Abstract
purpose. Increasing evidence implicates macular pigment in protecting the retina
and retinal pigment epithelium from light-initiated oxidative damage.
Little information, however, is available regarding “average”
levels of macular pigment in the general population. This study was
designed to assess macular pigment in a high-light environment and to
determine what personal characteristics influence macular pigment
density in that sample.
methods. Macular pigment optical density was measured psychophysically using a
1°, 460-nm test stimulus. Personal data were collected using a
questionnaire.
results. 217 subjects (79 men, 138 women) were recruited from the Phoenix
metropolitan area (age range = 17–92 years). The average macular
pigment density was 0.22 ± 0.13. There was a slight tendency for
macular pigment density in this sample to decline with age (r =−
0.14, P < 0.02). Average macular pigment density
was significantly lower in women versus men (P <
0.05), lower in individuals with light-colored irises versus
dark-colored irises (P < 0.009), and lower in
heavy smokers compared to light (P < 0.0045) and
never (P < 0.034) smokers.
conclusions. Macular pigment density was lower than average levels obtained from the
Northeast but similar to average values obtained in a recent study of
adults recruited from Indianapolis. Consistent with past studies, MP
density was 13% lower in women and 18% lower in individuals with
light- versus dark-colored irises. The relation of smoking to macular
pigment density was only significant for those current smokers who
smoked more than 10 cigarettes per day (about a 25% reduction). The
large number of individuals in this sample with low macular pigment
density motivates the need for population-based assessment of the
possibly poor nutritional state of the average American’s
retina.
Concentrated within the inner layers of the primate fovea is a
yellow pigment that is derived from the dietary carotenoids lutein and
zeaxanthin. Two main hypotheses have been advanced to account for the
presence of these macular pigments in primate retinas. The“
protection hypothesis” proposes that macular pigment (MP) protects
the retina and retinal pigment epithelium from oxidative damage leading
to age-related loss of function and macular disease.
1 2 Although direct evidence for this hypothesis is difficult to obtain and
would require longitudinal data, a variety of indirect evidence is
available to support this hypothesis. For example, epidemiologic
evidence has indicated that high intake of lutein and zeaxanthin and
high blood levels are related to reduced risk of age-related macular
degeneration (AMD).
3 4 5 Damage leading to geographic AMD
tends to be paracentral, with a relative sparing of the retinal area
where MP can be found in its highest concentration,
6 and
monkeys raised on carotenoid-depleted diets show macular
anomalies.
7 There are also directional parallels between
factors influencing the risk of AMD
1 and factors that tend
to predict individual differences in MP density. Lower MP density tends
to be related to factors that may increase risk of AMD (e.g.,
smoking,
8 light irises,
9 female
gender,
10 ), whereas higher MP density tends to be related
to factors that may decrease risk of AMD (e.g., improved diet, male
gender, dark irises). Finally, individual differences in MP density are
related to individual differences in age-related losses in visual
sensitivity, with those having the lowest MP density having the highest
amount of age-related loss.
11 Although the confluence of
this evidence is compelling, the evidence is largely correlational in
nature, and the magnitude of the effect is far from clear.
The other main functional hypothesis for MP is based on the possibility
that the pigments improve visual resolution. The “acuity
hypothesis” proposes that MP improves acuity by absorbing short-wave
light, which is easily scattered and poorly focused.
12 The
acuity hypothesis is based on the problem that the optics of the eye
create rather severe chromatic aberrations in the very spectral region
that MP maximally absorbs (ca. 400–490 nm).
13 The
possibility that MP improves visual performance is consistent with
preliminary data showing that supplementing the MP carotenoid lutein
(L) may improve visual function. For example, Zorge et
al.
14 recently reported that L supplements significantly
improved visual function (e.g., acuity) in 20 patients with congenital
retinal degenerations, such as retinitis pigmentosa. Similarly,
Richer
15 has shown that dietary supplementation of
patients with AMD (
n = 14) caused dramatic improvements in a
number of visual function tests (e.g., 92% had significant
improvements in contrast sensitivity). Richer supplemented using 5
ounces of spinach, which he suggested increased the patient’s MP
density,
16 leading to the improvements in visual function.
Such studies have not addressed whether MP is improving the optics of
the eye (the acuity hypothesis) and/or treating the underlying disease
(the protection hypothesis). No direct empiric test of whether MP
actually improves acuity is yet available.
Based on the available evidence, it is reasonable to conclude that MP
does serve some function within the eye rather than simply being an
imperfection in the eye’s optics. Thus, the fact that MP density
varies so dramatically between individuals is also meaningful. If this
premise is correct, then information regarding “average” levels of
MP density in the general population is needed. Although a number of
large epidemiologic studies are available showing average levels of
dietary carotenoid intake
17 18 and blood levels of lutein
and zeaxanthin,
19 few large studies are available showing
variation in retinal carotenoid levels within the normal population.
The lack of a representative database is at least partially due to the
advanced optics required to measure MP in the traditional manner (e.g.,
Maxwellian view optical systems). This has limited study of the MP
carotenoids to smaller samples that may not be representative of the
larger population. The recent availability of simplified optics for
measuring MP in natural view
20 has provided the means for
larger studies on MP density to be conducted. In the present study, we
report MP density in a large urban sample recruited from the Southwest
region of the United States.
MP optical density was measured psychophysically using flicker
photometry (for a review of this procedure and the underlying
assumptions, see Snodderly and Hammond
21 ). Only the right
eye of each subject was measured. A circular test stimulus was
presented near the center of a 6°, 1.5 log Td, 470-nm circular
background. The size of the test stimulus was 1°. We also measured MP
density in some subjects (
n = 171) with a 2° test and a
2° annular field to check within-session consistency (as described
more fully later). The wavelength composition of the test stimulus
alternated between a 460-nm measuring field (peak MP absorbance) and a
570-nm, 1.7 log Td reference field (minimal MP absorbance). The
measuring and reference fields were superposed and presented out of
phase at an alternation rate of 11 to 12 Hz in the foveal condition and
6 to 7 Hz in the parafoveal condition. Subjects adjusted the radiance
of the 460-nm measuring field to achieve minimal flicker with the 570
nm reference. This measurement was done in the fovea (where MP is the
most dense) and 4° in the parafovea (where light absorption by MP is
negligible).
22 23 A tiny (5 minute) opaque fixation point
was located on the left edge of the background and subjects fixated
this point when making the parafoveal measurement. Subtracting the
foveal from the parafoveal log sensitivity measurement yields an
optical density measure of MP.
Light for the 10° background was produced by three LEDs (packed
tightly in a triangular array) with peak energy at 470 nm and
half-widths of approximately 20 nm. Light for the 570-nm reference
field was produced by an LED with peak energy at 570 nm
(half-width = 20 nm). Light for the 460 nm measuring field was
produced by two LEDs with peak energy at 458 nm (half-width = 20
nm). Light from the LED sources was collimated with planoconvex lenses
and was then passed through polycabonate diffusers (high-efficiency,
holographic type; Physical Optics Co., Torrance, CA), which
served essentially as back projection screens.
The size of the background and test stimulus was defined by circular
apertures (constructed by computer-generated images exposed on
high-density, photographic mylar film) placed after the collimating
lenses. The background and test stimuli were then combined and
reflected to the subject by a 2-inch beamsplitter whose front surface
was located 16 inches from the subject’s eye. The entire optical
system was contained in a rectangular, black Plexiglas box. One side of
the box contained a one-inch hole centered on the subject’s optical
axis through which the stimulus could be viewed. Head alignment was
accomplished by the use of an adjustable head and chin rest assembly
and, when properly aligned, the subject viewed the hole in the box as
slightly larger and concentric with the background field.
Stimuli were calibrated using a photocell (PIN-10, UDT Sensors,
Inc., Hawthorne, CA). The LEDS were driven by a constant
current power supply. Radiance variation was achieved by varying the
frequency of a 1.5-msec pulse over a range of 300 to 300,000 Hz. Our
calibration of the high-frequency pulse rate shows that the frequency
delivery is nearly perfectly proportional to the radiance output. Thus,
MP density values could be derived by simply calculating the log ratio
of the frequencies of the 460-nm measuring field at the foveal and
parafoveal eccentricities, respectively.
The apparatus used for the MP measurement delivered the stimulus in
natural view, but used a stimulus configuration that was similar to
configurations used in past studies, where the stimulus was presented
in Maxwellian view.
8 9 10 11 16 22 24 Recent data on 32
subjects (age range = 16–60 years) has shown, however, that MP
density measured in natural view and with slight differences in
stimulus configuration (e.g., this study used a 4° rather than a 6°
parafoveal reference) provides the same values as MP measured in
Maxwellian view (range of MP values = 0.0–0.60).
20 As an additional check, we measured the MP density of two highly
experienced investigators using the Maxwellian systems in
Boston
8 11 16 and Phoenix
20 and the natural
view optical system used in the present study in Phoenix and a similar
system in Indianapolis.
25 The different systems yield the
same values at the different sites (0.40 ± 0.05 and 0.64 ±
0.03).
Given the reliability of the MP measurement technique,
22 we elected to limit subject assessment to only one experimental
session. Eight subjects, however, with no previous experience with
psychophysical tasks, were measured in 10 separate sessions spaced over
2 to 4 weeks to check the reliability of our current instrument. The
range of MP values across experimental sessions was 0.07 for the best
subject and 0.27 for the worst subject (average range = 0.166).
The values had strong central tendencies, however, and were reliable
(Cronbach’s α = 0.97).
Because the spatial density distribution of MP is well
known,
22 26 subject accuracy can be checked by changing
the spatial configuration of the stimulus and checking the resultant
value against the known spatial density distribution of the pigments.
To this end, we measured MP density using a 2° solid test field and a
2° annulus (see
Table 1 ). Past work
22 has suggested that
MP density declines exponentially when it is measured at increasing
distances from the center of the fovea. Consistent with this
prediction, the average MP density at 2° (0.13) is what would be
predicted based on the average MP density value at 1° (0.22). The
edge hypothesis
24 predicts that when MP density is
measured using flicker photometry that the derived optical density
value is largely determined at the edge of the flickering test stimulus
rather than averaged across the entire test field. Although the average
MP density obtained with the 2° annulus (0.10) was slightly lower
than the value obtained with the solid 2° field (0.13), the
correlation was high (
n = 171,
Y = 0.007 +
0.71
X,
r = 0.80). Consistent with past
studies,
22 these analyses suggest that the technique we
used for measuring MP density provided reliable data.