, severe acne vulgaris was significantly associated with Demodex infestation (P=.001), sex (P=.003), residence (P=.015), a paternal history of acne (P=.045), a maternal history of acne (P=.045), and type of skin (P<.001). In the multivariate analysis, after adjustment for male sex, urban residence, previous treatment, maternal and paternal history of acne vulgaris, and an oily skin type, patients with Demodex infestation were 4.2 times more likely to have severe acne vulgaris (95% CI: 1.6-10.9, P=.003). Conclusion Demodex infestation was associated with severe acne vulgaris in outpatients at our hospital (AU)

Antecedentes y objetivos Existen antecedentes de asociación de la infestación por Demodex sp. y el acné vulgar. El objetivo fue evaluar si la infestación por Demodex sp. se asocia a acné vulgar grave en consultas externas del Hospital Regional Lambayeque. Material y métodos Estudio trasversal en 46 pacientes con acné grave y 92 pacientes con acné no grave. Se definió como acné vulgar grave al de los participantes que tuvieron un grado ≥ 3 con la escala de gravedad del acné en español (EGAE). La infestación por Demodex sp. se determinó mediante biopsia cutánea superficial, considerándose infestación si existieron más de 5 ácaros por cm2. Resultados El 60,9% de los participantes fueron del sexo masculino, con una mediana de edad de 18 años y un rango intercuartílico de 15 a 20 años, provenían del sector urbano (81,9%) y se encontró infestación por Demodex sp. en el 29,7%. En el análisis bivariado, se encontró asociación estadísticamente significativa entre acné vulgar grave e infestación por Demodex sp. (p=0,001), sexo (p=0,003), procedencia (p=0,015), antecedente paterno de acné (p=0,045), antecedente materno de acné (p=0,045) y tipo de piel (p<0,001). En el análisis multivariado la infestación por Demodex sp. estuvo 4,2 veces más asociada a acné vulgar grave (IC 95%: 1,6-10,9; p=0,003) ajustado por sexo, procedencia urbana, tratamiento previo, antecedentes paterno y materno de acné vulgar y presencia de piel grasa. Conclusiones La infestación por Demodex sp. se asocia al acné vulgar grave (AU)

Innate type 2 immunity controls hair follicle commensalism by Demodex mites.

Demodex mites are commensal parasites of hair follicles (HFs). Normally asymptomatic, inflammatory outgrowth of mites can accompany malnutrition, immune dysfunction, and aging, but mechanisms restricting Demodex outgrowth are not defined. Here, we show that control of mite HF colonization in mice required group 2 innate lymphoid cells (ILC2s), interleukin-13 (IL-13), and its receptor, IL-4Ra-IL-13Ra1. HF-associated ILC2s elaborated IL-13 that attenuated HFs and epithelial proliferation at anagen onset; in their absence, Demodex colonization led to increased epithelial proliferation and replacement of gene programs for repair by aberrant inflammation, leading to the loss of barrier function and HF exhaustion. Humans with rhinophymatous acne rosacea, an inflammatory condition associated with Demodex, had increased HF inflammation with decreased type 2 cytokines, consistent with the inverse relationship seen in mice. Our studies uncover a key role for skin ILC2s and IL-13, which comprise an immune checkpoint that sustains cutaneous integrity and restricts pathologic infestation by colonizing HF mites.

Could there be an association between Hashimoto's thyroiditis and demodex infestation?

BACKGROUND: Human demodex mites are parasites that live in the pilosebaceous unit and can result in the disease demodicosis. While demodicosis may occur as a primary skin disease; immunosuppression, and topical or systemic immunosuppressive treatments can cause secondary demodicosis. It is known that thyroid hormones may cause skin changes, such as xerosis, and thereby may also modulate immune responses in the skin. OBJECTIVES: The aim of this study is to investigate whether or not that the changes occurring in the skin of patients with Hashimoto's Thyroiditis (HT) predispose to demodex infestation. METHODS: Seventy-eight patients being followed for a diagnosis of HT at Kocaeli University Endocrinology Outpatient Clinic, between January 2019 and March 2020, constituted the patient group. The control group consisted of 41 patients who did not have any chronic systemic or dermatological disease and were shown to have no thyroid disease by laboratory tests. Demodex intensity in the malar regions of the patient and control groups was determined using the standardized skin surface biopsy (SSSB) method and compared with each other. RESULTS: HT patients were significantly more likely to have increased demodex density and suggestive SSSB results than the controls (p < 0.001, p = 0.012, respectively). A significant correlation was found between demodex intensity and the findings of xerosis (p = 0.010, p = 0.011) and spiny follicular papules (p = 0.008, p = 0.008) in the patient or control groups, respectively. However, a significant correlation was identified between the demodex density and the symptoms of burning-stinging (p = 0.028), and feelings of dryness (p = 0.018) roughness (p = 0.028) only in the control group. CONCLUSION: Xerotic skin and/or impaired immune responses as a result of autoimmune changes in patients with HT may lead to secondary demodicosis.

The association of demodex infestation with pediatric chalazia.

PURPOSE: This study aimed to investigate the association of Demodex infestation with pediatric chalazia. METHODS: In a prospective study, 446 children with chalazia and 50 children with non-inflammatory eye disease (controls) who underwent surgical treatment were enrolled from December 2018 to December 2019. Patient ages ranged from 7 months to 13 years old. All patients underwent eyelash sampling for light microscope examination, and statistical correlation analysis between Demodex infestation and chalazia, including the occurrence, recurrence, and course of disease, morphological characteristics, and meibomian gland dysfunction (MGD) in chalazia patients was performed. RESULTS: Demodex was found in 236 (52.91%) patients with chalazia and zero control patients. Demodicosis was significantly more prevalent in chalazia patients than the control group (P < 1 × 10- 14). Recurrent chalazia (P = 0.006) and skin surface involvement (P = 0.029) were highly correlated with Demodex infestation. Demodicosis was also associated with multiple chalazia (P = .023) and MGD(P = .024). However, Demodex infestation was comparable in the course of disease (P = 0.15), seasonal change (P = 0.68) and blepharitis subgroups (P = 0.15). Within the group of chalazia patients who underwent surgical removal of cysts, 4 (0.9%) patients with concurrent demodicosis experienced recurrence. CONCLUSIONS: Demodex infestation was more prevalent in pediatric chalazia patients than healthy children, and was associated with recurrent and multiple chalazia. Demodicosis should be considered as a risk factor of chalazia. In children with chalazia, Demodex examination and comprehensive treatment of Demodex mites should be applied to potentially prevent recurrence.

Rosacea, an infectious disease: why rosacea with papulopustules should be considered a demodicosis. A narrative review.

Rosacea and demodicosis are common facial conditions in dermatology practice. While demodicosis is clearly the result of Demodex mite infestation, the pathogenicity of rosacea is still not sufficiently explained, so that it is defined by its symptoms, and not by its cause. It is usually considered as a disease of the immune system associated with neurogenic inflammation triggered by various factors (ultraviolet light, heat, spicy food, alcohol, stress and microorganisms). Its links with demodicosis remain controversial, although there is increasing evidence that Demodex mites may play a key role in the inflammatory process. Indeed, high Demodex densities are observed in nearly all cases of rosacea with papulopustules (PPR) and the papulopustules of rosacea can be effectively treated with topical acaricidal agents. Recent studies suggest that Demodex induces two opposite actions on host immunity: a defensive immune response aimed at eliminating the mite and an immunosuppressive action aimed at favouring its own proliferation. Moreover, the initial defensive immune response is likely diverted towards benefit for the mite, via T-cell exhaustion induced by the immunosuppressive properties of vascular endothelial growth factor, which may also explain the favourable influence that the altered vascular background of rosacea seems to exert on Demodex proliferation. In this review, the evidence for and against a causal role of Demodex in rosacea is discussed, applying three systems traditionally used to attribute causality to a disease (modified Koch criteria, Hill criteria for causality and Rothman model). The findings suggest that PPR can reasonably be attributed to Demodex proliferation, which appears to be a necessary factor in the centre of a causal network in which multiple co-factors interact and influence the occurrence and severity of inflammatory symptoms, from limited (pityriasis folliculorum) to more marked (PPR). PPR could, therefore, be considered as a chronic infection by Demodex mites with associated T-cell exhaustion.

Demodex infestation as a cause of sensitive skin in a dermatology outpatient clinic.

BACKGROUND: Sensitive skin is subjective cutaneous hyperreactivity to environmental factors. Demodicosis is a skin disorder caused by Demodex mites. There may be a link between demodicosis and sensitive skin. AIM: This study aimed to examine facial Demodex mites density and other factors associated with sensitive skin in patients. METHODS AND METHODS: A total of 349 randomly selected patients presented to the dermatology department. The research data were collected using a questionnaire form that included the participants' sociodemographic and lifestyle characteristics, a sensitive skin questionnaire, the Dermatology Life Quality Index (DLQI), and European Health Interview Survey (EHIS). Patients underwent standardized superficial skin surface biopsy of 4 areas of the face. D. folliculorum count greater than 5 mites/cm2 was considered positive. RESULTS: In relation to Demodex, there was an increase in skin sensitivity with higher Demodex density (p = 0.04). There was a statistically significant, weak positive correlation between skin sensitivity and DLQI score (r = 0.33, p = 0.00), and there was also a significant but very weak negative correlation between skin sensitivity and EUROHIS (r = -0.164, p = 0.002). Skin sensitivity was more common in patients with a concomitant dermatological disease (p = 0.01) and increased with more frequent cosmetic use (p = 0.00). CONCLUSION: Alongside other risk factors, for the patients presenting with complaints of sensitive skin, investigating Demodex population density may help alleviate sensitive skin symptoms with appropriate therapies and preventive measures.

Safety and efficacy of lotilaner ophthalmic solution, 0.25% for the treatment of blepharitis due to demodex infestation: A randomized, controlled, double-masked clinical trial.

PURPOSE: To evaluate the safety and efficacy of lotilaner ophthalmic solution, 0.25% for the treatment of blepharitis due to Demodex infestation compared to vehicle control. METHODS: In this phase II, randomized, controlled, double-masked clinical trial, 60 eligible participants with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either topical lotilaner ophthalmic solution, 0.25% (Tarsus Pharmaceuticals, Inc., Irvine, CA) (study group) or the vehicle without lotilaner (control group) bilaterally twice a day for 28 days. Participants were followed at Days 7, 14, 28, 60 and 90. The efficacy parameters were change in collarette grade and Demodex density at Day 28. Safety parameters were adverse events, changes in corrected distance visual acuity (CDVA), intraocular pressure (IOP) and slit-lamp biomicroscopy. RESULTS: The study group showed a statistically significant decrease in collarette grade compared to the control group beginning at Day 14 (p = 0.003) in the upper eyelid and at Day 28 (p = 0.003) in the lower eyelid. Decreases in both lids were maintained through Day 90 (p < 0.001). At Day 28, mite eradication was achieved in 66.7% and 25.9% of eyes in the study and control group (p = 0.005); at Day 90, these proportions were 68.2% and 18.5% (p = 0.001), respectively. No serious adverse events or clinically significant changes in CDVA and IOP were observed. CONCLUSION: For Demodex blepharitis, treatment with lotilaner ophthalmic solution, 0.25% for 4 weeks is safe and effective. The improvement in collarette grade and mite density observed during the treatment period persisted for at least two months following treatment cessation.