Study Design and Participants
This is a 3-month randomized, controlled trial comparing two eyelid-warming devices, EyeGiene® and Blephasteam®, and warm towel compress in MGD participants.
From February 2012 to October 2013, all patients at the Singapore National Eye Centre dry eye clinic who met the eligibility criteria were briefed about this study and invited for screening. The MGD in this study is not classified into severity levels but as long as the morphological eligibility criterion below and specified symptoms are present, they can be included. Eligible participants were then enrolled with written informed consent by the clinical trial coordinator.
Compliance with Ethics Guidelines
The study has been approved by the SingHealth Centralized Institutional Review Board and adhered to the tenets of the Declaration of Helsinki of 1975, as revised in 2000 and 2008.
These patients were included for the study:
At least one of eight dry eye symptoms (Supplementary Fig. 1—questionnaire modified after Schein et al. ) was experienced “often” or “all the time.”
At least one MG opening with pouting and a visible plug above the eyelid margin that cannot be removed by gentle wiping with a cotton tip.
No ocular pathology requiring treatment other than eye lubricant and conventional eyelid hygiene within the last month and during the study.
Participants with data at baseline and 1 month after treatment.
These patients were excluded from the study:
Known diagnosis of thyroid dysfunction and rheumatoid arthritis.
Ocular surgery within the previous 6 months and laser-assisted in situ keratomileusis (LASIK) within the previous year.
Central nervous system and hormonal drugs required within the last month and during the study.
Active ocular infection or presence of pterygium.
Necessity to wear contact lens during the study.
Living in the same household as another participant of the study.
Randomization and Blinding
The nursing manager and two witnesses drew lots to determine the random allocation sequence of participants to the three treatment methods in a 1:1:1 ratio. The assessor of the participants’ clinical signs was blinded to the treatment method of each participant.
All participants were required to self-administer the eyelid-warming therapies twice daily, for 10 min each time, then briefly massage their eyes and clean their eyelids with Blephagel® (Spectrum Thea Pharmaceuticals LTD, Macclesfield, UK) and cotton pads.
Participants were given a towel to warm in warm water before placing it over their eyes. They were instructed to re-warm the towel when they feel it get cooler.
The manufacturer claims that when the chemicals in the disposable sachets are mixed together and placed in the pockets of the eye mask, they deliver 40 °C heat to the eyelids for 8–10 min. The clinical trial coordinator would demonstrate how to activate the warming unit and use the eye mask as well as watch the participant activating one warming unit.
The Blephasteam® goggles are electrically powered and have to be preheated for 15 min. New Blephasteam® rings were moistened and fitted in the goggles before each 10-min session. Printed instructions from Blephasteam® were provided to each Blephasteam® participant.
Compliance Measures and Concurrent Medications
The participants were given a diary to record details of each treatment session (time and duration), eyelid cleaning with Blephagel® and use of eye lubricant. Participants were allowed to use eye lubricants but not antibiotics, steroid and anti-inflammatory eye drops such as cyclosporine as stipulated in the inclusion criteria.
Efficacy Outcome Measures
The primary efficacy outcome was the proportion of participants with improvement in severity and frequency of eye discomfort after 1 month of treatment. The secondary efficacy outcomes were the proportions of participants with improvement in symptom severity and frequency between 1 and 3 months of treatment. The symptom severity and frequency were performed on a visual analog scale as previously described . The details of all the study procedures are provided in the supplementary file.
Adverse events (AEs) and serious adverse events (SAEs) were monitored but the pre-specified safety outcome was changed in VA after 3 months of treatment. This is because a previous study found VA to be affected by lid warming .
Exploratory Efficacy Outcomes
Our exploratory outcomes were the changes in TBUT, number of plugged MG openings, corneal fluorescein staining and Schirmer’s test after 1 and 3 months of treatment.
Sample Size Calculation
There was little literature on the magnitude of symptom change on this scale that would be clinically significant. Based on clinical assumption, and taking into account the cost of the eyelid-warming devices, the authors endeavored to detect a 40% difference in proportion of participants with the primary outcome of improved symptom severity/frequency between the EyeGiene®/Blephasteam® and the warm towel groups after 1 month of treatment. Conservatively, the proportion of warm towel participants (the current practice) with improved severity/frequency was assumed to be 40%. Hence, 22 participants in each study arm were required for 80% power and a two-sided significance level of 5%. Therefore, the aim was to recruit 25 participants per arm to allow for three losses to follow-up or withdrawals per arm.
Data were checked for normality to determine the appropriate parametric or non-parametric test. To test for differences among groups, relevant Chi square test, one-way analysis of variance (ANOVA) and Kruskal–Wallis equality-of-populations rank test were used. Where there was difference among groups, the authors performed the relevant Student’s t test or Wilcoxon rank sum test. Chi square test was used to evaluate the differences in the primary and secondary outcomes between groups. Logistic regression was used to adjust for baseline differences. The analysis was by intention to treat. Statistically significant difference was based on 0.05 level of significance. All analyses were performed with Stata software, version 12.1 (StataCorp. College Station, TX, USA).