Contact information
Type
Scientific
Primary contact
Dr John Nolan
ORCID ID
Contact details
Macular Pigment Research Group
Waterford Institute of Technology
Cork Road
Waterford
-
Ireland
+353 (0)51 845 505
jnolan@wit.ie
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
IP/2007/0778
Study information
Scientific title
Macular pigment and its contribution to visual performance and comfort
Acronym
COMPASS
Study hypothesis
The macula is a specialised part of the retina, as it mediates central vision, provides sharpest visual acuity and facilities best colour discrimination. Lutein (L) and zeaxanthin (Z) are uniquely concentrated in the inner and central layers of the primate macula, where they are known as macular pigment (MP).
Age-related macular degeneration (AMD) is a disease of the macula and results in the loss of central and colour vision. AMD is the most common cause of blindness in the elderly population in the Western World. While the pathogenesis of AMD remains unclear, there is a growing consensus that cumulative short-wavelength visible light damage and/or oxidative stress play a role. MP is a short-wavelength (blue) light filter and a powerful antioxidant, and is therefore believed to protect against AMD. This "protective" hypothesis of MP has been studied in detail, and has been reported extensively in the literature. However, from a Darwinian perspective, it is unlikely that MP has evolved specifically to protect against AMD, as our increased lifespan is a recent phenomenon.
Beyond the "protective" hypothesis, a number of other theories have been put forward regarding MP function. Given that Darwinian natural selection is driven by phenotypic expression of genetic background, which confers an advantage before and until the period of procreation, it follows that the biological selectivity of MP's accumulation in the retina primarily represents an advantage in young and middle age. Since AMD is an age-related condition, seen only in persons greater than 55 years, it is doubtful that this degree of biological selectivity evolved to protect against these conditions. Indeed, from an evolutionary perspective, it is likely that the selective accumulation of L and Z at the macula confers an advantage in young and middle age and, therefore, that any such advantage of MP rests on its optical (rather than antioxidant) properties. In other words, it is likely that the primary role of MP rests on its contribution to visual performance.
These "optical" hypotheses of MP have been previously discussed and may be related to at least one of the following properties:
1. MP may enhance visual acuity by reducing chromatic aberration
2. MP may reduce visual discomfort by attenuation of glare and dazzle
3. MP may facilitate enhancement of detail by the absorption of "blue haze"
4. MP may enhance visual contrast
Unlike the "protective" hypothesis, few of the visual performance "optical" hypotheses have been empirically studied. However, some of these theories have been tested, and can be summarised as follows:
1. L/Z supplementation has been linked with improved visual function in patients with congenital retinal degenerations and with AMD
2. Visual discomfort resulting from a glare source has been shown to be much higher for short-wavelength light than for mid-or-long-wavelength light
3. Subjects with higher MP have been shown to be able to handle more short-wavelength light before an aversive response (quantified by electromicrogram [EMG] recordings of squinting) was elicited
4. Light absorption by MP has been shown to influence the amount of short-wavelength light necessary to elicit photophobia
However, all of the studies that have tested and commented upon the potential "optical" hypotheses of MP, as outlined above, should be interpreted with full appreciation of the small sample sizes in these studies.
In conclusion, while there are many interesting theories ("optical" hypotheses) suggesting that MP may play an important role in visual performance and visual comfort, empirical data are needed to test such hypotheses. In brief, therefore, a well-designed, well-powered, and properly executed technical study investigating MP's association with visual parameters and ocular comfort is truly merited. For example, does psychophysical visual performance relate to baseline MP levels? Does supplementation with L and Z enhance visual performance and/or ocular comfort? Should the answer to one or both of these questions be affirmative, the potential for market expansion will be unprecedented.
Ethics approval
Ethics approval received from:
1. The Waterford Institute of Technology Research Ethics Committee on the 12th June 2007
2. The Dublin Institute of Technology research ethics committee on the 17th August 2007 (ref: 13/07)
Study design
Randomised, placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Patient information sheet can be found at http://www.wit.ie/mprg
Condition
Enhancing vision performance and comfort
Intervention
This double blind placebo controlled study has two study arms:
1. The placebo formulation contains: lactose, cellulose, microcrystalline, magnesium stearate (core) and filmbuilding material with colorants and excipients (coating material)
2. The treatment formulation contains: two dietary compounds called lutein and zeaxanthin, carotenoids from Tagetes erecta, ascorbic acid, vitamin E acetate, selenium yeast, zinc oxide, cellulose, microcrystalline, silicon dioxide, magnesium stearate (core [actives and excipients]) and filmbuilding material with colorants and excipients (coating material)
All subjects (placebo = 60 subjects and treatment = 60 subjects) will be asked to take two tables per day for 12 months. Study visits will be at baseline, three months, six months and a 12 month exit visit. At each study visit, the following will take place: generic lifestyle questionnaire; vision questionnaire; macular pigment measurement; variety of vision performance tests (e.g. contrast sensitivity and glare recovery).
Contact for public queries:
Ms Eithne Connolly
MPRG project manager
Tel: 051 845505
Ms Connolly will answer any questions concerning the study, the procedures, and any outcomes that may appear to be related to the research.
Intervention type
Supplement
Phase
Not Specified
Drug names
Lutein-based nutritional supplement
Primary outcome measures
1. To determine whether a person's macular pigment optical density relates to visual performance and/or ocular comfort, measured using heterochromatic flicker photometry
2. To determine whether augmentation (through supplementation) of a person's macular pigment optical density results in enhanced visual performance and/or improved ocular comfort, measured via questionnaire and by a variety of objective vision assessment techniques
The primary and secondary outcome measures will be assessed at each study visit.
Secondary outcome measures
1. To determine whether changes in serum concentrations of lutein and zeaxanthin are associated with changes in macular pigment levels in normal subjects
2. To determine whether objective assessments of visual performance are associated with subjective, questionnaire based, assessments of visual performance
The primary and secondary outcome measures will be assessed at each study visit.
Overall trial start date
04/08/2008
Overall trial end date
31/03/2009
Reason abandoned
Eligibility
Participant inclusion criteria
1. Any race
2. Male or female
3. Aged 18 to 40 years
4. No presence of ocular pathology
5. Visual acuity of at least 6/18 in the study eye
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
120
Participant exclusion criteria
1. Outside age range 18 to 40
2. Pregnancy
3. Presence of ocular pathology
4. Cataract
Recruitment start date
04/08/2008
Recruitment end date
31/03/2009
Locations
Countries of recruitment
Ireland
Trial participating centre
Macular Pigment Research Group
Waterford
-
Ireland
Sponsor information
Organisation
Enterprise Ireland (Ireland)
Sponsor details
Glasnevin
Dublin
-
Ireland
+353 (0)1 808 2000
James.Ryder@enterprise-ireland.com
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Innovation partnership - Enterprise Ireland and Bausch & Lomb (Ireland) (ref: IP/2007/0778)
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