CET Dietary macular carotenoid supplements and drusen resolution

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Dietary macular carotenoid
supplements and drusen
resolution
48
Course Code C-17541 O
Shamina Asif, BSc (Hons), MCOptom, Dr John Nolan, BSc (Hons), PhD
09/12/11 CET
If you have a patient whose visual acuity (VA) is decreasing year by year due
Figure 1
The different types of free-radicals generated from
oxygen15
lipid-containing residues of lysosomal
digestion). Of note, the accumulation of
to age-related macular degeneration (AMD) and the hospital eye service
lipofuscin within the RPE cells increases
(HES) has told them that ‘nothing can be done’, what advice would you give
as a result of incomplete digestion of
to the patient? In addition to discussing lifestyle changes such as smoking
oxidatively
cessation, ultraviolet (UV) protection and accessing low vision services, if
appropriate, how many practitioners actively recommend the use of dietary
supplements? Hopefully, by the end of this article, many more will understand
the potential that nutritional supplements offer for this eye condition.
AMD is now the leading cause of
experiences with health professionals
blindness
world1
at the time of diagnosis because “they
and its prevalence is likely to rise
were not treated as a person”, making it
as a consequence of increasing life
more difficult to adapt to the condition.
expectancy.2 Indeed, in 1933 just 6% of
The
the registered population in England and
people were given more information
Wales had ‘senile macular degeneration’
about the disease and the potential
compared to nearly 50% in 1990.3 In the
prevention/treatment options for AMD,
UK, approximately 30,000 people are
they would be more likely to adjust to
registered blind or partially sighted every
their situation, and it would enable
year, half of whom will have AMD. With
them to deal with the condition and
respect to the visually consequential
ultimately have a better quality of life.
in
the
western
stage of the disease, it has been estimated
that 6-8% of people aged over 75 years
suffer from visual problems due to AMD.
If
macular
function
is
authors
believe
that
if
these
What happens at the macula in
AMD?
damaged
photoreceptor
outer segment membranes. In turn,
this yellow pigment then acts as a
chromophore, a compound which, when
irradiated with light of an appropriate
wavelength, emits an electron, thereby
generating
reactive
oxygen
species
(ROS). This provokes further oxidative
injury. Of interest, ROS production
(and, therefore, oxidative injury) peaks
at the macula, where AMD manifests.4
Unfortunately there is no treatment
that can restore vision in the dry, nonexudative form of AMD. For this reason
there is a lot of interest in trying to
prevent the disease from developing
in the first place. Risk factors such as
age, gender, family history (we now
know the genes responsible for AMD),
iris colour and refractive error are
all examples of non-modifiable risk
factors for AMD.6 However, there are
degraded,
The appearance of yellow-white lesions
the ability to read, drive a car, and
called drusen is usually the first clinical
even recognise familiar faces can be
manifestation
lost. Many studies have shown that
comprises a photoreceptor and axon-
the quality of life of these patients is
containing neurosensory layer with an
significantly diminished, and patients
underlying single-layer retinal pigment
lose their social independence.4 Indeed,
epithelium (RPE). The function of the RPE
it was reported that over 60% of people
is to nurture and remove waste products
Macular pigment
who were told ‘nothing can be done
from the neurosensory retina. AMD is
Macular pigment is yellow in colour and
about your macular disease’ suffered
characterised by loss of photoreceptors
is housed in the fovea, where we have
from anxiety and/or depression, and
and by RPE cell dysfunction, the latter
sharpest VA and colour appreciation
54 out of 1,421 people reported feeling
being largely attributable to an age-related
(it is found in the inner retinal layers
suicidal.5 The same study found that
accumulation
(yellow-
and the fibres of Henley).7,8 It is made
most patients reported unsatisfactory
brown pigment granules representing
up of three carotenoids (from a total of
of
of
AMD.
The
lipofuscin
retina
many modifiable risk factors that can
be controlled, which forms the basis of
preventative measures an individual
can
take.
Importantly,
smoking
cessation and diet are two important
modifiable
risk
factors
for
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AMD.
600 naturally occurring carotenoids)
segments are rich in polyunsaturated fatty
and these include lutein, zeaxanthin,
acids (PUFAs), such as docosahexaenoic
The correlation between AMD
and carotenoids
and
meso-
acid (DHA), compounds that represent an
The investigators of the Eye Disease
The density is at a
ideal substrate for oxidative damage.11,16
Case Control Study23 found that the
maximum at the centre of the fovea and
The macular pigment serves to combat
higher the levels of antioxidant micro-
central
zeaxanthin.
9,10
component
blue
nutrients, especially the carotenoids,
and zeaxanthin cannot be synthesised
light; it has peak absorption at 460nm
the more protection there is against
by the body and are therefore entirely
and a broad spectrum,
ranging from
neovascular AMD. However, it was
of dietary origin.12 Meso-zeaxanthin
zero to about 560nm.
The orientation
a later study24 that discovered that
is primarily formed in the retina
of macular pigment is optimised to
the highest correlation of disease
following conversion from lutein, but
enhance light absorption11 and because
prevention was with the intake of
is an important component of macular
of the way the macular pigment is
6mg per day of lutein and zeaxanthin,
pigment because of its unique central
distributed
which
location. It is the strongest antioxidant
cells, each cell screens other cells as
of the macular carotenoids and allows
well as itself. The macular pigment has
for
investigate which foods had the highest
this decreases peripherally.
11
Lutein
oxidative
stress
by
absorbing
17
through
photoreceptor
resulted
in
a
reduction
in prevalence of AMD by 43%.
The
authors
then
went
on
to
of
damaging
also been shown to have antioxidant
(blue)
light.13
capabilities, by itself donating electrons
amount of lutein and zeaxanthin,
Macular pigment is believed to have
to free radicals in order to stabilise them
and found that the consumption of
and thus prevent damage to RPE cells.
spinach in particular was associated
optimal
filtration
short-wavelength
a protective role in AMD mainly due
18
with a significantly reduced risk of
to its light-filtering and antioxidant
properties.
11,14
As the wavelength of
light in the visible spectrum is reduced
(i.e. shorter), retinal damage increases
exponentially.14
In
fact,
100x
less
energy is required to produce detectable
damage at 440nm than at 590nm. This
is known as the blue light hazard7
and retinal damage occurs due to the
AMD. Subjects in the study group that
Diet, plasma carotenoids and
macular pigment
Most
studies19,20
have
shown
had the highest spinach consumption
that
increasing dietary intake of fruits and
vegetables high in the carotenoids leads
had an 86% lower chance of AMD as
compared to the study group that had
the lowest spinach consumption.24
to an increase in concentration of lutein
in blood plasma. This relationship
The AREDs trial
is
that
In 2001, the Age-Related Eye Disease
production of free-radicals (hydrogen
measurements of such carotenoids in
Study (AREDS) was published, having
peroxide and singlet oxygen) (Figure 1).
the plasma can be used as an indicator
been conducted by the National Eye
Free radicals have one or more
of fruit and vegetable consumption and
Institute (NEI). This was a double-
unpaired electrons, making them have a
vice versa. Furthermore, dietary intake
masked,
strong tendency to find and pair with an
and serum carotenoid concentrations are
controlled trial of 4,757 subjects over
electron from substances such as lipids
positively related to a person’s macular
a period of five years. In brief, it was
(known as lipid peroxidation), proteins,
pigment level (this is not surprising
shown that supplementation with
carbohydrates and nucleic acid, resulting
given that macular pigment is entirely
vitamins C and E, beta-carotene, and
in damage to biological molecules. Free
of dietary origin).21 For example, in
zinc in combination resulted in a
radicals are also produced from oxygen
subjects who took 30mg of lutein per
25% risk reduction of progression to
metabolism, which is required for
day for 140 days, the serum levels of
advanced AMD. Of note, the AREDS
normal cell function and life (i.e. free
lutein increased from 0.13µg/ml to
did not supplement with any of
radical production cannot be avoided
0.93µg/ml within 20 days. The authors
the macular carotenoids, primarily
and is the “cost of living”). The retina
also found that macular pigment in
because these compounds were not
is ideally suited for the production of
the retina increased by 20-40%. As a
available in supplement form at the
free radicals, due to its high oxygen
result, the authors calculated a 30-40%
inception of that study. The study
demand, exposure to light, metabolic
reduction in blue light transmitted
groups
activities (such as RPE phagocytosis),
to
photoreceptors,
antioxidants (vitamin C, vitamin E
and its abundance of photosensitisers.
Bruch’s membrane and RPE – the
and beta-carotene), or antioxidants
Furthermore, the photoreceptor outer
tissues
plus zinc, or zinc alone, or a placebo.25
strong
the
enough
macular
usually
to
suggest
affected
in
AMD.
22
49
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randomised,
were
assigned
placebo-
to
taking
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risk of developing this condition, with
information of ways to help them reduce
the risk of this condition progressing
or
developing.
The
case
studies
below are in support of such a notion.
Case study one
50
A 64-year-old woman, who drove, did
voluntary work at the local hospice,
and enjoyed walking and gardening,
was seen for a routine sight test for the
Figure 2
Case study 1: macula appearance in September 2009 (see text for details)
first time in five years on 13/02/2009.
Her general health was good and the
09/12/11 CET
only medication she was taking was cocodamol for hip problems. Her mother
suffered from advanced (wet) AMD,
so she had a confirmed family history.
The patient used to smoke about 10
cigarettes per day from the age of
17 to the age of 55 years, but gave up
once her husband stopped smoking.
The patient reported that her diet had
always been good. On examination, she
was found to have soft confluent drusen
at the macula in both eyes (Figure 2).
Figure 3
Case study 1: macula appearance in March 2010 (see text for details)
Her best corrected vision at this stage
was RE: 6/6- and LE: 6/6+, whilst
there was corresponding distortion on
Amsler chart investigation. As a result,
this patient was referred to the HES,
who later confirmed that she had dry
AMD; she was discharged without
treatment or any recommendations on
lifestyle or nutrition to help prevent
the disease progressing.
The patient
conducted research on the Internet
and
read
may
help
that
taking
to
stabilise
supplements
the
AMD.
Since September 2009, this woman
Figure 4
Case study 1: macula appearance in March 2011 after intake of dietary supplements (see text for details)
had been taking a dietary supplement
The AREDS 2 is an ongoing multi-
the outcome of AREDS 2 (expected
(commercially known as Macushield).
centre
trial
at the end of 2012) and other clinical
On the 02/03/2010 this woman was
designed to evaluate the effect of
trials studying the macular carotenoids,
seen for a follow-up sight test at which
supplemental lutein and zeaxanthin
the authors feel that it is important
there was evidence of drusen resolution
(and/or omega-3) with respect to the
that eye care professionals furnish
(Figure 3). Importantly, the patient’s
progression of AMD. While we await
patients with AMD, and individuals at
best corrected vision at this examination
randomised
controlled
containing
zeaxanthin
the
and
carotenoids
lutein,
meso-zeaxanthin
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was RE: 6/6 and LE: 6/6, and there was
no distortion reported on Amsler chart
investigation. At the most recent eye
examination on 08/03/2011, the patient’s
best corrected vision was RE: 6/5 and
LE: 6/5, and the drusen has resolved
further, as shown in Figure 4. The
51
patient herself felt that her “vision had
noticeably improved”. In this particular
case, the only variable that had changed
in the past two years was the intake of
supplementation
every
day.
Case study two
Figure 5
Case study 2: macula appearance in 2008 (see text for details)
09/12/11 CET
dietary
This 64-year-old woman who was a
retired classroom assistant had always
had good general health, had never
smoked and had not been on any longterm medication. She was diagnosed
with dry AMD in 2004. She then
presented for a sight test in 2008, and
was referred to the HES for suspected wet
AMD in the LE (Figure 5). Her VA was
RE: 6/10 and LE: 6/10. The HES planned
to
administer
Lucentis
injections.
However, by the time the patient was
allocated an appointment, they noted
that the exudation had ceased and the
Figure 6
Case study 2: macula appearance in March 2011 after intake of dietary supplements (see text for details)
patient was therefore discharged. At this
moment in time the patient decided to
Discussion
start taking 20mg of lutein every day.
In both of the cases reported here, the
the
Prior to this, the patient had been taking
drusen was initially of the soft confluent
carotenoids against AMD. These case
generic
supplements.
type, which is more likely to progress
studies, combined with findings emerging
multi-vitamin
are consistent with research that suggests
potential
protection
of
macular
In January 2010 her VA in her right
to advanced AMD. Since taking dietary
in the past two years, contribute to the
eye had improved to 6/7.5 and there
supplements containing the macular
evidence around AMD and carotenoids.
was a further improvement to 6/6-
carotenoids over a relatively short time
However, the results of gold standard
1 when she was reviewed again in
period (18-24 months), there are notable
clinical studies are required, and are
March 2011; there was a corresponding
areas of the macula where the drusen has
awaited, in order to gain further support
reduction in macular drusen too, as
completely resolved, whilst in other areas
for the use of dietary supplements for
shown in Figure 6. The LE VA has not
it has become discrete and hard, which is
AMD, but there is growing evidence and
improved even though there is drusen
less likely to progress to advanced AMD.
it is, perhaps, only a matter of time. At
resolution. This woman had herself
Many optometrists will be familiar with
present, eye care professionals have a
noticed that her vision iwas getting
fundus images showing progression
duty to make informed recommendations
better, and she reported that she could
of AMD but discovering two cases of
for patients at risk of AMD, regarding the
now do cross stitching again. She also
AMD getting better is quite remarkable!
use of appropriate dietary supplements
always made an effort to wear sunglasses
for AMD (e.g. a supplement containing
when outdoors and would continue to
Conclusion
the macular carotenoids), along with
take macular carotenoid supplements.
The case studies reported in this article
positive lifestyle changes (e.g. smoking
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is also Chair of the Dudley LOC and
Howard Fellowship by the Howard
protection). So the next time you
a council member for the College of
Foundation at Cambridge University,
see a patient with AMD, will you
Optometrists, representing the West
UK. He is a key opinion leader on the
consider
and
weight
control
authors
and
carotenoids
Midlands. Dr John Nolan is a senior
subject of macular pigment and AMD,
supplementation?
scientist and director of the Institute
and has been invited to speak at over
certainly
of Vision Research and the Macular
40 international scientific conferences
Pigment Research Group (MPRG). His
and has published over 30 scientific
PhD study, entitled “Determinants of
peer-reviewed publications on the topic.
recommending
dietary
These
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cessation,
52
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will.
About the authors
Shamina Asif is an optometrist working
macular pigment in healthy subjects”,
at the Merry Hill Centre, Dudley. She
was the largest cross-sectional study
References
was awarded an academic prize for
of its type in the world. Dr Nolan
See
the best mark in her Elective Studies
was awarded a Fulbright scholarship
clinical/index. Click on the article title
looking at AMD and nutrition. She
and in May 2010 he was awarded a
and then download “references”.
Module questions
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Course code: C-17541 O
1. Which of the following foods has the highest amount of lutein/
zeaxanthin?
a) Broccoli
b) Brussel sprouts
c) Spinach
d) Coriander
2. Why were lutein and zeaxanthin not included in the AREDS trial?
a) There was no known link between lutein/zeaxanthin and AMD
prevention
b) They were too expensive to use
c) Lutein and zeaxanthin had not been discovered at the time
d) They were not readily available in supplement form
3. The peak wavelength of absorption of macula pigment is:
a) 460nm
b) 490nm
c) 520nm
d) 560nm
4. Which of the following is NOT a non-modifiable risk factor for AMD?
a) Iris colour
b) Age
c) Gender
d) Diet
5. How does the macula pigment protect against AMD?
a) It causes lipid peroxidation
b) It stabilises free radicals by donating electrons
c) It reduces oxygen consumption in the retina, reducing free radical production
d) Its absorption spectrum peaks at 560nm hence absorbing the blue light hazard
6. What does the macula pigment consist of?
a) Lutein and meso-zeaxanthin
b) Beta-carotene, lutein and zeaxanthin
c) Lutein, zeaxanthin and meso-zeaxanthin
d) Meso-zeaxanthin, lutein and beta-carotene
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