Condition category
Nutritional, Metabolic, Endocrine
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Thyroid eye disease (TED) is a chronic disfiguring and debilitating disease of the eyes which can lead to sight loss in severe cases. Patients with TED often have characteristic eyeball protrusion (proptosis) due to increased fat accumulation behind the eye. The discomfort and changes in appearance of the eyes is a source of severe psychological distress and reduced quality of life in many patients. Current treatments for TED are unsatisfactory and established nonsurgical therapies which specifically reduce proptosis are lacking. Reduced eyelid protrusion has recently been reported as a side effect of the use of prostaglandin analogue eye drops such as Bimatoprost (PGF2alpha) in the routine treatment of glaucoma and we have data showing inhibition of fat cells by Bimatoprost. Hence PGF2alpha eye drops potentially represent a simple, non-invasive low-toxicity alternative to surgery in TED. However, no clinical trials of Bimatoprost have been conducted in TED to date. The aim of this study is to determine whether Bimatoprost eye drops are effective in reducing proptosis and thus improving quality of life in patients with TED.

Who can participate?
Men and women aged 18 years and older from the TED clinic at the University Hospital Wales (Cardiff & Vale University Health Board). Only participants with stable, late, inactive thyroid eye disease will be enrolled. The clinic is a regional referral centre for the treatment and study of TED and is run by a multidisciplinary team of ophthalmologists, endocrinologists, and orthoptists with expertise in TED.

What does the study involve?
Following informed consent, you will be randomly allocated to use Bimatoprost or placebo (dummy) eye drops daily for three months, after which you will not use eye drops for two months, before switching to the opposite treatment in the final three months of the study. Patients will be followed up at one further visit 2 months later. You will be enrolled in the study for 10 months in total. There are six visits: before the start of the study, random allocation and four follow-up visits. You will be asked to complete quality of life questionnaires and a health economic questionnaire at each of the follow-up visits. Eye tests will be carried out before the start of the study and at follow-up visits.

What are the possible benefits and risks of participating?
If the treatment you are receiving is found to be better than the current standard treatment then you will benefit from participating in this study. Otherwise, taking part may not be of direct benefit to you. It should, however, help us to provide better care for patients with Thyroid Eye Disease in the future. Note that all participants will receive the active treatment at one stage of the study. The most common side effects after using Bimatoprost eye drops are an itching sensation in the eyes and/or eye redness. This was reported in about 4% of patients. Bimatoprost may cause other less common side effects which typically occur on the skin close to where it is applied, or in the eyes. These include skin darkening, longer or thicker eyelashes, dryness of the eyes and redness of the eyelids. Any eyelid skin darkening or eye lash thickening/elongation are expected to reverse after several weeks to months after stopping the eye drops. Bimatoprost use may also cause increased brown pigmentation (reported in about 1% of patients) of the coloured part of the eye known as iris which may be permanent. Bimatoprost eye drops have been in routine long-term clinical use in glaucoma for 12 years, and will be used in this study at the same dose as in glaucoma therapy. Drug formulations containing Bimatoprost have been in regular use for glaucoma for some time, and Bimatoprost preparations are available over the counter for cosmetic application, thus their safety is well established.

Where is the study run from?
University Hospital of Wales, Cardiff & Vale University Health Board, UK.

When is the study starting and how long is it expected to run for?
It is expected that recruitment will start in May 2014. You will be enrolled on the study for 10 months; however, it is expected that the study will run until February 2016 to complete data analysis.

Who is funding the study?
Research for Patient and Public Benefit Wales, part of National Institute for Social Care & Health Research (NISCHR), UK.

Who is the main contact?
Professor Colin Dayan

Trial website

Contact information



Primary contact

Prof Colin Dayan


Contact details

Institute of Molecular & Experimental Medicine
Cardiff University School of Medicine
University Hospital of Wales
C2 Link Corridor
Heath Park
CF14 4XW
United Kingdom
+44 (0)29 20 742182

Additional identifiers

EudraCT number

2014-000540-15 number

Protocol/serial number


Study information

Scientific title

Prostaglandin F2-alpha eye drops (BIMAtoprost) in thyroid eye disease: a randomised controlled double blind crossover trial



Study hypothesis

We hypothesise that topical treatment with Bimatoprost may reduce orbital tissue volume in noninflamed orbits and thereby improve quality of life in patients with thyroid eye disease (TED).

Ethics approval

Wales REC 3, initial approval obtained on 21/03/2014, REC reference: 14/WA/0081, substantial amendment 1 on 17/06/2014

Study design

Randomised placebo-controlled double-blind crossover design

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Graves' eye disease


Bimatoprost or placebo eye drops (daily application) for three months followed by a two-month drug washout period before switching to the opposite treatment in the final three months of study.

1 drop daily for 3 months (placebo or Bimatoprost)
Stop treatment for following 2 months
1 drop daily for following 3 months (cross over to either placebo or Bimatoprost)
Patients will be followed up at one further visit 2 months later

Intervention type



Not Applicable

Drug names


Primary outcome measure

Change in proptosis measurement; reduction of 2 mm or more would be regarded as clinically relevant. Measured at all visits (baseline, 2, 3, 4, 5). Measured by exophthalmometry readings by Hertel exophthalmometer.

Secondary outcome measures

1. Change in quality of life scores: measured at visits 1, 2, 3, 4, 5. Measured by EUGOGO GO-Quality of Life and EQ-5D-5L Health Questionnaire
2. Side effects: measured at visits 2, 3, 4, 5. Standardised questionnaire in the form of a patient diary log. Patients will be requested to record any side effects in their diary
3. Change in intraocular pressure: measured at visits baseline, 2, 3, 4, 5. Measured by Goldmann Applanation Tonometer
4. Health economic cost: measured at visits 1, 2, 3, 4, 5. Measured by Client Service Receipt Inventory (CSRI)

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Stable TED with no reported change in proptosis for at least 6 months
2. Clinical activity score <3
3. Proptosis (subjective unilateral proptosis confirmed by asymmetry in exophthalmometry of >2 mm OR greater than 20 mm on exophthalmometry measurement in one eye)
4. Euthyroid (FT3 and FT4 in the reference range)
5. If female, must be using a reliable form of contraception during the trial, e.g. oral contraceptive and condom, intrauterine device (IUD) and condom, diaphragm with spermicide and condom

Participant type


Age group




Target number of participants


Total final enrolment


Participant exclusion criteria

1. Age <18 years
2. Dysthyroid optic neuropathy unless previously treated
3. Pregnancy or lactation
4. Previous corneal herpes simplex infection
5. On therapy for glaucoma or intraocular hypertension
6. Less than 6 months from prior steroid use
7. Aphakia, pseudophakia with torn posterior lens capsule or anterior chamber lenses
8. Patient with risk factors for cystoid macular oedema, iritis or uveitis
9. Severe asthma (risk of severe allergic reaction to medication).
10. Previous allergy to Bimatoprost or preservative

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Institute of Molecular & Experimental Medicine
CF14 4XW
United Kingdom

Sponsor information


Cardiff University (UK)

Sponsor details

Innovation & Enterprise Services (RIES)
MacKenzie House
30-36 Newport Road
CF24 0DE
United Kingdom

Sponsor type




Funder type


Funder name

National Institute for Social Care & Health Research (Welsh Assembly Government) (UK) RFPPB20121015

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

It is intended that the results of the study will be reported and disseminated at local and international conferences and in peer-reviewed scientific journals.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date


Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

2019 results in: (added 13/06/2019)

Publication citations

Additional files

Editorial Notes

13/06/2019: Publication reference and total final enrolment added. 02/05/2018: The following changes were made: 1. Overall trial start date was changed from 01/05/2014 to 05/12/2012 2. Recruitment start date was changed from 01/05/2014 to 20/11/2014 3. Recruitment end date was changed from to 29/02/2016 12/02/2015 4. Overall trial end date was changed from 29/02/2016 to 15/04/2016 5. ORCID, publication and dissemination plan and participant level data were added. 27/03/2018: No publications found, verifying study status with principal investigator.