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The efficacy of tea tree face wash, 1, 2-Octanediol and microblepharoexfoliation in treating Demodex folliculorum blepharitis
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The efficacy of tea tree face wash, 1, 2-Octanediol and microblepharoexfoliation in treating Demodex folliculorum blepharitis ⁎
Orla Murphy , Veronica O’Dwyer, Aoife Lloyd-McKernan Dublin Institute of Technology, Ireland
A R T I C L E I N F O
A B S T R A C T
Keywords: Demodex folliculorum Blepharitis Treatment Tea tree face wash OcuSoft plus BlephExTM
Purpose: To compare the efficacy of Dr Organic Tea Tree Face Wash, OcuSoft Lids Scrub Plus and the BlephEx™ device at treating of Demodex folliculorum blepharitis. Methods: Eighty-six subjects (33 males/36 females) were enrolled in a randomised controlled interventional treatment study. Subjects completed a dry eye symptom questionnaire and were assessed for presence of Demodex folliculorum. Subjects were divided into three groups according to treatment: Dr Organic Tea Tree Face Wash (A) (n = 28), OcuSoft Lid Scrub Plus (B) (n = 30), or in-house lid scrub with the BlephEx™ device before nightly lid scrubs with OcuSoft Lid Scrub Plus (C) (n = 28). Subjects were advised to clean their eyelids nightly for four weeks. Each subject was re-assessed for symptoms and Demodex folliculorum blepharitis after two weeks and four weeks of treatment. Results: The quantity of Demodex folliculorum was significantly reduced after four weeks of treatment in all three groups (p < 0.05). Overall, there was no difference in efficacy between the three treatments (p > 0.1). Symptoms reported by subjects were significantly improved after two and four weeks of treatment (p < 0.05). Overall, there was no difference in efficacy between the three treatments to reduce symptoms after two or four weeks (p = 0.813 and p = 0.646 respectively). Conclusion: All three methods tested have shown good ability to reduce Demodex folliculorum quantity, improve subjective symptoms and help treat Demodex folliculorum blepharitis.
1. Introduction
has been reported to cause corneal neovascularisation, infiltration, opacities and scars [20,21]. DF use their claws to scrape at the internal walls of the lash follicles resulting in follicular distention, epithelial hyperplasia and reactive hyperkeratinisation which is visible as a translucent cuff at the base of the eyelash [22]. This finding is clinically known as cylindrical dandruff (CD) and is now considered a pathognomonic sign for the presence of DF [4]. To date, the majority of treatment studies to date have investigated treatment of Demodex skin infestation, with varying results [23–30]. It has emerged in recent years that tea tree oil (TTO) is quite effective at killing DF [31,32], and its use in treating DF blepharitis is growing [20,33–35]. Other studies have looked at the efficacy of acaricidal substances such as ivermectin and metronidazole with varying reports of success with each [36–38]. However the use of TTO, ivermectin and other systemic acaricidal drugs are not without their complications and may not be suitable for all patients. Alternative therapies need to be available for those not suitable, or in countries where the drug has not yet been licensed for human use. There are many products available marketed for the treatment of
Demodex folliculorum (DF) is a microscopic, host-specific ectoparasites that lives in the pilosebaceous units of humans. The mites are translucent and worm-like with a head, four pairs of legs, and a longer body tail [1,2]. Adult DF is approximately 0.4 mm in length [3,4], most frequently found on the eyelashes, and is associated with anterior blepharitis [2,5–7]. Demodex feeds on epidermal skin cells and sebum, and are therefore most commonly found in areas rich in sebaceous glands − cheeks, nose, chin and the periocular area [2,8]. The pathogenicity of the mites has long been debated [9–12]. While DF may begin as a saprophytic commensal organism that does not require intervention, it does appear to have pathogenic potential. It has been postulated that DF mites become pathogenic when the number of mites increases beyond a critical level (> 5 mites/cm2) [11], with higher densities associated with immunodeficiency [13]. Studies have also found DF and DB to be associated with blepharitis [2,5–7], chalazia [14–16], rosacea [17,18] and other dermatologic conditions [19]. In ocular rosacea, DF infestation
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Corresponding author. E-mail address: [email protected] (O. Murphy).
http://dx.doi.org/10.1016/j.clae.2017.10.012 Received 19 June 2017; Received in revised form 12 October 2017; Accepted 13 October 2017 1367-0484/ © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Murphy, O., Contact Lens and Anterior Eye (2017), http://dx.doi.org/10.1016/j.clae.2017.10.012
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Table 1 Lid Scrub Instructions. Step-by-step instructions provided to subjects for nightly lid scrubs at home.
Step 1: Step 2: Step 3:
Step 4: Step 5:
Group A (TTFW)
Group B (OLSP wipes) and Group C (BlephEx™)
Place a small amount of TTFW on a cotton pad Gently but thoroughly scrub the eyelid and lash margin in circular movements, ensuring to scrub along the base of the eyelashes Begin with the eyes closed to scrub along the top of the lashes. To scrub along the inner layer of lashes, look downwards to avoid contact with the cornea and gently pull the upper eyelid upwards. To scrub along the lower eyelashes, look upwards and gently pull down on the lower lid. Using a clean cotton pad, rinse the TTFW from the eyelids Repeat on other eye
Remove the OLSP wipe from its packet Gently but thoroughly scrub the eyelid and lash margin in circular movements, ensuring to scrub along the base of the eyelashes Begin with the eyes closed to scrub along the top of the lashes. To scrub along the inner layer of lashes, look downwards to avoid contact with the cornea and gently pull the upper eyelid upwards. To scrub along the lower eyelashes, look upwards and gently pull down on the lower lid. This is a leave-on formula, do not rinse until morning Repeat on other eye
blepharitis and dry eye, which seem to be low risk, first choice of treatments in many cases. However, it has been noted that many of these commercial products are available, without substantial evidence of efficacy, and further research in this area has been recommended [39]. The aim of the current study is to investigate the efficacy of three different treatment methods at reducing the quantity of DF. This study will provide evidence based results on the performance of commercial products available to patients and practitioners for the treatment of DF blepharitis in a clinical setting.
provide debridement and exfoliation at the lash margin. This treatment is referred to as microblepharoexfoliation [43]. 2.1. Examination All examinations were conducted by one optometrist, the author (OM). Subjects completed a modified version of the OSDI dry eye questionnaire. The OSDI questionnaire is graded on a 4-point Likert scale indicating frequency of the symptom in question: none of the time (0), some of the time (1), half of the time (2), most of the time (3), and all of the time (4). The total OSDI score is calculated using the following formula: total symptom number x 25/number of questions answered [44,45]. This creates a score on a scale of 0–100, with higher scores indicating increased severity of symptoms. The severity of symptoms were then graded from grade 0 (normal) to grade 3 (severe) according to OSDI guidelines. Lee et al. [46] modified the OSDI questionnaire by adding questions relating to blepharitis (itchy eyes and matter along the eyelid margin), in order to increase the questionnaires sensitivity to detect DF. Similar to Lee et al. [46] questions relating to itchy eyes and matter along the eyelid margin were added to the questionnaire used in the current study (validation paper submitted for review). Habitual visual acuity (LogMAR) was measured. Slit lamp examination was conducted to assess and grade presence of CD. All subjects were then assessed for the presence of DF. This involved examining one eyelash from each eyelid; first through manipulation of the eyelash, and then epilation and microscopic examination. Manipulation of the eyelashes involved rotation of the lash in clockwise and counter-clockwise directions using a sterile forceps, stimulating DF tails, if present, to emerge from the lash follicle. The lash was then epilated and examined under a microscope to count DF. Adult DF count was recorded using the modified Coston method [4]. Presence of DF was defined as: DF seen on lash rotation and/or one or more DF counted on microscopic examination.
2. Materials and methods This study was conducted under the Tenets of Helsinki Declaration of Human Studies [40] after approval by the Dublin Institute of Technology Research Ethics Committee. Written informed consent was obtained from all subjects prior to enrolment. Eighty-six subjects were recruited through the National Optometry Centre of Dublin Institute of Technology. All subjects were over 18 years of age. Subjects were excluded if they had ocular surgery in the past six months, or were undergoing current ophthalmic treatment. The subjects were divided into groups according to treatment:
• Group A: Dr Organic Tea Tree Face Wash (TTFW) (n = 28); • Group B: OcuSoft Lid Scrub Plus (OLSP) (n = 30); • Group C: BlephEx™ microblepharoexfoliation device (n = 28); Each subject chose a number from the list, which corresponded to the treatment assigned to the subject. The examiner was blind to the treatment throughout all stages of the study for group A and group B. The examiner performed the BlephEx™ treatment on subjects from group C and was therefore not blind to the treatment in this group. Dr Organic TTFW contains 38% terpinen-4-ol, the most active ingredient in tea tree shown to be effective at killing DF in a dose dependent manner [32]. The active ingredient in OLSP wipes is 1, 2-Octanediol; a substance which has been shown to have pediculicide potential [41]. BlephEx™ is a patented [42] hand-held device, developed for the treatment of ocular surface disorders including blepharitis. The apparatus consists of a hand-held electromechanical unit and a disposable micro-sponge inserted in the chuck that spins rapidly to
2.2. Lid scrubs routine The lid scrub routine is outlined in Table 1. In house microblepharoexfoliation was carried out on group C at the initial visit only. The procedure, as per manufacturer’s guidelines, was as seen in Table 2.
Table 2 In-house microblepharoexfoliation procedure with BlephEx™ as per manufacturer’s guidelines. Group C: BlephEx™ Microblepharoexfoliation procedure Step 1: Step 2: Step 3:
Step 4: Step 5:
Soak the sterile micro-sponge tip in cleaning solution (OcuSoft Lid Scrub Plus foam was used for this study) Once soaked, insert one tip into the BlephEx™ chuck Instruct the patient to lean their head back. Treat one eyelid at a time, using a new tip for each lid. For the upper eyelid; gently pull up on the upper eyelid and instruct the patient to look downwards. For the lower eyelid; gently pull down on the lower eyelid and instruct the patient to look upwards. To scrub; apply the spinning micro-sponge to the edge of the eyelid and lash line, and sweep from nasal to temporal and back again in a scrubbing motion for 20–30 s or until as much debris as possible is removed. After scrubbing with BlephEx™, clean the patient’s eyelids with saline to rinse off the formula.
2
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Table 3 Number of subjects with Demodex folliculorum and number of control subjects in each group.
Group A: Dr Organic TTFW Group B: OLSP wipes Group C: BlephEx™
Subjects with DF (n)
Control (n)
Total (n)
22 24 23
6 6 5
28 30 28
Table 5 Severity of symptoms and quantity of Demodex folliculorum in each group at baseline, two weeks, and four weeks. Severity of symptoms: Total modified OSDI number (mean ± std. dev). Quantity of Demodex folliculorum (mean and range). Group A Dr Organic TTFW
All subjects were seen for a check-up appointment at two weeks and again for a final check at four weeks 2.3. Statistical analysis Statistical analysis was performed using SPSS IBM (ver. 22.0). Oneway analysis of variance (ANOVA) was used to analyse between group data. Paired t-test was used to analyse within group data. Data between categorical variables was assessed using Chi-square analysis (X2). Spearman’s correlation co-efficient (rs) was used to assess continuous variables.
Eight-six subjects were recruited and divided into three groups according to treatment (Table 3). Subjects who did not have any DF were used as controls, therefore statistical analysis on quantity of DF was only applied to individuals found positive for DF. Overall the mean habitual LogMAR visual acuity improved posttreatment (LogMAR; 1.08 ± 0.26 at baseline, 1.12 ± 0.26 at two weeks, and 1.16 ± 0.26 at four weeks). The difference between baseline and two weeks, and baseline and four weeks was statistically significant (t-test; p = 0.005 and p = < 0.001). There was no statistically significant improvement in visual acuity between two and four weeks (t-test; p = 0.510). There was no significant difference in age between the treatment groups. However, there was a significant difference in age between the control subjects and subjects with DF in both group A and group B (Table 4). Throughout the study there was no significant difference in symptoms or quantity of DF between each treatment group. Results are for subjects with DF only (Table 5). The majority of subjects with DF were severely symptomatic: asymptomatic (n = 18), mild (n = 12), moderate (n = 11), and severe (n = 28). However, no statistically significant correlation was found between DF count and subjective symptom grade or modified OSDI score at baseline visit (K-W; p = 0.465 and rs; p = 0.536). As can be seen in Table 5; symptoms reduced progressively throughout the four weeks of treatment in each group. For all three treatment groups the reduction in symptoms between baseline and two weeks was significant (baseline to two weeks, t-test; A: p = 0.027, B: p = 0.001, C: p = 0.012). Subjects’ symptoms continued to improve after four weeks of treatment (baseline to four weeks, t-test; A: p = 0.010, B: p = 0.001, C: p = 0.001). However, the differences in symptoms
Subjects with DF Control KruskalWallis
Group C BlephEx™ (Yrs.)
ANOVA
49.6 ± 17.1
49.6 ± 16.9
49.86 ± 19.7
p = 0.998
30.0 ± 9.4 p = 0.008
33.2 ± 16.6 p = 0.013
38.80 ± 17.6 p = 0.207
p = 0.623
ANOVA
Symptoms (OSDI) Baseline 27.4 ± 16.7 Two weeks 18.3 ± 15.7 Four weeks 16.2 ± 15.20
28.6 ± 23.6 15.1 ± 17.2 13.6 ± 17.1
30.1 ± 19.8 17.4 ± 18.8 12.8 ± 12.8
p = 0.905 p = 0.813 p = 0.646
Quantity DF (count) Baseline 4.9 (0–21) Two weeks 2.2 (0–12) Four weeks 1.9 (0–8)
3.8 (0–11) 2.5 (0–17) 1.9 (0–7)
6.5 (1–25) 3.1 (0–13) 2.7 (0–9)
p = 0.220 p = 0.703 p = 0.498
4. Discussion
Table 4 Age of subjects with Demodex folliculorum and age of control subjects in each group. Group B OLSP wipes (Yrs.)
Group C BlephEx™
between week two and four were not significant (two weeks to four weeks, t-test; A: p = 0.412, B: p = 0.379, C: p = 0.052). Subjects with DF were more symptomatic than subjects in the control group. However, although a significant correlation was found (X2; p = 0.005), the authors feel it is not a valid comparison due to the difference in sample size between the two groups. In addition, subjects with DF were significantly older than control subjects, and the impact age has on dry eye symptoms has been well established [47]. This is a confounding factor, therefore it cannot be assumed that the increased symptoms among subjects with DF is as a result of DF alone. There was no statistically significant difference in control subjects’ symptoms at baseline between the three groups (ANOVA: p = 0.623). There was no statistically significant change in control subjects’ symptoms after treatment in each of the groups, except for group C after two weeks (baseline to two weeks, t-test; A: p = 0.212, B: p = 0.422, C: p = 0.033). After two weeks of treatment, symptoms were significantly lower in group C. However, OSDI score increased again between two and four weeks, resulting in no significant change overall (baseline to four weeks, t-test; A: p = 0.423, B: p = 0.200, C: p = 0.219). The reduction in numbers of DF after two weeks of treatment was significant for group A and group C but not group B (baseline to two weeks, t-test; A: p = 0.007, B: p = 0.057, C: p = 0.006). However, after four weeks of treatment the reduction in numbers of DF was significant in all three treatment groups (baseline to four weeks, t-test; A: p = 0.001, B: p = 0.005, C: p = 0.001). Similar to symptoms, the quantity of DF did continue to decrease from two weeks to four weeks, although the reduction in quantity between week two and week four was not significant (two weeks to four weeks, t-test; A: p = 0.595, B: p = 0.431, C: p = 0.430). At baseline DF count was marked zero for two subjects in group A, and three subjects in group B. A count of one or more DF was found for all subjects in group C at baseline. After two weeks of treatment DF count was reduced to zero in nine subjects in group A (range 0–12), ten subjects in group B (range 0–17), and six subjects in group C (range 0–13). After four weeks of treatment DF count was reduced to zero in nine subjects in group A (range 0–8), 11 subjects in group B (range 0–7), and nine subjects in group C (range 0–9).
3. Results
Group A Dr Organic TTFW (Yrs.)
Group B OLSP wipes
The pathogenicity of DF has been the subject of debate for some time [9–12]. Given that DF has been associated with blepharitis [2,5–7], chalazia [14–16], corneal disturbance [20,21] and an increase in symptoms [7,34,46,47], there is an argument for the pathogenic potential of the mite. It is now believed that DF presence is not the issue, but an increase in density of DF above normal levels (< 5 mites/ cm2) [11,13,48]. This study provides further evidence that DF may have pathogenic potential: although no significant correlation was found between DF count and modified OSDI, the majority of subjects with DF were symptomatic. Age is a possible influencer on this result, 3
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method of preventing establishment of an infestation of head lice was also investigated [53]. Results showed that routine, regular, thorough application of 1% 1, 2–Octanediol did provide effective protection from infestation. This study found that 0.5% 1, 2-Octanediol is effective at reducing DF count over a four week period. Complete elimination was not achieved, however the numbers were still reducing so potentially with continued treatment, a continued reduction in DF would occur. As the treatment does not appear to effect previously laid eggs, it is conceivable that these eggs hatched to give rise to the next generation. Complete coverage is required to be effective. If coverage by an applicant is incomplete some DF mites may survive to lay and hatch more DF, although with continuously diminishing numbers. However Burgess et al. [41] also stipulated that with 5% 1, 2 –Octanediol egg laying was completely inhibited and previously laid eggs did not mature to hatch. However, the study was carried out on head louse and not Demodex. While both are ectoparasites, no study could be found that compared the similarities and differences between the two. BlephEx™ was used as an adjunct therapy for Group C in this study. BlephEx™ lid scrub was given to subjects in office before they commenced treatment with OLSP wipes at home nightly, similar to the way 50% TTO lid scrubs were performed in office for participants in previous studies [20,33,34]. This was carried out to help reduce the bacterial load and kick start the cleaning process. The results of the current study found the greatest reduction in DF numbers and greatest improvement in symptoms in the BlephEx™ group. Even among the control subjects who had no DF, they reported a significant improvement in symptoms after 2 weeks. The authors’ postulate that this is as a result of the deep cleaning, exfoliation action of the BlephEx™, which leaves the eyelids feeling thoroughly cleaned and refreshed regardless of the presence or absence of ocular disease. One limitation of the current study is that the control subjects was a smaller and younger group than the subjects with DF (Table 3). As a result, the authors have not made comparisons between the two groups with regards to symptoms. Given the unequal sample sizes and the association between dry eye and increasing age, it was concluded that it would not be a valid comparison. To completely understand the relationship between DF infestation and symptoms, and the effect of treatment on those symptoms, future study cohorts should be age and sex – matched controlled. It should also be noted that in the current study, the quantity of DF among some subjects with DF pre-treatment was recorded as zero (Table 5). This occurred as a result of DF being visible on eyelash rotation but when the eyelash was epilated the DF remained in the follicle and were not removed with the eyelash. This occurred mainly in highly infested damaged follicles where the lashes were loose. As a result, an accurate account of DF quantity that reflects severity of infestation is difficult to achieve from eyelash epilation and microscopic counting alone. Mastrota [54] describes eyelash rotation as an alternative technique to eyelash epilation to confirm DF infestation. The authors believe that this is the cause for the apparent increase in range of DF in group B after two weeks although the average quantity of DF reduced. Further investigation is required into accurately diagnosing the severity of infestation and thus provide better information clinically to practitioners, in order to understand and know who and when to treat. With all treatment methods utilised in the current study, none fully eradicated DF in all subjects after four weeks. Potential reasons for this could be; the duration of treatment, frequency of application, subject compliance, and migration of DF. Subjects scrubbed their eyelids nightly for four weeks. This may potentially be too short a time frame to treat generations of DF. Treatment was only applied once a day, at night, and may be more effective if applied in the morning also. It is possible that subjects did not follow lid scrub procedure carefully which could impact efficacy of treatment. Finally DF can reside in other hair follicles on the face and body, not just the eyelashes. Therefore it is possible that mites may have migrated back to the eyelashes from other locations, and as a result total eradication of DF may not be possible
however treatment to reduce the numbers of DF significantly improved symptoms to a normal level; even though complete eradication was not achieved. The majority of control symptoms were asymptomatic, and treatment did not significantly reduce modified OSDI score. This further supports the theory that low numbers of DF are normal and not pathogenic and it could be argued that treatment can be considered successful when density DF is returned to normal levels. Guidelines available to practitioners (e.g. American Academy of Ophthalmology [49], and The College of Optometrists [50]) state that the level of evidence is low and the strength of recommendation is weak. Baby shampoo and cleansing pads are recommended but there is little evidence available that examines the efficacy of these treatments being administered to patients. In fact, it has recently been demonstrated that baby shampoo can have an adverse effect on the tear film [51]. In addition, Gao et al. (2005) discovered that the survival time of DF in 50% baby shampoo solution was > 150 min, and patients treated with baby shampoo lid scrubs for up to 350 days showed no significant change in DF quantity. Recently, TTO and ivermectin have emerged as the go-to-treatment options for Demodex blepharitis [20,31,33,34,36–38]. It has been found that terpinen-4-ol is the active ingredient in TTO effective at killing DF in a dose dependent manner [31,32]. Several studies have found that 50% TTO applied weekly is effective at reducing DF infestation [20,33,34]. Gao et al. (2012) discovered that even at as low a concentration as 5%, TTO is still effective at killing Demodex mites when applied twice a day. However, irritation after using TTO has been reported in previous studies [20,33,34,52]. Due to the potential toxic nature of TTO to the ocular surface, The College of Optometrists advised that application of TTO to the eyelids for the treatment of Demodex blepharitis should only be done by an “experienced practitioner” [50]. The current study looked at the efficacy of daily lid scrubs with TTFW for the treatment of DF blepharitis. The TTFW used in the current study had a 38% concentration of terpinen-4-ol and has shown to effectively reduce DF count over a 4 week period. For the purpose of the study, participants only scrubbed their eyelids, however, the face wash can be used on the entire face; theoretically giving the ability to reduce DF counts if present on the facial skin. Furthermore, if DF mites on the face are also being targeted, this reduces the risk of migration of mites back to the eyelashes again following topical treatment. Tea tree face wash can be applied at home as part of a routine facial cleaning regime, and does not require experienced practitioner application, thus reducing chair time and cost for the patient. Irritation however was still a factor even with the face wash which could impact patient compliance in the long run. Over-the-counter lid cleaning wipes have become available in recent years for the treatment of blepharitis, but little evidence is available as to their ability to treat the condition. Cliradex is a lid wipe with terpinen-4-ol, the active ingredient from TTO, which has shown promising results for the treatment of DF blepharitis [32]. OcuSoft Lid Scrub Plus is marketed as a product for moderate to severe blepharitis sufferers, with bacterial/Demodex involvement. Previous studies have demonstrated that a 5% solution of 1, 2-Octanediol, when left on for 8 h over night, is effective in eliminating an established head louse infestation with a cure rate of 80% after one use [41]. Observations from the same study showed that 1% 1, 2-octanediol solutions also killed lice but at a slower rate, probably disrupting the cuticular lipid of the lice, resulting in dehydration [41]. The effect of pediculicides is not always immediate and subsequently some micro-organisms may survive long enough to lay eggs subsequent to treatment. Burgess et al. [41] found that 5% 1, 2-Octanediol also inhibited headlice egg laying. Previously laid eggs however were unaffected by the chemical and could potentially survive to start a new infestation [41]. A 0.5% concentration of 1, 2-Octanediol is used in OLSP wipes to ensure the wipes are non-irritating yet still effective when used repeatedly for a period of time. Nonirritation allows a patient to use the wipes comfortably with good compliance over multiple uses. The use of 1% 1, 2–Octanediol as a 4
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Saleh, Evaluation of the efficacy of oral ivermectin in comparison with ivermectin-metronidazole combined therapy in the treatment of ocular and skin lesions of Demodex folliculorum, Int J Infect Dis 17 (2013) e343–e357, http://dx.doi.org/10.1016/j.ijid.2012.11.022. [39] S. Lindsley, E. Matsumura, E.K. Hatef, Interventions for chronic blepharitis, Cochrane Database Syst Rev 5 (2012), http://dx.doi.org/10.1002/14651858 CD005556. pub2. [40] World Medical Association, World medical association declaration of helsinki ethical principles for medical research involving human subjects, JAMA 310 (2013) 2191–2194. [41] I.F. Burgess, P.N. Lee, K. Kay, R. Jones, E.R. Brunton, 1, 2-Octanediol, a novel surfactant, for treating head louse infestation: identification of activity, formulation, and randomised, controlled trials, PLoS One 7 (2012) e35419, http://dx.doi. org/10.1371/journal.pone.0035419. [42] J.M. Rynerson, Method and device for treating an ocular disorder, (2012) US20140031845 A1 (Accessed 20 April 2017) https://www.google.com/patents/ US20140031845. [43] J.M. Rynerson, H.D. Perry, DEBS − a unification theory for dry eye and blepharitis, Clin Ophthalmol 10 (2016) 2455–2467, http://dx.doi.org/10.2147/OPTH. S114674. [44] R.M. Schiffman, M.D. Christianson, G. Jacobsen, J.D. Hirsch, B.L. Reis, L. MA, et al., Reliability and validity of the ocular surface disease index, arch, Ophthalmol 118 (2000) 615, http://dx.doi.org/10.1001/archopht.118.5.615. [45] J. Walt, Ocular Surface Disease Index (OSDI) Administration and Scoring Manual, (2004). [46] S.H. Lee, Y.S. Chun, J.H. Kim, E.S. Kim, J.C. Kim, The relationship between demodex and ocular discomfort, Investig Ophthalmol Vis Sci 51 (2010) 2906–2911. [47] A. Sędzikowska, M. Osęka, B. Grytner-Zięcina, Ocular symptoms reported by patients infested with Demodex mites, Acta Parasitol 61 (2016) 808–814. [48] S.G. Nicholls, C.L. Oakley, A. Tan, B.J. Vote, Demodex species in human ocular disease: new clinicopathological aspects, Int Ophthalmol 37 (2017) 303–312, http://dx.doi.org/10.1007/s10792-016-0249-9. [49] American academy of ophthalmology Cornea/External disease panel, Blepharitis, Prefer. Pract. Pattern® Guidel, (2013) https://www.aao.org/preferred-practicepattern/blepharitis-ppp. [50] The college of optometrists, blepharitis (Lid margin disease), Clin. Manag. Guidel,
using a local treatment. 5. Conclusion This study has shown that daily lid hygiene with both TTFW and OLSP are effective at reducing DF quantity and symptoms. However, inhouse microblepharoexfoliation helps to give a greater improvement in symptoms and kick-start a blepharitis cleaning regimen in patients affected with blepharitis. All three methods tested in this study have shown good ability to reduce DF count. The current study provides evidence based results for the use of commercial products available for the treatment of DF blepharitis in a clinical setting. Conflict of interest The following study was conducted as part of a self-funded postgraduate research degree. The materials used in the study were supplied by Scope Ophthalmics and Dr Organic Ltd. The authors do not have any financial interest in any of the products mentioned in this study. References [1] R.L. Breckenridge, Infestation of the skin with demodex folliculorum, Am J Clin Pathol 23 (1953) 348–352. [2] T. Coston, Demodex folliculorum blepharitis, Trans Am Ophthalmol Soc 65 (1967) 361–392. [3] N. Lacey, K. Kavanagh, S. Tseng, Under the lash: demodex mites in human diseases, Biochem (Lond) 31 (2009) 2–6. [4] Y.Y. Gao, M.A. Di Pascuale, W. Li, D.T.S. Liu, A. Baradaran-Rafii, A. Elizondo, et al., High prevalence of Demodex in eyelashes with cylindrical dandruff, Invest Ophthalmol Vis Sci 46 (2005) 3089–3094. [5] J. Liu, H. Sheha, S.C.G. Tseng, Pathogenic role of Demodex mites in blepharitis, Curr Opin Allergy Clin Immunol 10 (2010) 505–510. [6] D. Czepita, W. Kuźna-Grygiel, M. Czepita, A. Grobelny, Demodex folliculorum and Demodex brevis as a cause of chronic marginal blepharitis, Ann Acad Med Stetin 53 (2007) 63–67 (Accessed 1 September 2016), http://www.ncbi.nlm.nih.gov/ pubmed/18561612. [7] N. Kabataş, A.Ş. Doğan, E.U. Kabataş, M. Acar, T. Biçer, C. Gürdal, The effect of demodex infestation on blepharitis and the ocular symptoms, Eye Contact Lens 43 (2017) 64–67 (Accessed 6 April 2017), http://www.ncbi.nlm.nih.gov/pubmed/ 26783981. [8] T. Rufli, Y. Mumcuoglu, The hair follicle mites demodex folliculorum and demodex brevis: biology and medical importance, Dermatologica 162 (1981) 1–11. [9] N. Lacey, S. Ní Raghallaigh, F.C. Powell, Demodex mites–commensals, parasites or mutualistic organisms? Dermatology 222 (2011) 128–130. [10] W. Chen, G. Plewig, Are Demodex mites principal, conspirator, accomplice, witness or bystander in the cause of rosacea? Am J Clin Dermatol 16 (2015) 67–72, http:// dx.doi.org/10.1007/s40257-015-0115-y. [11] B. Baima, M. Sticherling, Demodicidosis revisited, Acta Derm Venereol 82 (2002) 3–6. [12] C.A. Elston, D.M. Elston, Demodex mites, Clin Dermatol 32 (2014) 739–743, http:// dx.doi.org/10.1016/j.clindermatol.2014.02.012. [13] F. Forton, M.-A. Germaux, T. Brasseur, A. De Liever, M. Laporte, C. Mathys, et al., Demodicosis and rosacea: epidemiology and significance in daily dermatologic practice, J Am Acad Dermatol 52 (2005) 74–87. [14] M.J. Schear, T. Milman, T. Steiner, C. Shih, I.J. Udell, A. Steiner, The association of demodex with chalazia: a histopathologic study of the eyelid, Ophthal Plast Reconstr Surg 32 (2015) 275–288, http://dx.doi.org/10.1097/IOP. 0000000000000500. [15] U. Guvendi Akcinar, E. Unal, M. Akpinar, Demodex spp. infestation associated with treatment-Resistant chalazia and folliculitis, Turkish J Parasitol 40 (2017) 208–210, http://dx.doi.org/10.5152/tpd.2016.4869. [16] L. Liang, X. Ding, S.C.G. Tseng, High prevalence of demodex brevis infestation in chalazia, Am J Ophthalmol (2013), http://dx.doi.org/10.1016/j.ajo.2013.09.031. [17] E. Bonnar, P. Eustace, F.C. Powell, The Demodex mite population in rosacea, J Am Acad Dermatol 28 (1993) 443–448, http://dx.doi.org/10.1016/0190-9622(93) 70065-2. [18] S. Jarmuda, N. O’Reilly, R. Zaba, O. Jakubowicz, A. Szkaradkiewicz, K. Kavanagh, Potential role of Demodex mites and bacteria in the induction of rosacea, J Med Microbiol 61 (2012) 1504–1510. [19] Y. Karincaoglu, N. Bayram, O. Aycan, M. Esrefoglu, The clinical importance of Demodex folliculorum presenting with nonspecific facial signs and symptoms, J Dermatol 31 (2004) 618–626, http://dx.doi.org/10.1111/j. 1346–8138.2004. tb00567. x. [20] A. Kheirkhah, V. Casas, W. Li, V.K. Raju, S.C.G. Tseng, Corneal manifestations of ocular demodex infestation, Am J Ophthalmol 143 (2007) 743–749. [21] B. Kamoun, M. Fourati, J. Feki, M. Mlik, F. Karray, A. Trigui, et al., [Blepharitis due to Demodex: myth or reality?], J Fr d’ophtalmologie 22 (1999) 525–537 (Accessed
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dx.doi.org/10.1097/ICO.0b013e31820ce56c. [53] I.F. Burgess, E.R. Brunton, R. French, N.A. Burgess, Prevention of head louse infestation: a randomised, double-blind, cross-over study of a novel concept product, 1% 1, 2-octanediol spray versus placebo, BMJ Open 4 (2014), http://dx.doi.org/10. 1136/bmjopen-2013-004634 e004634. [54] K.M. Mastrota, Method to identify demodex in the eyelash follicle without epilation, Optom Vis Sci 90 (2013) e172–e174, http://dx.doi.org/10.1097/OPX. 0b013e318294c2c0.
(2016) (Accessed 12 April 2017), https://www.college-optometrists.org/guidance/ clinical-management-guidelines/blepharitis-lid-margin-disease.html. [51] J. Craig, J. Sung, M. Wang, I. Cheung, T. Sherwin, S. Ismail, Commercial lid cleanser outperforms baby shampoo for management of blepharitis in randomized, doublemasked clinical trial, Invest Ophthalmol Vis Sci 58 (2017) Meeting abstract (Program Number:2247) http://iovs.arvojournals.org/article.aspx?articleid= 2639901&resultClick=1. [52] Y.Y. Gao, D.L. Xu, L.J. Huang, R. Wang, S.C.G. Tseng, Treatment of ocular itching associated with ocular demodicosis by 5%, Tea Tree Oil Ointment (2012), http://
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The efficacy of tea tree face wash, 1, 2-Octanediol and microblepharoexfoliation in treating Demodex folliculorum blepharitis ⁎
Orla Murphy , Veronica O’Dwyer, Aoife Lloyd-McKernan Dublin Institute of Technology, Ireland
A R T I C L E I N F O
A B S T R A C T
Keywords: Demodex folliculorum Blepharitis Treatment Tea tree face wash OcuSoft plus BlephExTM
Purpose: To compare the efficacy of Dr Organic Tea Tree Face Wash, OcuSoft Lids Scrub Plus and the BlephEx™ device at treating of Demodex folliculorum blepharitis. Methods: Eighty-six subjects (33 males/36 females) were enrolled in a randomised controlled interventional treatment study. Subjects completed a dry eye symptom questionnaire and were assessed for presence of Demodex folliculorum. Subjects were divided into three groups according to treatment: Dr Organic Tea Tree Face Wash (A) (n = 28), OcuSoft Lid Scrub Plus (B) (n = 30), or in-house lid scrub with the BlephEx™ device before nightly lid scrubs with OcuSoft Lid Scrub Plus (C) (n = 28). Subjects were advised to clean their eyelids nightly for four weeks. Each subject was re-assessed for symptoms and Demodex folliculorum blepharitis after two weeks and four weeks of treatment. Results: The quantity of Demodex folliculorum was significantly reduced after four weeks of treatment in all three groups (p < 0.05). Overall, there was no difference in efficacy between the three treatments (p > 0.1). Symptoms reported by subjects were significantly improved after two and four weeks of treatment (p < 0.05). Overall, there was no difference in efficacy between the three treatments to reduce symptoms after two or four weeks (p = 0.813 and p = 0.646 respectively). Conclusion: All three methods tested have shown good ability to reduce Demodex folliculorum quantity, improve subjective symptoms and help treat Demodex folliculorum blepharitis.
1. Introduction
has been reported to cause corneal neovascularisation, infiltration, opacities and scars [20,21]. DF use their claws to scrape at the internal walls of the lash follicles resulting in follicular distention, epithelial hyperplasia and reactive hyperkeratinisation which is visible as a translucent cuff at the base of the eyelash [22]. This finding is clinically known as cylindrical dandruff (CD) and is now considered a pathognomonic sign for the presence of DF [4]. To date, the majority of treatment studies to date have investigated treatment of Demodex skin infestation, with varying results [23–30]. It has emerged in recent years that tea tree oil (TTO) is quite effective at killing DF [31,32], and its use in treating DF blepharitis is growing [20,33–35]. Other studies have looked at the efficacy of acaricidal substances such as ivermectin and metronidazole with varying reports of success with each [36–38]. However the use of TTO, ivermectin and other systemic acaricidal drugs are not without their complications and may not be suitable for all patients. Alternative therapies need to be available for those not suitable, or in countries where the drug has not yet been licensed for human use. There are many products available marketed for the treatment of
Demodex folliculorum (DF) is a microscopic, host-specific ectoparasites that lives in the pilosebaceous units of humans. The mites are translucent and worm-like with a head, four pairs of legs, and a longer body tail [1,2]. Adult DF is approximately 0.4 mm in length [3,4], most frequently found on the eyelashes, and is associated with anterior blepharitis [2,5–7]. Demodex feeds on epidermal skin cells and sebum, and are therefore most commonly found in areas rich in sebaceous glands − cheeks, nose, chin and the periocular area [2,8]. The pathogenicity of the mites has long been debated [9–12]. While DF may begin as a saprophytic commensal organism that does not require intervention, it does appear to have pathogenic potential. It has been postulated that DF mites become pathogenic when the number of mites increases beyond a critical level (> 5 mites/cm2) [11], with higher densities associated with immunodeficiency [13]. Studies have also found DF and DB to be associated with blepharitis [2,5–7], chalazia [14–16], rosacea [17,18] and other dermatologic conditions [19]. In ocular rosacea, DF infestation
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Corresponding author. E-mail address: [email protected] (O. Murphy).
http://dx.doi.org/10.1016/j.clae.2017.10.012 Received 19 June 2017; Received in revised form 12 October 2017; Accepted 13 October 2017 1367-0484/ © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Murphy, O., Contact Lens and Anterior Eye (2017), http://dx.doi.org/10.1016/j.clae.2017.10.012
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Table 1 Lid Scrub Instructions. Step-by-step instructions provided to subjects for nightly lid scrubs at home.
Step 1: Step 2: Step 3:
Step 4: Step 5:
Group A (TTFW)
Group B (OLSP wipes) and Group C (BlephEx™)
Place a small amount of TTFW on a cotton pad Gently but thoroughly scrub the eyelid and lash margin in circular movements, ensuring to scrub along the base of the eyelashes Begin with the eyes closed to scrub along the top of the lashes. To scrub along the inner layer of lashes, look downwards to avoid contact with the cornea and gently pull the upper eyelid upwards. To scrub along the lower eyelashes, look upwards and gently pull down on the lower lid. Using a clean cotton pad, rinse the TTFW from the eyelids Repeat on other eye
Remove the OLSP wipe from its packet Gently but thoroughly scrub the eyelid and lash margin in circular movements, ensuring to scrub along the base of the eyelashes Begin with the eyes closed to scrub along the top of the lashes. To scrub along the inner layer of lashes, look downwards to avoid contact with the cornea and gently pull the upper eyelid upwards. To scrub along the lower eyelashes, look upwards and gently pull down on the lower lid. This is a leave-on formula, do not rinse until morning Repeat on other eye
blepharitis and dry eye, which seem to be low risk, first choice of treatments in many cases. However, it has been noted that many of these commercial products are available, without substantial evidence of efficacy, and further research in this area has been recommended [39]. The aim of the current study is to investigate the efficacy of three different treatment methods at reducing the quantity of DF. This study will provide evidence based results on the performance of commercial products available to patients and practitioners for the treatment of DF blepharitis in a clinical setting.
provide debridement and exfoliation at the lash margin. This treatment is referred to as microblepharoexfoliation [43]. 2.1. Examination All examinations were conducted by one optometrist, the author (OM). Subjects completed a modified version of the OSDI dry eye questionnaire. The OSDI questionnaire is graded on a 4-point Likert scale indicating frequency of the symptom in question: none of the time (0), some of the time (1), half of the time (2), most of the time (3), and all of the time (4). The total OSDI score is calculated using the following formula: total symptom number x 25/number of questions answered [44,45]. This creates a score on a scale of 0–100, with higher scores indicating increased severity of symptoms. The severity of symptoms were then graded from grade 0 (normal) to grade 3 (severe) according to OSDI guidelines. Lee et al. [46] modified the OSDI questionnaire by adding questions relating to blepharitis (itchy eyes and matter along the eyelid margin), in order to increase the questionnaires sensitivity to detect DF. Similar to Lee et al. [46] questions relating to itchy eyes and matter along the eyelid margin were added to the questionnaire used in the current study (validation paper submitted for review). Habitual visual acuity (LogMAR) was measured. Slit lamp examination was conducted to assess and grade presence of CD. All subjects were then assessed for the presence of DF. This involved examining one eyelash from each eyelid; first through manipulation of the eyelash, and then epilation and microscopic examination. Manipulation of the eyelashes involved rotation of the lash in clockwise and counter-clockwise directions using a sterile forceps, stimulating DF tails, if present, to emerge from the lash follicle. The lash was then epilated and examined under a microscope to count DF. Adult DF count was recorded using the modified Coston method [4]. Presence of DF was defined as: DF seen on lash rotation and/or one or more DF counted on microscopic examination.
2. Materials and methods This study was conducted under the Tenets of Helsinki Declaration of Human Studies [40] after approval by the Dublin Institute of Technology Research Ethics Committee. Written informed consent was obtained from all subjects prior to enrolment. Eighty-six subjects were recruited through the National Optometry Centre of Dublin Institute of Technology. All subjects were over 18 years of age. Subjects were excluded if they had ocular surgery in the past six months, or were undergoing current ophthalmic treatment. The subjects were divided into groups according to treatment:
• Group A: Dr Organic Tea Tree Face Wash (TTFW) (n = 28); • Group B: OcuSoft Lid Scrub Plus (OLSP) (n = 30); • Group C: BlephEx™ microblepharoexfoliation device (n = 28); Each subject chose a number from the list, which corresponded to the treatment assigned to the subject. The examiner was blind to the treatment throughout all stages of the study for group A and group B. The examiner performed the BlephEx™ treatment on subjects from group C and was therefore not blind to the treatment in this group. Dr Organic TTFW contains 38% terpinen-4-ol, the most active ingredient in tea tree shown to be effective at killing DF in a dose dependent manner [32]. The active ingredient in OLSP wipes is 1, 2-Octanediol; a substance which has been shown to have pediculicide potential [41]. BlephEx™ is a patented [42] hand-held device, developed for the treatment of ocular surface disorders including blepharitis. The apparatus consists of a hand-held electromechanical unit and a disposable micro-sponge inserted in the chuck that spins rapidly to
2.2. Lid scrubs routine The lid scrub routine is outlined in Table 1. In house microblepharoexfoliation was carried out on group C at the initial visit only. The procedure, as per manufacturer’s guidelines, was as seen in Table 2.
Table 2 In-house microblepharoexfoliation procedure with BlephEx™ as per manufacturer’s guidelines. Group C: BlephEx™ Microblepharoexfoliation procedure Step 1: Step 2: Step 3:
Step 4: Step 5:
Soak the sterile micro-sponge tip in cleaning solution (OcuSoft Lid Scrub Plus foam was used for this study) Once soaked, insert one tip into the BlephEx™ chuck Instruct the patient to lean their head back. Treat one eyelid at a time, using a new tip for each lid. For the upper eyelid; gently pull up on the upper eyelid and instruct the patient to look downwards. For the lower eyelid; gently pull down on the lower eyelid and instruct the patient to look upwards. To scrub; apply the spinning micro-sponge to the edge of the eyelid and lash line, and sweep from nasal to temporal and back again in a scrubbing motion for 20–30 s or until as much debris as possible is removed. After scrubbing with BlephEx™, clean the patient’s eyelids with saline to rinse off the formula.
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Table 3 Number of subjects with Demodex folliculorum and number of control subjects in each group.
Group A: Dr Organic TTFW Group B: OLSP wipes Group C: BlephEx™
Subjects with DF (n)
Control (n)
Total (n)
22 24 23
6 6 5
28 30 28
Table 5 Severity of symptoms and quantity of Demodex folliculorum in each group at baseline, two weeks, and four weeks. Severity of symptoms: Total modified OSDI number (mean ± std. dev). Quantity of Demodex folliculorum (mean and range). Group A Dr Organic TTFW
All subjects were seen for a check-up appointment at two weeks and again for a final check at four weeks 2.3. Statistical analysis Statistical analysis was performed using SPSS IBM (ver. 22.0). Oneway analysis of variance (ANOVA) was used to analyse between group data. Paired t-test was used to analyse within group data. Data between categorical variables was assessed using Chi-square analysis (X2). Spearman’s correlation co-efficient (rs) was used to assess continuous variables.
Eight-six subjects were recruited and divided into three groups according to treatment (Table 3). Subjects who did not have any DF were used as controls, therefore statistical analysis on quantity of DF was only applied to individuals found positive for DF. Overall the mean habitual LogMAR visual acuity improved posttreatment (LogMAR; 1.08 ± 0.26 at baseline, 1.12 ± 0.26 at two weeks, and 1.16 ± 0.26 at four weeks). The difference between baseline and two weeks, and baseline and four weeks was statistically significant (t-test; p = 0.005 and p = < 0.001). There was no statistically significant improvement in visual acuity between two and four weeks (t-test; p = 0.510). There was no significant difference in age between the treatment groups. However, there was a significant difference in age between the control subjects and subjects with DF in both group A and group B (Table 4). Throughout the study there was no significant difference in symptoms or quantity of DF between each treatment group. Results are for subjects with DF only (Table 5). The majority of subjects with DF were severely symptomatic: asymptomatic (n = 18), mild (n = 12), moderate (n = 11), and severe (n = 28). However, no statistically significant correlation was found between DF count and subjective symptom grade or modified OSDI score at baseline visit (K-W; p = 0.465 and rs; p = 0.536). As can be seen in Table 5; symptoms reduced progressively throughout the four weeks of treatment in each group. For all three treatment groups the reduction in symptoms between baseline and two weeks was significant (baseline to two weeks, t-test; A: p = 0.027, B: p = 0.001, C: p = 0.012). Subjects’ symptoms continued to improve after four weeks of treatment (baseline to four weeks, t-test; A: p = 0.010, B: p = 0.001, C: p = 0.001). However, the differences in symptoms
Subjects with DF Control KruskalWallis
Group C BlephEx™ (Yrs.)
ANOVA
49.6 ± 17.1
49.6 ± 16.9
49.86 ± 19.7
p = 0.998
30.0 ± 9.4 p = 0.008
33.2 ± 16.6 p = 0.013
38.80 ± 17.6 p = 0.207
p = 0.623
ANOVA
Symptoms (OSDI) Baseline 27.4 ± 16.7 Two weeks 18.3 ± 15.7 Four weeks 16.2 ± 15.20
28.6 ± 23.6 15.1 ± 17.2 13.6 ± 17.1
30.1 ± 19.8 17.4 ± 18.8 12.8 ± 12.8
p = 0.905 p = 0.813 p = 0.646
Quantity DF (count) Baseline 4.9 (0–21) Two weeks 2.2 (0–12) Four weeks 1.9 (0–8)
3.8 (0–11) 2.5 (0–17) 1.9 (0–7)
6.5 (1–25) 3.1 (0–13) 2.7 (0–9)
p = 0.220 p = 0.703 p = 0.498
4. Discussion
Table 4 Age of subjects with Demodex folliculorum and age of control subjects in each group. Group B OLSP wipes (Yrs.)
Group C BlephEx™
between week two and four were not significant (two weeks to four weeks, t-test; A: p = 0.412, B: p = 0.379, C: p = 0.052). Subjects with DF were more symptomatic than subjects in the control group. However, although a significant correlation was found (X2; p = 0.005), the authors feel it is not a valid comparison due to the difference in sample size between the two groups. In addition, subjects with DF were significantly older than control subjects, and the impact age has on dry eye symptoms has been well established [47]. This is a confounding factor, therefore it cannot be assumed that the increased symptoms among subjects with DF is as a result of DF alone. There was no statistically significant difference in control subjects’ symptoms at baseline between the three groups (ANOVA: p = 0.623). There was no statistically significant change in control subjects’ symptoms after treatment in each of the groups, except for group C after two weeks (baseline to two weeks, t-test; A: p = 0.212, B: p = 0.422, C: p = 0.033). After two weeks of treatment, symptoms were significantly lower in group C. However, OSDI score increased again between two and four weeks, resulting in no significant change overall (baseline to four weeks, t-test; A: p = 0.423, B: p = 0.200, C: p = 0.219). The reduction in numbers of DF after two weeks of treatment was significant for group A and group C but not group B (baseline to two weeks, t-test; A: p = 0.007, B: p = 0.057, C: p = 0.006). However, after four weeks of treatment the reduction in numbers of DF was significant in all three treatment groups (baseline to four weeks, t-test; A: p = 0.001, B: p = 0.005, C: p = 0.001). Similar to symptoms, the quantity of DF did continue to decrease from two weeks to four weeks, although the reduction in quantity between week two and week four was not significant (two weeks to four weeks, t-test; A: p = 0.595, B: p = 0.431, C: p = 0.430). At baseline DF count was marked zero for two subjects in group A, and three subjects in group B. A count of one or more DF was found for all subjects in group C at baseline. After two weeks of treatment DF count was reduced to zero in nine subjects in group A (range 0–12), ten subjects in group B (range 0–17), and six subjects in group C (range 0–13). After four weeks of treatment DF count was reduced to zero in nine subjects in group A (range 0–8), 11 subjects in group B (range 0–7), and nine subjects in group C (range 0–9).
3. Results
Group A Dr Organic TTFW (Yrs.)
Group B OLSP wipes
The pathogenicity of DF has been the subject of debate for some time [9–12]. Given that DF has been associated with blepharitis [2,5–7], chalazia [14–16], corneal disturbance [20,21] and an increase in symptoms [7,34,46,47], there is an argument for the pathogenic potential of the mite. It is now believed that DF presence is not the issue, but an increase in density of DF above normal levels (< 5 mites/ cm2) [11,13,48]. This study provides further evidence that DF may have pathogenic potential: although no significant correlation was found between DF count and modified OSDI, the majority of subjects with DF were symptomatic. Age is a possible influencer on this result, 3
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method of preventing establishment of an infestation of head lice was also investigated [53]. Results showed that routine, regular, thorough application of 1% 1, 2–Octanediol did provide effective protection from infestation. This study found that 0.5% 1, 2-Octanediol is effective at reducing DF count over a four week period. Complete elimination was not achieved, however the numbers were still reducing so potentially with continued treatment, a continued reduction in DF would occur. As the treatment does not appear to effect previously laid eggs, it is conceivable that these eggs hatched to give rise to the next generation. Complete coverage is required to be effective. If coverage by an applicant is incomplete some DF mites may survive to lay and hatch more DF, although with continuously diminishing numbers. However Burgess et al. [41] also stipulated that with 5% 1, 2 –Octanediol egg laying was completely inhibited and previously laid eggs did not mature to hatch. However, the study was carried out on head louse and not Demodex. While both are ectoparasites, no study could be found that compared the similarities and differences between the two. BlephEx™ was used as an adjunct therapy for Group C in this study. BlephEx™ lid scrub was given to subjects in office before they commenced treatment with OLSP wipes at home nightly, similar to the way 50% TTO lid scrubs were performed in office for participants in previous studies [20,33,34]. This was carried out to help reduce the bacterial load and kick start the cleaning process. The results of the current study found the greatest reduction in DF numbers and greatest improvement in symptoms in the BlephEx™ group. Even among the control subjects who had no DF, they reported a significant improvement in symptoms after 2 weeks. The authors’ postulate that this is as a result of the deep cleaning, exfoliation action of the BlephEx™, which leaves the eyelids feeling thoroughly cleaned and refreshed regardless of the presence or absence of ocular disease. One limitation of the current study is that the control subjects was a smaller and younger group than the subjects with DF (Table 3). As a result, the authors have not made comparisons between the two groups with regards to symptoms. Given the unequal sample sizes and the association between dry eye and increasing age, it was concluded that it would not be a valid comparison. To completely understand the relationship between DF infestation and symptoms, and the effect of treatment on those symptoms, future study cohorts should be age and sex – matched controlled. It should also be noted that in the current study, the quantity of DF among some subjects with DF pre-treatment was recorded as zero (Table 5). This occurred as a result of DF being visible on eyelash rotation but when the eyelash was epilated the DF remained in the follicle and were not removed with the eyelash. This occurred mainly in highly infested damaged follicles where the lashes were loose. As a result, an accurate account of DF quantity that reflects severity of infestation is difficult to achieve from eyelash epilation and microscopic counting alone. Mastrota [54] describes eyelash rotation as an alternative technique to eyelash epilation to confirm DF infestation. The authors believe that this is the cause for the apparent increase in range of DF in group B after two weeks although the average quantity of DF reduced. Further investigation is required into accurately diagnosing the severity of infestation and thus provide better information clinically to practitioners, in order to understand and know who and when to treat. With all treatment methods utilised in the current study, none fully eradicated DF in all subjects after four weeks. Potential reasons for this could be; the duration of treatment, frequency of application, subject compliance, and migration of DF. Subjects scrubbed their eyelids nightly for four weeks. This may potentially be too short a time frame to treat generations of DF. Treatment was only applied once a day, at night, and may be more effective if applied in the morning also. It is possible that subjects did not follow lid scrub procedure carefully which could impact efficacy of treatment. Finally DF can reside in other hair follicles on the face and body, not just the eyelashes. Therefore it is possible that mites may have migrated back to the eyelashes from other locations, and as a result total eradication of DF may not be possible
however treatment to reduce the numbers of DF significantly improved symptoms to a normal level; even though complete eradication was not achieved. The majority of control symptoms were asymptomatic, and treatment did not significantly reduce modified OSDI score. This further supports the theory that low numbers of DF are normal and not pathogenic and it could be argued that treatment can be considered successful when density DF is returned to normal levels. Guidelines available to practitioners (e.g. American Academy of Ophthalmology [49], and The College of Optometrists [50]) state that the level of evidence is low and the strength of recommendation is weak. Baby shampoo and cleansing pads are recommended but there is little evidence available that examines the efficacy of these treatments being administered to patients. In fact, it has recently been demonstrated that baby shampoo can have an adverse effect on the tear film [51]. In addition, Gao et al. (2005) discovered that the survival time of DF in 50% baby shampoo solution was > 150 min, and patients treated with baby shampoo lid scrubs for up to 350 days showed no significant change in DF quantity. Recently, TTO and ivermectin have emerged as the go-to-treatment options for Demodex blepharitis [20,31,33,34,36–38]. It has been found that terpinen-4-ol is the active ingredient in TTO effective at killing DF in a dose dependent manner [31,32]. Several studies have found that 50% TTO applied weekly is effective at reducing DF infestation [20,33,34]. Gao et al. (2012) discovered that even at as low a concentration as 5%, TTO is still effective at killing Demodex mites when applied twice a day. However, irritation after using TTO has been reported in previous studies [20,33,34,52]. Due to the potential toxic nature of TTO to the ocular surface, The College of Optometrists advised that application of TTO to the eyelids for the treatment of Demodex blepharitis should only be done by an “experienced practitioner” [50]. The current study looked at the efficacy of daily lid scrubs with TTFW for the treatment of DF blepharitis. The TTFW used in the current study had a 38% concentration of terpinen-4-ol and has shown to effectively reduce DF count over a 4 week period. For the purpose of the study, participants only scrubbed their eyelids, however, the face wash can be used on the entire face; theoretically giving the ability to reduce DF counts if present on the facial skin. Furthermore, if DF mites on the face are also being targeted, this reduces the risk of migration of mites back to the eyelashes again following topical treatment. Tea tree face wash can be applied at home as part of a routine facial cleaning regime, and does not require experienced practitioner application, thus reducing chair time and cost for the patient. Irritation however was still a factor even with the face wash which could impact patient compliance in the long run. Over-the-counter lid cleaning wipes have become available in recent years for the treatment of blepharitis, but little evidence is available as to their ability to treat the condition. Cliradex is a lid wipe with terpinen-4-ol, the active ingredient from TTO, which has shown promising results for the treatment of DF blepharitis [32]. OcuSoft Lid Scrub Plus is marketed as a product for moderate to severe blepharitis sufferers, with bacterial/Demodex involvement. Previous studies have demonstrated that a 5% solution of 1, 2-Octanediol, when left on for 8 h over night, is effective in eliminating an established head louse infestation with a cure rate of 80% after one use [41]. Observations from the same study showed that 1% 1, 2-octanediol solutions also killed lice but at a slower rate, probably disrupting the cuticular lipid of the lice, resulting in dehydration [41]. The effect of pediculicides is not always immediate and subsequently some micro-organisms may survive long enough to lay eggs subsequent to treatment. Burgess et al. [41] found that 5% 1, 2-Octanediol also inhibited headlice egg laying. Previously laid eggs however were unaffected by the chemical and could potentially survive to start a new infestation [41]. A 0.5% concentration of 1, 2-Octanediol is used in OLSP wipes to ensure the wipes are non-irritating yet still effective when used repeatedly for a period of time. Nonirritation allows a patient to use the wipes comfortably with good compliance over multiple uses. The use of 1% 1, 2–Octanediol as a 4
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using a local treatment. 5. Conclusion This study has shown that daily lid hygiene with both TTFW and OLSP are effective at reducing DF quantity and symptoms. However, inhouse microblepharoexfoliation helps to give a greater improvement in symptoms and kick-start a blepharitis cleaning regimen in patients affected with blepharitis. All three methods tested in this study have shown good ability to reduce DF count. The current study provides evidence based results for the use of commercial products available for the treatment of DF blepharitis in a clinical setting. Conflict of interest The following study was conducted as part of a self-funded postgraduate research degree. The materials used in the study were supplied by Scope Ophthalmics and Dr Organic Ltd. The authors do not have any financial interest in any of the products mentioned in this study. References [1] R.L. Breckenridge, Infestation of the skin with demodex folliculorum, Am J Clin Pathol 23 (1953) 348–352. [2] T. Coston, Demodex folliculorum blepharitis, Trans Am Ophthalmol Soc 65 (1967) 361–392. [3] N. Lacey, K. Kavanagh, S. Tseng, Under the lash: demodex mites in human diseases, Biochem (Lond) 31 (2009) 2–6. [4] Y.Y. Gao, M.A. Di Pascuale, W. Li, D.T.S. Liu, A. Baradaran-Rafii, A. Elizondo, et al., High prevalence of Demodex in eyelashes with cylindrical dandruff, Invest Ophthalmol Vis Sci 46 (2005) 3089–3094. [5] J. Liu, H. Sheha, S.C.G. Tseng, Pathogenic role of Demodex mites in blepharitis, Curr Opin Allergy Clin Immunol 10 (2010) 505–510. [6] D. Czepita, W. Kuźna-Grygiel, M. Czepita, A. Grobelny, Demodex folliculorum and Demodex brevis as a cause of chronic marginal blepharitis, Ann Acad Med Stetin 53 (2007) 63–67 (Accessed 1 September 2016), http://www.ncbi.nlm.nih.gov/ pubmed/18561612. [7] N. Kabataş, A.Ş. Doğan, E.U. Kabataş, M. Acar, T. Biçer, C. Gürdal, The effect of demodex infestation on blepharitis and the ocular symptoms, Eye Contact Lens 43 (2017) 64–67 (Accessed 6 April 2017), http://www.ncbi.nlm.nih.gov/pubmed/ 26783981. [8] T. Rufli, Y. Mumcuoglu, The hair follicle mites demodex folliculorum and demodex brevis: biology and medical importance, Dermatologica 162 (1981) 1–11. [9] N. Lacey, S. Ní Raghallaigh, F.C. Powell, Demodex mites–commensals, parasites or mutualistic organisms? Dermatology 222 (2011) 128–130. [10] W. Chen, G. Plewig, Are Demodex mites principal, conspirator, accomplice, witness or bystander in the cause of rosacea? Am J Clin Dermatol 16 (2015) 67–72, http:// dx.doi.org/10.1007/s40257-015-0115-y. [11] B. Baima, M. Sticherling, Demodicidosis revisited, Acta Derm Venereol 82 (2002) 3–6. [12] C.A. Elston, D.M. Elston, Demodex mites, Clin Dermatol 32 (2014) 739–743, http:// dx.doi.org/10.1016/j.clindermatol.2014.02.012. [13] F. Forton, M.-A. Germaux, T. Brasseur, A. De Liever, M. Laporte, C. Mathys, et al., Demodicosis and rosacea: epidemiology and significance in daily dermatologic practice, J Am Acad Dermatol 52 (2005) 74–87. [14] M.J. Schear, T. Milman, T. Steiner, C. Shih, I.J. Udell, A. Steiner, The association of demodex with chalazia: a histopathologic study of the eyelid, Ophthal Plast Reconstr Surg 32 (2015) 275–288, http://dx.doi.org/10.1097/IOP. 0000000000000500. [15] U. Guvendi Akcinar, E. Unal, M. Akpinar, Demodex spp. infestation associated with treatment-Resistant chalazia and folliculitis, Turkish J Parasitol 40 (2017) 208–210, http://dx.doi.org/10.5152/tpd.2016.4869. [16] L. Liang, X. Ding, S.C.G. Tseng, High prevalence of demodex brevis infestation in chalazia, Am J Ophthalmol (2013), http://dx.doi.org/10.1016/j.ajo.2013.09.031. [17] E. Bonnar, P. Eustace, F.C. Powell, The Demodex mite population in rosacea, J Am Acad Dermatol 28 (1993) 443–448, http://dx.doi.org/10.1016/0190-9622(93) 70065-2. [18] S. Jarmuda, N. O’Reilly, R. Zaba, O. Jakubowicz, A. Szkaradkiewicz, K. Kavanagh, Potential role of Demodex mites and bacteria in the induction of rosacea, J Med Microbiol 61 (2012) 1504–1510. [19] Y. Karincaoglu, N. Bayram, O. Aycan, M. Esrefoglu, The clinical importance of Demodex folliculorum presenting with nonspecific facial signs and symptoms, J Dermatol 31 (2004) 618–626, http://dx.doi.org/10.1111/j. 1346–8138.2004. tb00567. x. [20] A. Kheirkhah, V. Casas, W. Li, V.K. Raju, S.C.G. Tseng, Corneal manifestations of ocular demodex infestation, Am J Ophthalmol 143 (2007) 743–749. [21] B. Kamoun, M. Fourati, J. Feki, M. Mlik, F. Karray, A. Trigui, et al., [Blepharitis due to Demodex: myth or reality?], J Fr d’ophtalmologie 22 (1999) 525–537 (Accessed
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