Collaborative Optical Macular Pigment ASsessment Study

ISRCTN	ISRCTN35481392
DOI	https://doi.org/10.1186/ISRCTN35481392
Protocol serial number	IP/2007/0778
Sponsor	Enterprise Ireland (Ireland)
Funder	Innovation partnership - Enterprise Ireland and Bausch & Lomb (Ireland) (ref: IP/2007/0778)

Submission date: 05/06/2008
Registration date: 24/07/2008
Last edited: 11/06/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Eye Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr John Nolan
Scientific

Macular Pigment Research Group
Waterford Institute of Technology
Cork Road
Waterford
-
Ireland

Phone	+353 (0)51 845 505
Email	jnolan@wit.ie

Study information

Primary study design	Interventional
Study design	Randomised, placebo-controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Macular pigment and its contribution to visual performance and comfort
Study acronym	COMPASS
Study objectives	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(s)	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)
Health condition(s) or problem(s) studied	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
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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.
Completion date	31/03/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	120
Total final enrolment	121
Key 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
Key exclusion criteria	1. Outside age range 18 to 40 2. Pregnancy 3. Presence of ocular pathology 4. Cataract
Date of first enrolment	04/08/2008
Date of final enrolment	31/03/2009

Locations

Countries of recruitment

Ireland

Study participating centre

Macular Pigment Research Group

Waterford
-
Ireland

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	02/03/2011	11/06/2019	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

11/06/2019: Publication reference and total final enrolment added.