Since the publication of the Age-Related Eye Disease Study (AREDS2) in 2013, the macular pigment carotenoids lutein and zeaxanthin have become well known to both the eye care community and the public.
It is a fascinating aspect of evolution that primates have repurposed photoprotective pigments and binding proteins from plants and insects to protect and enhance visual acuity. Moreover, the utilization of these plant-derived nutrients has been widely embraced for preventing vision loss from age-related macular degeneration (AMD).
More recently, there has been a growing awareness that these nutrients can also play a role in improving visual performance in adults. On the other hand, the potential benefits of lutein and zeaxanthin supplementation at very young ages have been underappreciated. Δ
At least 700 carotenoids are found in nature. About 50 are included in a typical human diet, 15–16 of which make their way to the circulatory system, but remarkably only 3 are found in the eye, where they are highly concentrated at the macula.
These yellow macular pigments—lutein, zeaxanthin, and meso-zeaxanthin—have powerful antioxidant properties and play essential roles in filtering high-energy, short-wavelength blue light and in minimizing the oxidative stress that is known to be a significant factor in age-related eye disease.
Lutein (L) and zeaxanthin (Z) are plant-derived pigments frequently consumed in a normal human diet that is naturally concentrated in the macula lutea (yellow spot) of the human eye where they are major components of the macular pigment (MP). Δ
They are lipophilic members of the xanthophyll carotenoid class that share a common C40H56O2 molecular formula. They have a rigid 22-carbon isoprenoid backbone with nine conjugated C=C double bonds. Ionone rings connect to each end of the backbone, two beta rings in the case of zeaxanthin, or one epsilon and one beta ring in the case of lutein
Age-related Macular Degeneration (AMD) is the first ocular disease to be conclusively linked to the MP carotenoids. This common cause of irreversible blindness in the elderly is due to some modifiable and non-modifiable risk factors including aging, heredity, smoking, excessive light exposure, and nutrition.
In the early and intermediate stages, there are deposits of oxidized lipids and proteins underneath the RPE known as drusen, thickening of Bruch’s membrane under the RPE, and increased levels of RPE lipofuscin, but visual function may still be near normal. Δ
In the advanced exudative or “wet” form of AMD, abnormal new vessels can infiltrate Bruch’s membrane or proliferate beneath the RPE, within the subretinal space, and even enter the retina itself.
This neovascular tissue can leak fluid and blood and cause irreversible macular scarring and blindness if left untreated. Intravitreal injections of anti-vascular endothelial growth factor (antiVEGF) compounds can combat wet AMD, but they may require long-term monthly in-office administrations of medications that are often very expensive and not always effective.
In the advanced dry stage of AMD, large patches of RPE and retina can die away in the macula, leaving sharply demarcated patches known as geographic atrophy that will cause central visual loss if the fovea is affected. Δ
Currently, there is no effective treatment to reverse or slow down dry AMD, but several complement inhibitors and other medications are in clinical trials.
John M. Nolan, PhD, has spent 20 years researching the macular pigments–measuring them and monitoring their effects on health. He says that “the general population is highly deficient in these; even the healthiest person you know is deficient. Nobody is eating enough.” A deficiency in macular pigments has a real and tangible impact on day-to-day quality of life in terms of vision and cognitive function. Δ
Everybody who works in eye care is aware that visual acuity does not describe the whole of visual performance, which is multifaceted and also incorporates aspects of processing speed, contrast sensitivity, glare, and visual adaptation.
Nolan’s European CREST trials, supported by a European Research Council Starting Grant, demonstrated that each of these individual visual functions is significantly improved by enriching the macular pigments through an oral supplement, not only in patients with early age-related macular degeneration but also in healthy study participants.
Blue light is a problem for visual performance and increasing its filtration—by increasing macular pigment—reduces visual discomfort and glare disability and improves photostress recovery. Another important aspect of vision is the speed of visual processing, which is strongly modifiable by increasing macular pigment. Δ
For every 0.1 increase in macular pigment optical density, roughly 1 millisecond of reaction time can be gained. Increased contrast sensitivity can hugely improve a patient’s quality of life and how they feel about their vision.
A patient with a medium or high level of macular pigments can develop macular degeneration, but nutrition can counterbalance genetic factors and optimize their disease trajectory.
It is important to measure the concentration of macular pigment in the eye itself because retinal levels correlate only weakly with levels in the blood; availability of the fat-soluble carotenoids at their target tissue depends on a patient’s body mass index amongst other factors.
Until fairly recently, it had been possible to quantify retinal concentrations using psychophysical methods only, which are known to be highly subjective and variable and also have the disadvantage of measuring at only 1 point in the eye.
Nolan has worked with Heidelberg Engineering to develop an experimental software add-on to the Spectralis system, which uses a dual-wavelength autofluorescence system to measure the “optical volume” of the macular pigments.
They have developed and validated macular pigment optical volume (MPOV) as an arbitrary unit that provides a measure of the concentration of the pigments within every pixel of the image, across the entire macula, thus allowing the distribution of the pigments to be mapped.
It is now possible to examine a patient and compare their MPOV with that of the general population average in terms of low or high levels of pigment.
Nolan’s current research interest is dementia and cognitive function. It has become clear that the levels of macular pigment measured in the eye correlate with their levels in the brain; it has been demonstrated further that these levels correlate directly with cognitive function.
The population of individuals with Alzheimer’s disease is the most deficient Nolan has encountered and he is currently conducting an interventional study in these patients.
This would not have been possible previously, as people with this dementia are not able to cooperate with psychophysical testing. The Spectralis system makes it possible to quickly and simply measure their macular pigment.
A cross-sectional observation study with 4000 participants in the Republic of Ireland demonstrated that individuals who had high levels of pigment outperformed everybody else in all measures of cognitive abilities.
Interventional trials found that memory and cognition in healthy patients improved on supplementation with the 3 macular pigments.
It is possible in principle to improve one’s levels of macular pigment by eating significant portions of plants such as spinach, kale and corn. Good nutrition is a baseline and the first step Nolan takes with his trial patients is to optimize their nutritional profile via diet.
A cost–benefit analysis that Nolan published in the Irish Medical Times showed clearly that across a 5-year period, in the population of the Republic of Ireland, using these supplements as standard could save over 250 million Euros from the health budget.