Clinical Treatment of Ocular Demodex folliculorumby Systemic Ivermectin




Purpose


To report clinical outcomes of the treatment of ocular Demodex folliculorum with oral ivermectin.


Design


Noncomparative, interventional case series.


Methods


Setting. Institutional. Study Population . Twenty-four eyes of 12 patients (3 male and 9 female; mean age ± standard deviation, 50.4 ± 21.0 years) with refractory posterior blepharitis with the presence of D. folliculorum in lash samples were enrolled in this study. Intervention. Patients were instructed to take 1 dose of oral ivermectin (200 μg/kg). All patients were instructed to repeat the treatment after 7 days. Main outcome measures. Tear meniscus height, Schirmer I test results, noninvasive tear film break-up time (BUT), quantification of the absolute number of D. folliculorum found in the lashes, and corneal fluorescein and rose bengal staining scores were obtained from all patients 1 day before and 28 days after treatment.


Results


Statistical improvement was observed in the absolute number of D. folliculorum found in the lashes after the treatment with oral ivermectin. Average values of Schirmer I test results and tear film break-up time improved statistically after the treatment of oral ivermectin. No statistical improvement was observed in average lacrimal meniscus height or value of corneal fluorescein and rose bengal staining after treatment with oral ivermectin.


Conclusions


Ivermectin successfully reduced the number of D. folliculorum found in the lashes of patients with refractory blepharitis. Oral ivermectin may be very useful as a complement in the treatment of D. folliculorum infestation with ocular manifestation, especially in cases of unsuccessful treatment related to patient compliance.


Demodex (from Greek: demos = wax or fat; dex = insect) is a microscopic ectoparasite of Arachnid class and Acarina order. It is the most common permanent parasite in humans. Among the various species, only 2 are described on the human body surface: Demodex folliculorum longus and Demodex folliculorum brevis. Demodex tend to gather in the face, cheeks, forehead, nose, and external ear tract, where active sebum excretion provides a favorable habitat for breeding. Demodex folliculorum longus commonly is found in the infundibular portion of pilous follicle of the eyelash. Demodex folliculorum brevis is found in the deep ducts of sebaceous glands of the eyelash and meibomian glands. It is common to observe 3 or more parasites in a single follicle.


In the eye, it is believed that Demodex folliculorum has been related to blepharitis and ocular rosacea. However, it is still controversial because ocular symptoms are not always present in patients with Demodex. Low counts of Demodex can be found in individuals without symptoms. Its is believed that corneal manifestations of ocular Demodex are secondary to blepharitis.


Dermatologists have not been able to reach agreement concerning the physiopathology of Demodex. It is also controversial whether the mite is commensal or found coincidentally in skin diseases. Previous studies have shown a wide range of antiseptic solutions to control and eradicate D. folliculorum and its cysts such as salicylic acid, selenium sulphide, metronidazole, crotamitone, lindane, tea tree oil, and ivermectin associated with topical permethrin. The treatment of ocular Demodex is still controversial. Treatment of chronic rosacea-like dermatitis of the facial skin and eyelids using oral ivermectin and subsequent topical permethrin previously have been shown by other authors ; however, its efficacy in ocular manifestations is still unknown. The purpose of this study is to report clinical outcome of the treatment of ocular D. folliculorum by oral ivermectin.


Methods


Twenty-four eyes of 12 patients (3 male and 9 female; mean age ± standard deviation, 50.4 ± 21.0 years) with refractory posterior blepharitis diagnosed by a qualified ophthalmologist were enrolled in this study. This noncomparative, interventional case series was performed at the outpatient clinic of the Department of Ophthalmology, University of São Paulo School of Medicine (Hospital das Clínicas of Faculdade de Medicina da Universidade de São Paulo).


All patients enrolled in this study met the following criteria: (1) presence of signs and symptoms of chronic blepharitis; (2) previous systemic and topic treatments with no improvement; (3) presence of Demodex according to the method described below. Patients with (1) any systemic or topical antibacterial or anti-inflammatory drugs 60 days before study entry, (2) previous eye surgery or punctal occlusion, (3) contact lens wear, (4) presence of any corneal infection, (5) known hypersensitivity to ivermectin, (6) any corneal diseases (marginal ulcer, opacity, scar, bullous keratopathy, inflammation, edema, conjunctivochalasis, symblepharon, tumor), (6) any lid structural abnormalities, (7) any inflammation or active structural change, or both, in the iris or anterior chamber, (8) glaucoma, or (9) pregnancy were excluded from this study.


Tear meniscus height, Schirmer I test results, noninvasive tear film break-up time (BUT), quantification of the absolute number of D. folliculorum found in the lashes, and corneal fluorescein and rose bengal staining scores were obtained from all patients 1 day before and 28 days after the treatment of systemic ivermectin. Tear meniscus height was assessed using the slit illumination of the slit lamp and was measured in millimeters. Schirmer I test was assessed using a Whatman 41 paper strip (Ophthalmos, São Paulo, Brazil) placed in the lateral lower conjunctival sac, and the measurement after 5 minutes (closed eye) was recorded. Tear film BUT and rose bengal and fluorescein staining scores were obtained using 3 μl preservative-free combination of 1% rose bengal and 1% fluorescein into the conjunctiva sac according to double vital staining method described by Toda and Tsubota. Tear film BUT was measured 3 times and averaged. Ocular surface staining score was rated from 0 to 9 (0 = no staining, 1 = mild staining, 2 = moderate staining, and 3 = extensive staining) according to methods used by Toda and Tsubota.


A modified method of sampling and counting of Demodex were used in this study. The superior and inferior lid were divided in 3 areas (medial, central, and lateral), and 2 lashes were removed from each third of the superior and inferior area of both sides (a total of 12 lashes per side). The lashes were placed separately between 2 glass slides. Two percent metilcelulosis was used to embed the lash. Immediately, the number of Demodex was counted under magnification of 75 times using an optical microscope. The number of Demodex found in the lashes was recorded.


Patients were instructed to take 1 dose of oral ivermectin (200 μg/kg, 6-mg tablets). All patients were instructed to repeat the treatment after 7 days. All measurements were performed by 1 examiner (F.G.H.), under controlled temperature and humidity (variation of 20.10 ± 1.12 C and 62.58 ± 3.46%, respectively). Data are expressed as mean ± standard deviation. The Wilcoxon matched pairs test and Mann–Whitney U test were used in this study. The used level of significance was P < .05.




Results


The average and standard deviation of meniscus height, tear film BUT, Schirmer I test results, and fluorescein and rose bengal scoring before and after the treatment of oral ivermectin is shown in Table 1 . Average tear film BUT and Schirmer I values improved statistically after the treatment with oral ivermectin. No statistical improvement was observed regarding average values of meniscus height or corneal fluorescein and rose bengal scores with treatment with oral ivermectin.



TABLE 1

Average and Standard Deviation of Meniscus Height, Noninvasive Tear Film Break-up Time, Schirmer I Test Results, Rose Bengal Staining, and Fluorescein Score before and after the Treatment of Systemic Ivermectin in Patients with Ocular Demodex folliculorum


















































Before After P Value
Average SD Average SD
Tear film break-up time (sec) 7.49 4.17 8.92 4.69 .0023
Schirmer I test results (mm) 20.46 12.80 24.88 9.25 <.0001
Meniscus height (mm) 0.70 0.10 0.77 0.10 .0737
Rose bengal 0.50 0.98 0.38 0.71 .1563
Fluorescein 1.25 2.01 1.00 1.35 .5693

SD = standard deviation.


The distribution and the average number of D. folliculorum found in the lashes after oral ivermectin are shown in the Table 2 . We observed an overall statistical reduction of the absolute number of D. folliculorum found in the lashes after the treatment with oral ivermectin. 66.95% of the D. folliculorum was found in the inferior lid (temporal, 10.43%; center, 25.21%; nasal, 31.30%), and 33.04% was found in the superior lid (temporal, 5.21%; center, 14.78%; nasal, 13.04%).



TABLE 2

Average and Standard Deviation of the Absolute Number of Demodex folliculorum Found in the Superior and Inferior Lashes before and after Treatment with Systemic Ivermectin



























































































Area Before After P Value
Average SD Average SD
Superior lid
Temporal 0.25 0.68 0.04 0.20
Center 0.71 0.95 0.04 0.20
Nasal 0.63 0.77 0.13 0.34
Total 1.58 1.50 0.21 0.66 .0003
Inferior lid
Temporal 0.50 0.78 0.00 0.00
Center 1.21 0.93 0.08 0.28
Nasal 1.50 1.14 0.25 0.44
Total 3.21 2.17 0.33 0.64 <.0001
Total, superior plus inferior 4.79 3.09 0.54 1.22 <.0001

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Jan 16, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Clinical Treatment of Ocular Demodex folliculorumby Systemic Ivermectin
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