Condition category
Eye Diseases
Date applied
11/09/2013
Date assigned
02/10/2013
Last edited
12/08/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The eye condition glaucoma is a leading cause of blindness worldwide. With the rapidly growing and ageing global population, there will be an increase in the number of individuals affected by glaucoma. The prevalence of glaucoma is estimated to increase from 60 million in 2010 to 80 million by 2020. Current treatment options are limited to halting disease progression and do not restore lost visual function. It is well recognised that vision impairment (reduced visual function) from glaucoma is a major contributing factor to falls and car accidents. Disability glare impairs vision when light scatters within the eye. This occurs when there is a bright light on a background of low light levels resulting in the loss of image contrast and difficulty seeing dull objects near the source of glare. Disability glare is commonly experienced by glaucoma patients and has been shown to be present even in those who are mildly affected by the disease .The use of tinted glasses is of no benefit in disability glare and may in fact cause further visual impairment. Macular pigment is believed to play an important role in visual performance including glare sensitivity.
Macular pigment (MP) is highly concentrated at the macula, the central area of the retina responsible for central vision. The macular pigment optical density (MPOD) in an individual's eye can be measured using a macular densitometer. MPOD decreases with increasing age. There is evidence that dietary MP supplementation can lead to normal MPOD in healthy individuals and those with age-related macular degeneration (AMD). It has been shown that when healthy individuals or those with AMD were supplemented with dietary MP, their visual performance improved.
Glaucoma patients commonly complain of disability glare and the cause of this is poorly understood. Individuals with AMD also suffer from disability glare and have reduced MPOD. This prompted us to explore the role of MP in glaucoma patients. We have recently demonstrated that individuals with glaucoma have reduced MPOD compared to healthy age-matched controls. In this study, we aim to investigate the effects of dietary MP supplementation on the MPOD and visual function of glaucoma patients.

Who can participate?
Individuals attending the Eye Clinic at the Mater Misericordiae University Hospital or Mater Private Hospital for the management of their glaucoma, age > 18 years old. The healthy controls are individuals with no history of glaucoma.

What does the study involve?
All glaucoma participants will undergo a series of non-invasive vision-related tests and fill out questionnaires at their first clinic visit. Participants will be randomly allocated to receive either a dietary MP supplement (MacuShield®) or placebo (dummy).The placebo will only contain sunflower oil but will look exactly like MacuShield®. Each glaucoma participant will take one capsule daily, preferably with a meal for a duration of 6 months. At the end of the 6 months, all glaucoma participants will return for repeat of their vision-related tests and questionnaires. We are also inviting healthy controls to come in for the same testing as the glaucoma participants so that we will have a direct comparison. However, the healthy controls will not undergo intervention and do not require further follow-up visits.

What are the possible benefits and risks of participating?
You may or may not receive any direct benefit from taking part in the research study. However, information obtained during the course of the study may improve our understanding of your condition. We hope that the treatment that you get may reduce your glare symptoms. However, this cannot be guaranteed. The information we get from this study may help us to improve the treatment of future glaucoma patients. MacuShield® is a natural product that is widely available over the counter. There are no long-term side effects to MacuShield® and it has been tested safe for human consumption in a large-scale clinical trial in Ireland. The only documented and uncommon short-term side effect of lutein supplementation in humans has been carotenodermia, which is a harmless and reversible skin hyperpigmentation (darkening of skin).

Where is the study run from?
The study will take place at the Institute of Ophthalmology, Dublin, Ireland. Study subjects will be recruited from the Mater Misericordiae University and Mater Private Hospitals.

When is the study starting and how long is it expected to run for?
The study is expected to start in October 2013 and run until December 2014.

Who is funding the study?
Howard Foundation and MacuVision Europe Ltd.

Who is the main contact?
Professor Colm O'Brien, cobrien@mater.ie
Dr James Loughman, james.loughman@dit.ie

Trial website

http://www.dit.ie/optometry/people/jamesloughman/research/

Contact information

Type

Scientific

Primary contact

Prof Colm O'Brien

ORCID ID

Contact details

Institute of Ophthalmology
No. 60
Eccles Street
Dublin
7
Ireland
+ 353 (0)1 885 8616
cobrien@mater.ie

Type

Scientific

Additional contact

Dr James Loughman

ORCID ID

Contact details

Dublin Institute of Technology
Kevin Street
Dublin
8
Ireland
-
james.loughman@dit.ie

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Macular Pigment and Glaucoma Trial: a placebo-controlled, double-masked study

Acronym

Study hypothesis

This is a research study looking at the effects of oral dietary macular pigment (MP) supplementation in an individual with glaucoma. MP is a naturally occurring pigment located at the back of the eye. MP plays an important role to maintain good visual function including glare sensitivity. We have found that patients with glaucoma have reduced MP levels in their eye, which is a new finding [Igras E, Loughman J, Ratzlaff M, O'Caoimh R, O'Brien C. Evidence of lower macular pigment optical density in chronic open angle glaucoma. Br J Ophthalmol. 2013;97(8):994-8]. Studies have shown that oral dietary MP supplement can increase MP profiles to a normal level and improve glare sensitivity in healthy individuals and those with age-related macular degeneration. Individuals with glaucoma commonly suffer from glare and the cause of this is poorly understood. Here, we would like to study whether dietary MP supplementation will reduce glare symptoms among individuals with glaucoma. We would also like to understand whether dietary MP supplementation has any impact on glaucoma and the individual's quality of life.

The specific objectives of this research are as follow:
1. Establish the macular pigment optical density (MPOD) response to dietary MP supplementation in glaucoma patients
2. Investigate the visual response to dietary MP supplementation in glaucoma patients
3. Identify the relationship between MP and visual function in glaucoma patients compared to normal subjects

Objective 1: Establish the MPOD response to dietary MP supplementation in glaucoma patients
To our knowledge, the association of MPOD and glaucoma has not previously been explored unlike that of age-related macular degeneration (AMD). Our research group has recently published findings from our pilot study that showed glaucoma patients have reduced MPOD, which is a new and exciting finding. Dietary MP supplementation has been shown to increase MPOD in healthy subjects and patients with AMD. There has been no published data on the relationship between dietary MP supplementation and MPOD response in glaucoma. Here, we would like to investigate MPOD response to dietary MP supplementation in glaucoma patients. We hypothesise that the MPOD of glaucoma patients will increase following dietary MP supplementation as such a desirable response has previously been shown in healthy subjects and patients with AMD. To our knowledge, this will be the first study to establish MPOD response to dietary MP supplementation in glaucoma patients.

Objective 2: Investigate the visual response to dietary MP supplementation in glaucoma patients
There is evidence that MP may play a role in visual performance and this is attributed to its preferential spectral absorption for short wavelength blue light. The capability of MP to attenuate longitudinal chromatic aberration and to reduce scattered short wavelength light in the background improves retinal image quality and target contrast respectively allowing better visual performance. It has previously been shown that dietary MP supplementation increases MPOD and improves visual performance in individuals with AMD. The relationship between MPOD and visual function among healthy volunteers has also been demonstrated by other clinical trials. We aim to study whether a positive increment in MPOD following dietary MP supplementation in glaucoma patients will translate to an improvement in visual function such as visual acuity, visual field, glare disability, contrast sensitivity and PRT.

Objective 3: Identify the relationship between MP and visual function in glaucoma patients compared to normal subjects
We also propose to investigate the baseline relationship between MPOD and glaucoma. The glaucoma structure-function relationship will be assessed using the heterochromatic flicker photometry, spectral domain optical coherence tomography (SD-OCT, RTVue-100) and standard automated perimetry Humphrey field analyzer (HFA) Swedish Interactive Threshold Algorithm (SITA) 24-2 and 10-2 tests. The heterochromatic flicker photometry instrument measures the MPOD while the SD-OCT (RTVue-100) will assess the retinal ganglion cell complex thickness (GCCT), macular peripapillary retinal nerve fiber layer thickness (mpRNFLT) and central foveal thickness (CFT). There is evidence that individuals with progressing glaucoma as determined by visual field loss have reduced macular thickness on optical coherence tomography (OCT). Even in the absence of visual field loss, glaucoma patients have significantly lower GCCT and circumpapillary RNFLT when compared to healthy individuals. In our study, the macular visual field will be recorded using Humphrey 10-2 test. Na et al recently showed that the GCCT has a greater structure-function association with the macular visual field than that of the mpRNFLT. Here, we plan to investigate the association of glaucoma-related structural parameters in particular GCCT with that of MPOD. There have been studies that compared MPOD to central foveal thickness as measured by OCT in healthy subjects. Liew et al and van der Veen et al found a significant and positive relationship between MPOD and central foveal thickness while studies carried out by Nolan et al and Kanis et al showed no relation. These conflicting findings may be explained by methodological differences. Here, we would like to understand the relationship between MPOD and visual function and the underlying retinal structures related to glaucoma. Results obtained from glaucoma patients can be compared to those obtained normal subjects (healthy controls).

Ethics approval

Research Ethics Committee board (Mater Misericordiae University Hospital & Mater Private Hospital), 31/05/2013, ref: 1/378/1535

Study design

Single-centred randomised placebo-controlled double-masked study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Patient information can be found at: http://www.dit.ie/optometry/people/jamesloughman/research/patientinformation/

Condition

Glaucoma and disability glare

Intervention

120 Glaucoma participants
Treatment arm - MacuShield® (N=60)
Placebo arm (N=60)
Duration of intervention: 6 months

At baseline, all glaucoma participants will undergo detailed vision assessments such as visual acuity, slit- lamp examination, standard automated perimetry tests, measurement of macular pigment optical density (MPOD), optical coherence tomography scans, glare and contrast sensitivities and photostress recovery time, and fill out vision-related and dietary questionnaires. After the baseline assessments, glaucoma participants will be randomised (1:1) to receive a dietary MP supplementation (MacuShield®) or placebo for 6 months. Each daily dose of MacuShield® contains 10mg Lutein, 10mg meso-Zeaxanthin and 2mg Zeaxanthin in a softgel capsule. The intervention consists of a daily oral consumption of one softgel capsule for a period of 6 months. The placebo will look identical to MacuShield® in its preparation size, colour, smell and taste. It will contain no active ingredients but sunflower oil only.

Sixty age-matched healthy controls will also be recruited for comparison but they will not undergo any intervention.

Intervention type

Supplement

Phase

Drug names

Primary outcome measures

1. Macular pigment optical density (MPOD) response to dietary macular pigment (MP) supplementation in glaucoma patients. MPOD will be measured using the Macular Densitometer.
2. Visual response to dietary MP supplementation. Visual function assessments include the measurements of best corrected visual acuity (Logmar ETDRS chart), macular visual field test (Humphrey 10-2), glare and contrast sensitivities (Optec 6500 device) and photo-stress recovery time (MDD-2 Macular Adaptometer).

Measured at baseline and repeated again at 6 months after intervention.

Secondary outcome measures

1. Relationship between MP and visual function in glaucoma patients and healthy controls
2. Effect of MP supplementation on vision-related quality of life

Scores from the GAL-9 and TyPE SPEC (vision-related quality of life) questionnaires will be compared before and after dietary MP supplementation.

Overall trial start date

01/10/2013

Overall trial end date

31/12/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Glaucoma patients or healthy controls aged 18 years and above
2. Either gender
3. Able to give informed consent, make the required study follow-up visits and adhere to study protocol.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

120 glaucoma participants and 60 age-matched healthy controls

Participant exclusion criteria

1. Underlying ocular disease such as age-related macular degeneration, diabetic retinopathy or moderate to significant cataract (using Lens Opacity Classification System III grading)
2. Best corrected visual acuity of worse than 6/12 in the test eye.
3. Previous ocular surgery other than for cataract extraction or glaucoma drainage procedure.
4. Any individual who has a blue-light filter intraocular lens.
5. Individuals who already are taking dietary MP supplementation.

Recruitment start date

01/10/2013

Recruitment end date

31/12/2014

Locations

Countries of recruitment

Ireland

Trial participating centre

Institute of Ophthalmology
Dublin
7
Ireland

Sponsor information

Organisation

The Howard Foundation (UK)

Sponsor details

c/o HFH Group
PO Box 1187
Cambridge
CB22 5WB
United Kingdom

Sponsor type

Charity

Website

http://www.howard-foundation.com/trustees.htm

Funders

Funder type

Charity

Funder name

The Howard Foundation (UK) (Reg UK Charity No. 285822)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

MacuVision Europe Ltd

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results of pilot study in http://www.ncbi.nlm.nih.gov/pubmed/23686328
2015 baseline results in: http://www.ncbi.nlm.nih.gov/pubmed/26249732

Publication citations

  1. Results

    Igras E, Loughman J, Ratzlaff M, O'Caoimh R, O'Brien C, Evidence of lower macular pigment optical density in chronic open angle glaucoma., Br J Ophthalmol, 2013, 97, 8, 994-998, doi: 10.1136/bjophthalmol-2013-303153.

  2. Results

    Siah WF, Loughman J, O'Brien C, Lower Macular Pigment Optical Density in Foveal-Involved Glaucoma, Ophthalmology, 2015 , doi: 10.1016/j.ophtha.2015.06.028.

Additional files

Editorial Notes