Dry eye disease (DED) is an emerging, under-recognized and under-treated epidemic of the
21st century. It is one of the commonest reasons seeking eye consultation worldwide.
Depending on the diagnostic criteria, geographic location and population concerned,
prevalence of DED ranges from 30 to over 50% in the Asia Pacific regions compared to
around 5-10% in the United States. Up to 90% of DED is closely associated with meibomian
gland dysfunction (MGD), a chronic and progressive condition characterized by terminal
duct obstruction, qualitative and/or quantitative changes in the glandular secretions
(meibum) which causes tear instability by increasing tear evaporation and subsequently
increased tear osmolarity, ocular surface inflammation, epithelial damage and ocular
surface disease. Studies suggest that MGD affects between 5-20 % of Caucasians and over
60% of Asians populations.
Conventional treatments for MGD including self-administered eyelid hygiene, eyelid warm
compress therapy (EW), artificial tears, including lipid-containing lubricants are
limited in their efficacies for moderate to advanced disease. Prescription medications
(topical steroids, topical and oral antibiotics, topical immunomodulatory agents e.g.
cyclosporine and oral omega-3 essential fatty acids) have demonstrated efficacies in
improving symptoms and signs of MGD; however side-effects including preservative-related
adverse events, development of antibiotic resistance, cost, accessibility, off-label use,
and the need for ongoing treatments often limit their long-term use.
Despite the described range of available options, management for MGDs is often considered
unsatisfactory and frustrating by clinicians and patients. Compliance to long-term,
home-based self-administered therapies is known to be suboptimal while
practitioner-administered treatment including meibomian gland expression (MGX) provides
transient relief.
Intense pulsed light (IPL) therapy is widely used in cosmetic dermatology as well as
therapeutically for a wide range of skin conditions with favourable efficacy and
tolerability. Concurrent MGD improvements were observed serendipitously in patients
undergoing IPL for rosacea. With growing interest in combining IPL+MGX as
practitioner-administered physical therapy for MGD, recent review and meta-analysis
showed its effectiveness and safety while calling to investigate its effect beyond 6
months after the last IPL treatment.
Vectored thermal pulsation (VTP) is approved by FDA as another practitioner-administered
physical therapy for MGD. The device covers both the cutaneous and mucosal surfaces of
the eyelids; the rear portion of the device provides heat to the MG, and the front
portion gives mechanical stimulation to the eyelid skin. It evacuates the MG of the upper
and lower eyelids simultaneously with minimal discomfort while protecting the cornea,
rendering the experience for patients generally favorable. Recent meta-analysis showed
that a single 12-minute VTP was more efficacious than EW in treating MGD.
Knowledge gaps:
Level I evidence comparing efficacies between two promising practitioner-administered
therapies VTP and multi-session IPL+MGX with standard self-administered twice-daily EW
for MGD is currently lacking. The onset and offset of therapeutic effects, time course of
multi-session IPL+MGX, single-session VTP or twice-daily EW on MGD up to 15-month
post-treatment initiation or 12-month post last session of IPL have not been studied
either in an RCT setting. These important gaps will be addressed in this application.
Primary Objective:
To compare the efficacy and safety of 1-session vectored thermal pulsation (VTP) or
4-session intense pulsed light and meibomian gland expression (IPL+MGX) with twice-daily
eyelid warm compress (EW) therapy for meibomian gland dysfunction (MGD).
Secondary Objectives:
To compare the course of MGD among groups over 15 months (12-month after final
IPL+MGX);
To identify factors predicting responses and compliance to therapies.
Hypotheses:
Both 1-session VTP and 4-session IPL+MGX are more efficacious than twice-daily EW in
improving MGD;
MGD improves earlier after VTP;
MGD improvement lasts longer after 4-session IPL+MGX.
Study design:
This is a prospective, randomized, assessor-masked, 3-arm (1:1:1), active-controlled
trial of 360 subjects with meibomian gland dysfunction contributing one study eye. For
subjects with both eyes eligible, the eye with the fewest quality of expressed meibum,
thinnest lipid layer, or the lowest TFBUT values (in this order) will be selected as the
study eye.
A total of 360 patients with symptomatic MGD will be recruited from the participating
hospitals coordinated by the Chinese University of Hong Kong (CUHK) Research Clinic, the
CUHK Eye Centre (CUHKEC), Department of Ophthalmology and Visual Science, Faculty of
Medicine, The CUHK.
Randomization will be carried out by a computer-generated minimization program.
Minimization is a dynamic process to reduce the imbalance between trial arms with respect
to a range of predefined prognostic variables, and a randomization schedule is therefore
not drawn up in advance. A form describing the baseline characteristics of each subject
according to these minimization criteria: gender, age, and quality of expressed meibum
from the study eye. Treatment allocation will be sent to the unmasked trial coordinator
for arrangement at baseline (month 0).
Enrolled patients will be randomized into one of the following groups, 1 month after
recruitment during the 15-month study period receiving bilateral treatment of:
Group A: 1-session VTP at month 0; Group B: 4-session IPL+MGX at month 0,1,2,3; Group C:
twice daily EW for 15 months.
All patients will be given one single topical lubricant (Hypromellose, 3mg/ml) to be used
as frequently as needed from recruitment to study exit (total 16 months).
IPL or VTP is given by unmasked treating investigators not involved in data collection.
Follow-up investigators collecting the data are masked to participants' treatment
assignment. This information can be disclosed upon request after the completion of the
study. Unmasked trial coordinators will ensure masking by reminding and accompanying each
patient before and during visit. Treatment-related complications will be evaluated by all
participants in a standard datasheet regardless of group assignment. Follow-up
investigators will be asked if they know each participant's group assignment at each
visit and why.
Tear film breakup time will be assessed as the primary outcome (month 6 and 15). Serial
measurements of MG, tear-film, DED-related parameters, intraocular pressure, compliance
to EW, factors associated with outcomes, and treatment-related complications will be
conducted by masked investigators at baseline and eight follow-up evaluations (month 0,
1, 2, 3, 4, 6, 9, 12, 15).