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Effectiveness of Oral Ivermectin Treatment in Cases Unresponsive to Classical Demodex Blepharitis Treatment
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Original Investigation
E-PUB
11 September 2025

Effectiveness of Oral Ivermectin Treatment in Cases Unresponsive to Classical Demodex Blepharitis Treatment

Turkiye Parazitol Derg. Published online 11 September 2025.
Oktay Alver 1
Derya Doğanay 2
Selim Doğanay 3
1. Bursa Uludağ University Faculty of Medicine, Department of Medical Microbiology, Bursa, Türkiye
2. Çekirge State Hospital, Clinic of Ophthalmology, Bursa, Türkiye
3. Bursa Uludağ University Faculty of Medicine, Department of Ophthalmology, Bursa, Türkiye
No information available.
No information available
Received Date: 16.03.2025
Accepted Date: 26.08.2025
E-Pub Date: 11.09.2025
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ABSTRACT

Objective

Demodex blepharitis is a common inflammatory eye condition caused by an overgrowth of Demodex mites on the eyelids, and lash follicles, Zeiss’ glands and Meibomian glands that is often overlooked. The aim of this study is to investigate the effectiveness of ivermectin tablet oral treatment in cases unresponsive to classical Demodex blepharitis treatment.

Methods

A total of 35 patients (17 men and 18 women) with chronic symptomatic blepharitis were included in the study. Patients were admitted to Çekirge State Hospital and Bursa Dünyagöz Hospital Ophthalmology Clinics between December 12, 2017, and April 15, 2021, and were found to have Cylindrical dandruff resistant to classical Demodex blepharitis treatment. Followingthe classical Demodex treatmentin these cases, oral ivermectin was started in two doses of 0.2 mg/kg, 30 days apart. The presence of Demodex in the eyelashes, ocular surface disease index (OSDI) score was evaluated before the classical Demodex blepharitis treatment and after the ivermectin treatment. A detailed biomicroscopic eye examination was performed in all cases.

Results

Of the total 35 patients admitted to the hospital, 17 (48.6%) were men [mean ± standard deviation (SD): 48.41±15.62, min-max: 18-75] and 18 (51.4%) were women (mean ± SD: 51.17±14.98, min-max: 19-73). There was no statistically significant difference between men and women in terms of average age (p=0.598). OSDI scoring mean ± SD values before classical Demodex blepharitis treatment and after oral ivermectin treatment were 77.47±5.74 and 6.69±4.71, respectively.

Conclusion

In the treatment of Demodex related blepharitis, the use of oral ivermectin is an effective treatment option in cases that do not respond to classical treatment.

Keywords:
Demodex sp., blepharits, oral ivermectin, Bursa, Türkiye

INTRODUCTION

Demodex mites are arthropods that belong to the class Arachnida, the order Prostigmata and family Demodicidae (1). It is the most common host-dependent microscopic ectoparasite in humans (2). The family Demodicidae is represented by eight genera and 116 species that live as parasites on mammals (3), while only two of them (Demodex folliculorum and Demodex brevis) live in the pilosebaceous units of human skin (4). While D. folliculorum is 0.35-0.4 mm long and lives singly or in groups in hair follicles, D. brevis is 0.15-0.2 mm long and usually lives alone in the depths of the sebaceous glands. In the eyelids (Zeiss’ glands) and the lobules of the eyelid glands (Meibomian glands) (5, 6) and cause anterior and posterior blepharitis, respectively; D. folliculorum and D. brevis (7). Demodex blepharitis is a chronic inflammatory disease that can cause severe eye problems affecting the lid margin and ocular surface (7). The primary cause of demodectic blepharitis is no daubt the increase in the number of Demodex mites in the area. The plug and tension that occurs in the follicles due to increased number of Demodex mites can not only cause deformities in the eyelashes and dysfunction in the Meibomian glands, but also can cause a foreign body sensation and the development of an immune response against the chitin skeleton, as it deepens into the Meibomian glands (8). Accordingly, if left untreated, it may lead to severe lesions such as eyelid and eyelash abnormalities, blurred vision and corneal damage (9). It has been reported that 41.6-81.25% of blepharitis patients have concurrently developed symptoms related to Demodex mites, and this rate reaches 100% among people over 70 years (10).

The aim of this study is to probe further the response of systemic ivermectin treatment in blepharitis cases with Demodex infestation that do not respond to the classical treatment.

METHODS

The study was carried out in Bursa, the fourth most industrialized city in Türkiye. A total of 35 patients (17 men and 18 women) aged between 18 and 75 years, with chronic blepharitis, diagnosed with Cylindrical dandruff (CD) resistant to classical Demodex blepharitis treatment, were admitted to the Ophthalmology Clinics in Çekirge State Hospital and Bursa Uludağ University Faculty of Medicine, Bursa between December 12, 2017 and April 15, 2021, were included in the study. Data on demographic (age and gender), clinical characteristics (diabetes, hypertension, etc.), ocular symptoms (dry eye symptoms, eyelash loss, ingrown eyelashes, etc.), Demodex mite density, and ocular medications were obtained from patient records.

Ethical approval was obtained from the Clinical Research Ethics Committee of Bursa Uludağ University (permission no: 2021-14/18, date: 13/10/2021).

Collection and Examination of the Samples

A specialist medical parasitologist examined the eyelash samples. A total of 12 eyelash samples, three from the upper and lower lids of each eye, were taken by epilation method. Before taking samples, care was taken to avoid cosmetic products such as mascaras, eye shadows, eye liners. Eyelashes were placed on the slide, and then 2-3 drops of Hoyer’s medium were dropped on them and covered with a coverslip. The area was scanned using a light microscope with x40 magnification, and then inspected with a slightly closed diaphragm at x10 and x40 magnification, and the findings were noted. Participants whose sample materials are found to contain at least one egg, larva, nymph or mature forms of D. folliculorum or D. brevis were considered positive for Demodex (Figure 1).

Evaluation of Ocular Surface Parameters

The ocular surface examinations were performed in the following order: Slit lamp examination was conducted on palpebral margin, and checked for any congestion and shape irregularity of palpebral margin, blockage on the openning of the Meibomian gland, and backward displacement of the Meibomian gland orifice opening were evaluated using the scoring criteria reported in (Figure 2) (11).

Statistical Analysis

Statistical analysis of data was carried out using IBM SPSS Version 28.0 (IBM Corp. Released 2021. IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY: IBM Corp). The descriptive statistics are given as mean and standard deviation for quantitative data, and frequency and percentage for the qualitative data. Shapiro-Wilk test was used to examine the normality of variables. It is found that the collected data samples are normally distributed. T-test was used to compare the comparison of the two independent groups, and the paired t-test was used to compare the dependent variables. Pearson correlation coefficient was used to evaluate the relationship between variables. The statistical significance level was determined to be 0.05.

RESULTS

Of the total of 35 cases, 17 (48.6%) were men [mean ± standard deviation (SD): 48.41±15.62, min-max: 18-75] and 18 (51.4%) were women (mean ± SD: 51.17±14.98, min-max: 19-73). There was no statistically significant difference between men and women in terms of average age (p=0.598). All patients were over 18 years of age, while their mean age was 49.8±15.1 years. At their first visit to the clinic, 27 (77.1%) of patients were found to have dry eye complaints, 4 (11.4%) have eyelash loss, 3 (5.7%) have ingrown eyelashes (trichiasis), and 2 (5.7%) have itching complaints. In the study, each patient stated that they had had chalazion at least once. One patient stated that she was operated on once for chalazion, and another patient stated that she was operated on 4 times. Biomicroscopic examination revealed anterior blepharitis in 5 (14.3%) patients, posterior blepharitis in 6 (17.1%), anterior and posterior blepharitis in 23 (65.7%), and allergic conjunctival papillae in 5 (14.3%). D. folliculorum was detected in 32 of 35 cases (91.4%). Coexistence of D. folliculorum and D. brevis was detected in three patients (8.6%). Demodex sp. was detected in all CD patients in the biomicroscopic study, while keratitis was present in three patients. Three patients were taking prescribed medication for diabetes and hypertension, while two patients were taking medication for hypertension only. In 18 of the cases, Demodex sp. was found on the upper and lower eyelids of both eyes. There was no significant relationship between age and Demodex/eyelash in women (r=0.117; p=0.644), men (r=-0.175; p=0.503) and in all patients in general (r=-0.025; p=0.887). Before the application of ivermectin, the patients were treated doxycycline (tetradox® capsule 100 mg) 2x1 oral for 20 days, levofloxacin (levolon® 0.5% drops) 4x1 for two months, oxytetracycline hydrochloride+polymyxin b sulfate eye ointment (terramycin® 5 mg/10.000 IU eye ointment) 2x1 for two months, pilocarpine (pilosed® 2% drops) (massage to the eyelash roots with earwax 5 times a day) for two months, eye wash shampoo containing tea tree oil (TTO thermal®) (every evening eyelid cleaning) for six months. Demodex sp. was detected in the eyelash examinations of patients whose blepharitis symptoms did not completely disappear at the end of the second month despite the previous treatment given above. Two doses of oral ivermectin tablet (0.2 mg/kg) were administered, one month apart. As shown in Figure 1, after two months of oral ivermectin treatment, the blepharitis symptoms completely resolved and the parasite load was reduced in all patients. A statistically significant difference was found between ocular surface disease index (OSDI) values before and after treatment (p<0.001).

DISCUSSION

In a multicenter  retrospective study involving six optometry and ophthalmology clinics in the USA, the prevalence of Demodex blepharitis was reported as 57.7% (12). Many studies have reported an increase in the number of mites with age (13) which was explained by the decrease in the activity of the Rusiecka-Ziółkowska et al. (14) glands with aging. In the studies conducted on patients with blepharitis, as discussed by Sędzikowska et al. (15), Mongi et al. (16), and Wesolowska et al. (17) that they detected the highest Demodex sp. infestation rate on patients aged 50 years and above (p<0.005), 60 years and over (p<0.001), and 70 years and over (p<0.001), respectively. This may be associated with the lack of good eyelid hygiene in elderly patients and certain factors such as immunosuppression, vasodilatation factors, diabetes mellitus, and/or sebaceous gland hyperplasia (18) or malignancy, or malnutrition (19). As age increases, Demodex infestation rates tend to rise not only in the eyelashes but also on the face and other areas of the body (18). In the present study, the highest Demodex sp. infestation rate was determined in people aged 45 and over (68.5%), while no significant differences were found between age and Demodex sp. This finding was consistent with the results of numerous previous studies (p=0.598) (20, 21). Although there are many studies in the literature relating the number of Demodex to the gender of the patients, it still remains controversial. However, in this study, no relationship was found between the number of Demodex and the gender of the patients, supporting the results discussed by Lee et al. (6) and Kemal et al. (21). In other words, Okyay et al. (22) reported that Demodex sp. infestation was higher in men, while Forton et al. (23) and Zeytun (24) reported higher infestation rates in women, and Zhao et al. (25) reported equal rates in men and women. These differences between studies may be associated with the differences in skin care, type of skin, increase in the number of mites and hygiene practices of patients included in the study. Itching, burning sensation, excessive lacrimation, feeling of heaviness in the eyelids and mucous discharge are frequently encountered symptoms in blepharitis cases with Demodex infestation (26). Kheirkhah et al. (27) reported decreased vision in 50% of blepharitis cases caused by Demodex sp., and Meibomian gland dysfunction in 83.3%. Gao et al. (28) reported that they detected eyelash loss in 45.5% of the eyelid demodicosis cases, and Meibomian gland dysfunction in 63.6%. It is stated that the microabrasions caused by D. folliculorum at the base of the eyelashes cause reactive hyperkeratinization and epithelial hyperplasia, resulting in the formation of CD, which is accepted as pathognomonic for D. folliculorum infestation (28, 29). In Thailand, Kasetsuwan et al. (30) reported that they detected CD by microscopy in 69% and 15.5% of cases with and without ocular Demodex infestation, respectively. It has been stated that CD formation may be clinically valuable in monitoring the response to treatment in patients with chronic blepharitis (31). In the present study, all patients diagnosed with CD with chronic blepharitis, resistant to classical treatments, were found to be Demodex sp. positive. The number of Demodex sp. per eyelash before treatment was 1.63 (652/398). Today, the ambiguity in etiopathogenesis makes the treatment of blepharitis complicated. One of the primary aims of ocular demodicosis treatment is to reduce parasitic overpopulation in the lids and eyelashes and reduce inflammation by providing a better environment for the eye surface. There are many treatment options in the literature for this purpose. Although XDEMVY™ (lotilaner ophthalmic solution) is an FDA-approved preparation for the treatment of Demodex blepharitis, it is not being used in our country. In the treatment of blepharitis, the American Academy of Ophthalmology Blepharitis Preferred Practice Pattern recommends a combination of antibiotics, topical anti-inflammatories, and daily eyelid hygiene (32). The most frequently used approach to the eyelid hygiene is the use of gel, cream and shampoo forms of TTO, which is obtained by steam distillation from the leaves of Melaleuca Alternifolia (Indian laurel), or its most important acaricidal component, terpinen-4-ol (26). In previous studies Junk et al. (33) reported a remission rate of 71.6% in the fourth week of combined treatment of oral ivermectin and metronidazole (3x250 mg/day for three weeks) in patients with anterior blepharitis and valve lesions caused by Demodex sp. and also showed that combined treatment was more effective than ivermectin alone. In the treatment of inflammation on the palpebral edges, it was reported that local application of yellow mercury ointment, sulfuric ointment, anticholinesterase, antifungal drugs or antibiotics provided clinical improvement, but the best results were obtained after the application of metronidazole, mercury and erythromycin ointments (33). Holzchuh et al. (34), treated their patients with one dose of oral ivermectin (200 µg/kg) and repeated it after 7 days, and reported that the treatment had improved the symptoms of chronic blepharitis, with a 35.3% mite eradication rate. Symptoms caused by Demodex mites are difficult to treat and can take several months. This can be partly explained by the fact that the life cycle of Demodex sp. is approximately 14 days and the total life span is several weeks (4). Therefore, in this study, 8 weeks of treatment (approximately 4 life cycles of Demodex) were administered to evaluate recurrence of infestation. In another study, the mite eradication rate was expressed as 36% after four months of TTO shampoo treatment at low concentration (7.5%) to minimize the risks of possible side effects of TTO (35). In our study, there was little improvement in symptoms after the classical treatments of Demodex chronic blepharitis, when the presence of Demodex sp. was detected and a single dose of ivermectin was prescribed. No drug-related side effects were observed after treatment. At the end of the second month, improvement in the symptoms of blepharitis and a significant decrease in parasite load were observed. OSDI score is usually (generally) used in ophthalmology practice as it can directly indicate the degree of ocular surface inflammation. Zhang et al. (20) and Zeytun (24) reported that they found a significant increase in OSDI score in the ocular Demodex positive patient group. Pan and Chen (36) reported a significant correlation between Demodex count and OSDI score. Liu et al. (8) stated that there was a significant relationship between the number of Demodex, the OSDI score, and the severity of eye disease. Mergen et al. (37) reported that they found a negative relationship between the Demodex count and OSDI scores in patients with seborrheic blepharitis. In this study, a significant relationship was also found between the Demodex count and the OSDI score by performing correlation analysis.

CONCLUSION

Our study shows that oral ivermectin treatment may be beneficial especially in cases that do not respond to classical Demodex blepharitis treatments. However, we think that our results should be supported by more comprehensive randomized and prospective studies.

Ethics

Ethics Committee Approval: Ethical approval was obtained from the Clinical Research Ethics Committee of Bursa Uludağ University (permission no: 2021-14/18, date: 13/10/2021).
Informed Consent: Retrospective study.

Authorship Contributions

Surgical and Medical Practices: A.O., D.D., S.D., Concept: A.O., D.D., S.D., Design: A.O., D.D., Data Collection or Processing: A.O., D.D., Analysis or Interpretation: A.O., S.D., Literature Search: A.O., D.D., Writing: A.O., S.D.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.

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