Purpose
This study is aimed at comparing the effects of tea tree oil (TTO) shampoo with regular eyelid shampoo on the treatment of meibomian gland dysfunction (MGD) signs and symptoms.
Design
Double-masked randomized clinical trial
Methodology
Forty patients with MGD were treated by daily eyelid scrubbing with TTO shampoo in one eye and regular eyelid shampoo in the other one. Before treatment and then after 1 and 3 months, the effect on ocular surface symptoms, tear production and stability, and conjunctival and eyelid signs of the 2 eyes were compared.
Results
Plugging and capping of meibomian gland orifices, foamy tear, glands expressibility, 5-Item Dry Eye Questionnaire score (DEQ5), and tear breakup time were improved more significantly in TTO shampoo–treated eyes (capping P = .050, plugging and glands expressibility P = .001, others P < .001). In spite of improvement in both eyes, scores of meibum quality, conjunctival hyperemia, corneal and conjunctival staining, and Schirmer1 test value showed no statistically significant difference between the eyes ( P = .06, .187, .192, .19, respectively). Moreover, eyelid margin telangiectasia resolved only in TTO shampoo–treated eyes ( P < .001). Trichiasis and distichiasis changed in neither group ( P > .99). Furthermore, ocular surface irritation during scrubbing was more common with TTO shampoo ( P = .002).
Conclusion
TTO shampoo was found to be more efficient than regular eyelid shampoo in controlling MGD signs and symptoms although ocular surface irritation during its application was more frequent.
M eibomian gland dysfunction (MGD) is a chronic disorder of meibomian glands of ciliary margin of the eyelids, diagnosed by obstruction of the gland orifices and qualitative and quantitative changes in their secretions. It is a common ocular disorder with many potential risks in healthy populations. This disorder is one of the main causes of dry eye disease all around the world. Its prevalence varies across different populations. In the Caucasian population, it has been reported to range from 3.5% to 19.9% and in the Asian population up to 60%.
There are different methods for treating it, of which eyelid hygiene constitutes the basic component of treatment. Tea tree oil (TTO) is an oil extracted from the leaves of a plant named Melaleuca alternifolia , a species of tea tree. , According to the studies carried out, it has antibacterial, , antifungal, , antiviral, and anti-inflammatory properties. This oil is used in local form for treatment of blepharitis (particularly those accompanied by Demodex folliculorum mite) successfully with no special side effects. The role of demodex in MGD pathogenesis has not been identified yet. Because of its antibacterial and anti-inflammatory performance, TTO may be useful for recovering from signs and symptoms of MGD.
To date, few studies have evaluated the effect of TTO on ocular surface diseases, most of which have had investigations into its effects on anterior blepharitis accompanied by demodex. To our knowledge, few studies have been conducted specifically on the effects of this substance on the signs and symptoms of MGD. Because of the anti-inflammatory effects of TTO and the results of previous studies on its therapeutic effects on blepharitis, we aimed to compare the effects of TTO with those of regular eyelid shampoo on improving the signs and symptoms of MGD.
Materials and Methods
Subjects
This prospective parallel randomized clinical trial was done at Khatam-al-Anbia Eye Hospital, Mashhad, Iran, from April 2014 to December 2014. It was approved by the ethics committee of Mashhad University of Medical Sciences and was conducted with strict adherence to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all patients for participation, treatment, and publication of data before entering the study. It was registered in the Iranian Registry of Clinical Trials (registration reference: IRCT20201219049753N1).
Patients with MGD aged 18-70 years who had no history of the following were included in the study: systemic medications affecting tear production (antihistamines, antidepressants, etc), any topical medication such as steroids during the past 4 weeks, ocular surgery, other ocular or systemic diseases involving ocular surface (Sjogren syndrome, chemical damage, history of head radiation, Stevens-Johnson, diabetes mellitus, acne rosacea, etc), infectious keratoconjunctivitis, and contact lenses. The diagnosis of MGD was mainly based on the diagnostic criteria for obstructive MGD proposed by the Japanese MGD Working Group. MGD was considered to be present when all of the following 3 signs/findings were positive:
- 1.
Chronic ocular discomfort
- 2.
Anatomic abnormalities around the meibomian gland orifices (at least 1 of them): vascular engorgement, anterior or posterior displacement of the mucocutaneous junction, or irregularity of the eyelid margin
- 3.
Obstruction of the meibomian glands (both of them): obstructive findings of the gland orifices by slit-lamp biomicroscopy (pouting, plugging, or ridge) and decreased meibum expression by moderate digital pressure
The patients for whom the disease severity was significantly different between the 2 eyes were excluded from the study.
Treatments
Each patient was given 2 solutions, ophthalmic cleansing shampoo containing TTO (EYESOL, ingredients: purified water, Melaleuca alternifolia (tea tree) oil 1%, lauryl citrate, peg-5 nitrogene, nickle cacaomo descilate) and Johnson’s baby shampoo, both of which were packed by the Eyesol laboratory in entirely similar containers with no name.
They received either regular eyelid or TTO shampoo for each eye randomly based on the simple random sampling method. Two boxes, one containing TTO and the other containing regular eyelid shampoo, were labeled with A and B by the manufacturer. For each patient, A and B were determined by lot for the eyes. Both physician and patient were unaware of the contents of the containers. The method of application was explained to the patients. After washing hands, a cotton bud was to be moistened with the solution. Then, with the index finger of the other hand, they had to gently hold down the lower eyelid and look up. Eyelashes and eyelid margin were to be rubbed gently with the bud for 60-90 seconds. Afterward, they had to gently hold up the upper eyelid and look down and rub the upper eyelid margin. After each application, eyes and eyelids were to be rinsed thoroughly with clean water. Participants were asked to use only the solution allocated for each eye.
Other medications including topical steroid and lubricant were prescribed according to the severity of signs and symptoms in each patient. Apart from the washing solutions, other treatments were entirely the same in both eyes.
Before treatment and then, at intervals of 1 and 3 months, symptoms of disease in each eye were separately asked using the 5-Item Dry Eye Questionnaire (DEQ5), and the signs were evaluated by slit-lamp examination.
Clinical Measurements
We compared the effect of TTO shampoo with that of regular eyelid shampoo on treating MGD symptoms (itching, sensation of dry eye, foreign body sensation, photophobia, irritation), ocular signs (redness, conjunctiva and corneal staining, tear break-up time [TBUT], vascularity, plugging and capping of gland orifices, trichiasis, distichiasis, Schirmer1, and expressibility of glands) and the type and prevalence of possible side effects (eg, skin irritation, redness, and itching).
First, all patients filled in the DEQ5 questionnaire. Then, we looked for foamy tear, conjunctival hyperemia, telangiectasia of eyelid margins, trichiasis, distichiasis, and capping and plugging of meibomian gland orifices (elevations of the meibomian gland orifices and oil droplets on eyelid margin, respectively) ( Figure 1 ). Then, the Schirmer paper strip was placed at the junction of the middle and lateral thirds of the lower eyelid within the inferior cul-de-sac, without topical anesthetic, with the eye closed, and its wetting was determined after 5 minutes (Schirmer1 test). Next, a fluorescein strip was moistened with saline and applied to the inferior cul-de-sac. Afterward, the interval between the last blink and the appearance of the first dry spots on the cornea was recorded (TBUT). In addition, fluorescein staining of the cornea and temporal and nasal conjunctival zones were scored after matching the Oxford scoring system panels, with a grade score 0 to 5 per zone (total range, 0-15). Furthermore, meibomian gland expressibility was determined by simultaneous expression from approximately 8 glands (occupying the central one-third of the lower eyelid length, ie, 8/24 glands) by firm digital pressure. It was scored according to the number of the 8 glands from which a fluid secretion can be expressed, regardless of its qualitative appearance (0 = all glands expressible, 1 = 3-4 glands expressible, 2 = 1-2 glands expressible, 3 = no glands expressible). Finally, the quality of expressed lipid was evaluated in appearance and scored as follows: clear fluid (0), cloudy fluid (1), viscous fluid containing particulate matter (2), and densely opaque, inspissated, toothpaste-like material (3). Meibum quality score was defined by summation of scores of expressed glands. As it was mentioned earlier, all variables were defined and scored according to the recommendation of the international workshop on MGD signs.
Statistical Methods
Sample size was estimated based on the results of repeated measures analysis of variance and G*power software. So, by using the effect size of 0.2, the test power of 0.8 and the significance level of 0.05, the sample size was 80 (ie, 40 for each group). The effect size was estimated based on the pilot sample that was taken from the population. To compare and analyze data of the 2 eyes, SPSS software (IBM Corp, version 21, Armonk, New York, USA) was employed. The statistical tests of repeated measures analysis of variance and logistic regression model of repeated measurements were used for quantitative and qualitative variables, respectively. Considering 95% for CI (confidence interval) and 5% as the significance level of the tests, the models were fitted. Until the end of the statistical analysis, the researchers were unaware of the contents of the containers.
Results
Forty patients with MGD were enrolled in this study, including 23 (57.50%) men and 17 (42.50%) women, with an average age of 49.15 ± 21.15 years (28-70 years).
Tea Tree Oil Shampoo–Treated Eyes
The mean DEQ5 score was 7.00±2.59 before treatment. It decreased to 3.97±2.03 after 1 month of treatment and then to 1.13±1.47 after 3 months of treatment. This result was statistically significant ( P < .001). The mean glands expressibility score decreased from 2.65±1.63 to 1.13±1.20 and 0.22±0.58 after 1 and 3 months of treatment, respectively ( P < .001). The mean meibum quality score was 11.08±5.01 before treatment. It decreased to 7.60±4.56 and 4.20±3.83 after 1 and 3 months of treatment, respectively. This result was statistically significant ( P < .001), too. The mean conjunctival hyperemia score decreased from 0.40±0.87 to 0.03±0.16 ( P < .001) and the Oxford Staining Score also decreased from 1.95±3.13 to 0 ( P < .001) after 3 months of treatment. The mean TBUT increased from 7.18±1.55 to 8.95±1.60 ( P < .001), and the Schirmer1 score also increased from 7.05±2.24 to 9.58±2.11 ( P < .001) after 3 months. Extent of capping and plugging of meibomian gland orifices, foamy tear, and ciliary margin telangiectasia were improved after 3 months of treatment. These results were also statistically significant ( P < .001).
Regular Eyelid Shampoo–Treated Eyes
The mean DEQ5 score was 6.95±2.46 before treatment. It decreased to 5.43±2.28 after 1 month of treatment and then to 4.02±1.99 after 3 months of treatment. This result was statistically significant ( P < .001). The mean glands expressibility score decreased from 3.28±1.69 to 2.60±1.65 and 1.92±1.80 after 1 and 3 months of treatment, respectively ( P < .001). The mean meibum quality score was 11.72±5.97 before treatment. It decreased to 9.65±5.54 and 7.63±4.79 after 1 and 3 months of treatment, respectively. This result was statistically significant ( P < .001), too. The mean conjunctival hyperemia score decreased from 0.58±1.11 to 0.20±0.52 ( P < .001) and the Oxford Staining Score also decreased from 2.28±3.33 to 1.05±1.91 ( P < .001) after 3 months of treatment. The mean TBUT increased from 6.53±1.59 to 7.40±1.26 ( P < .001) and the Schirmer1 score also increased from 7.15±2.17 to 8.45±2.24 ( P < .001). Extent of capping and plugging of meibomian gland orifices and foamy tear were improved after 3 months of treatment. These results were also statistically significant ( P < .001). Ciliary margin telangiectasia did not improve after 3 months of treatment ( P > .99).
Trichiasis and distichiasis changed neither in the TTO nor in the regular eyelid shampoo–treated groups ( P > .99).
Group Comparison
Both groups showed decrease in scores of DEQ5 and glands expressibility, extent of capping and plugging of meibomian glands and foamy tear after 1 month of treatment, and further decrease was observed after 3 months. Improvements of these measurements in the TTO group were significantly more than those of the other group (capping P = .050, plugging and glands expressibility P = .001, others P < .001). Both groups showed TBUT score increase after 3 months of treatment, but higher increase was seen in TTO shampoo–treated group ( P < .001). No statistical difference was found in the mean scores of meibum quality ( P = .060), conjunctival hyperemia ( P = .187), Oxford Staining ( P = .192), and Schirmer1 ( P = .191) between the 2 groups ( Table 1 ).
