Meibomian gland disease (MGD) is a common disorder with a prevalence of 30% in patients younger than 30 years and 71.7% in individuals older than 60 years.1,2 Meibomian gland disease is characterized by inflammatory changes at the lid margin and meibomian orifices, which can lead to alteration and/or reduction of meibum, increased tear evaporation, dry eye symptoms, decreased tear stability, and damage to the ocular surface epithelium.3
The conventional treatment for MGD consists of warm compresses and lid hygiene,4,5 topical artificial tears, topical or systemic antibiotics,6,7 topical steroids,8 lipid eye drops,9 dietary management,10 as well as systemic androgen administration.11 Recently, the LipiFlow Thermal Pulsation system (LipiFlow; TearScience Inc., Morrisville, NC),12 probing therapy,13,14 and intense pulsed light15,16 have been reported to be effective for MGD, but they are expensive and/or invasive, and may necessitate technical expertise.
Lid expression, however, is a relatively cost-effective and a noninvasive therapeutic option, compared with other treatment modalities. Although therapeutic lid expression has been reported to be a useful approach and is recommended for the treatment of MGD,3 there have been no prospective clinical studies in the literature comparing no expression to digital or plate expression in terms of their effects on tear functions and ocular surface status. The purpose of the current study was to evaluate the clinical effectiveness of expression treatment after 1 month when used as an adjunct to routine medical management of MGD.
The study protocol was approved by the Tokyo Dental College Internal Review Board (date: March 30, 2016, number: I 16-02), and was registered to UMIN (UMIN000025159). Written informed consents were received from all subjects. The study followed the tenets of the Declaration of Helsinki.
During May 2016 to December 2016, we included patients older than 20 years who had MGD and who signed the informed consent forms. Eighteen eyes of 18 MGD cases (5 males, 13 females; mean age: 65.9±14.3 years) were randomly divided into 3 groups in this prospective clinical trial, using random number table generated using Excel. A masked examiner was used at the 1 month follow-up visit. The study was conducted during a determined time frame not subject to an extension, which resulted in the difference in the number of participants.
Meibomian gland disease was diagnosed according to the 2010 Japanese MGD workshop criteria17: a patient had to have chronic ocular discomfort, at least one abnormality around the meibomian orifices including vascular engorgement, mucocutaneous junction displacement, and eyelid margin irregularity, and signs of obstruction of the meibomian glands including both slitlamp findings of obstruction (pouting, plugging, ridge), and decreased meibum expression by moderate digital pressure.
Patients younger than 20 years, subjects with a history of Sjogren syndrome, Stevens–Johnson syndrome, chemical, thermal, or radiation injury, history of laser-assisted in situ keratomileusis and other refractive surgeries or cataract surgery within 1 year, all subjects wearing contact lenses, and subjects with systemic diseases or on medications inducing dry eye or MGD were excluded. Patients who were already under dry eye/MGD treatments were excluded. Pregnant or lactating mothers were also excluded from this study.
We divided all the subjects into no expression group, digital expression group, and plate expression group. Subjects in the no expression group underwent routine treatment with no expression (five patients, five eyes) (1 male, 4 females; mean age: 60.2±19.8 years). The digital expression group underwent routine treatment with digital expression (five patients, five eyes) (0 male, 5 females; mean age: 65.8±9.00 years). The plate expression group underwent routine treatment with plate expression (eight patients, eight eyes) (4 males, 3 females; mean age: 69.9±3.19 years).
All patients received routine treatment18 of MGD for 1 month, which consisted of applications of disposable eyelid-warming masks (Jo-ki de Hot Eye Mask; Kao, Tokyo, Japan) for 10 min twice a day, lid hygiene twice a day with a baby shampoo, 1.5% levofloxacin eye drops four times per day, 0.1% fluorometholone eye drops three times per day, 0.1% hyaluronic acid sodium eye drops four times per day, and 100 mg oral minocycline twice a day.
Upper and lower eyelids were divided into nasal, central, and temporal zones. Patients in the no expression group received no digital lid expression. In the digital expression group, digital expression was performed with a single moderate digital pressure. In the plate expression group, plate expression was performed using a plate expressor (Rhein Medical, St. Petersburg, FL) In both groups, meibum was expressed for 5 s from each zone after a single drop of oxybuprocaine hydrochloride anesthesia without preheating, and expression was performed only once at the time of enrollment in the study.
Two microliters of 1% fluorescein dye was instilled into the lower tear film meniscus using a micropipette without touching the eyelids or the ocular surface. The patients were then asked to blink a few times to ensure adequate mixing of the dye to the tear film. The tear film break-up time (TBUT) was assessed after a complete blink three times using a chronometer, and the mean of three measurements was recorded. A TBUT value of less than 5 s was regarded as short TBUT, according to the new diagnostic criteria of dry eyes of the Asia Dry Eye Society.19 For fluorescein staining assessment, the corneas were divided into upper, central, and lower zones and the amount of staining was graded from 0 to 3 points in each zone. Nine points constituted to a maximal corneal staining score. Finally, meibum expressibility was assessed using Shimazaki grading20,21 as shown in Table 1. Dry eye–related quality of life score (DEQS) questionnaire was also performed to assess dry eye symptoms. These findings were assessed at the beginning of the study and 1 month after treatment. Adherence was assessed at the follow-up visits by asking the patients how they performed their treatments in detail.
STATA SE 14 software (StataCorp LLC) was used for statistical analysis. One-way analysis of variance (ANOVA) with a post hoc test (Tukey test) was used for statistical comparisons among the groups. Paired t test was conducted to compare the pretreatment versus posttreatment findings within groups. A P value less than 5% was considered statistically significant.
There were no statistically significant age differences, except a significant sex difference among the groups. A single right eye from the plate expression group developed acute bacterial conjunctivitis during the conduct of the study and was excluded, and seven eyes from the plate expression group were analyzed (4 males, 3 females; mean age: 70.1±5.03 years). No subject complained of pain experience during or after the expression treatment. A representative image of plate expression is shown in Figure 1. All patients said that they were adherent to their treatment method as recommended in this clinical trial.
Change of Tear Film Break-up Time With Treatment
There was a statistically significant difference of posttreatment TBUT among the groups as determined by one-way ANOVA (P=0.029), although there was no significant difference in the pretreatment TBUT values. A Tukey post hoc test revealed that TBUT was statistically significantly higher in the plate expression group compared with the digital expression group (P=0.045). A paired t test showed that in the plate expression group, TBUT significantly improved after treatment (P=0.0023) (Table 2).
Changes of Cornea Fluorescein Staining Score With Treatment
The fluorescein staining score did not show a statistically significant difference among three groups in one-way ANOVA. The mean fluorescein staining score showed a significant improvement in the plate expression group (P=0.015) (Table 3).
Changes of Meibum Expressibility With Treatment
One of five eyes (20%) in the no expression and the digital expression group and two of seven eyes (29%) in the plate expression group showed the improvement of meibum expressibility score (Table 4).
Dry Eye–Related Quality of Life Score Questionnaire Results
There was a significant difference in baseline DEQS scores among the three groups. Although not statistically significant, many showed the improvement of DEQS after the treatment in all the groups (Table 5).
Among the clinically distinct forms of chronic blepharitis, meibomian keratoconjunctivitis has been shown to have a frequent association with plugging, inspissation, hyposecretion of meibomian lipids, and an unstable tear film.
Meibomian gland therapeutic expression has been reported to decrease tear evaporation in patients with MGD.22 Korb and Blackie23 reported that digital therapeutic expression is useful in MGD treatment and pain was the limiting factor for the conduct of this treatment. Although mechanical lid expression has been reported as a therapeutic modality in the treatment of MGD, there have been no prospective randomized clinical studies comparing mechanical lid expression to digital or no expression up until today. All groups showed improvement of tear stability, meibum expressibility, and corneal staining scores with treatment due to conduct of the same routine treatment. However, the plate expression group showed a statistically significant improvement of TBUT after the treatment among all groups. The comparably better effects on the tear film and ocular surface in this group, we believe, are due to better expression and removal of the inflamed meibum from the eyelids by mechanical expression. The preliminary findings from the current clinical study suggest that plate expression is an efficient therapeutic modality in improving tear stability when compared with no expression or digital expression. Our findings justify the conduct of similar trials on a larger number of subjects, which will definitely provide invaluable information. Clinical trials comparing conventional MGD treatment with lid expression to other expression techniques involving probing, serial intense pulsed therapy, or LipiFlow would also provide interesting insight into the treatment of this common disease.12,13,15,16 Whether the treatment effects by lid expression were sustainable and the duration of improvement after cessation of expression need to be clarified in future clinical trials.
In conclusion, plate expression is an efficient and an easy therapeutic modality that provides improvement of tear stability, meibum expression, and corneal epithelial damage scores after 1 month of treatment in MGD.
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