Download Changes in spatial extent and peak double optical density of human

A. M. G. Baptista and S. M. C. Nascimento
Vol. 31, No. 4 / April 2014 / J. Opt. Soc. Am. A
A87
Changes in spatial extent and peak double optical
density of human macular pigment with age
António M. G. Baptista* and Sérgio M. C. Nascimento
Center of Physics, University of Minho, Campus de Gualtar, 4715-303 Braga, Portugal
*Corresponding author: [email protected]
Received September 30, 2013; accepted December 6, 2013;
posted December 13, 2013 (Doc. ID 198611); published January 21, 2014
The purpose of the present work was to estimate the changes in spatial distribution and optical density of macular
pigment (MP) with age. A fundus imaging system with high spatial and spectral resolution was adapted to form an
indirect ophthalmoscope. The double optical density at 490 nm of the MP as a function of the location in the retina
was obtained for 33 healthy subjects (ages: 21–60 years). There was an increase in spatial extent and decrease in
double optical density with age. Furthermore, the spatial distribution of MP showed central areas with irregular
shapes and a tendency toward asymmetry. © 2014 Optical Society of America
OCIS codes: (330.4460) Ophthalmic optics and devices; (330.6100) Spatial discrimination; (330.6180)
Spectral discrimination; (330.7323) Visual optics, aging changes; (330.7327) Visual optics, ophthalmic
instrumentation.
http://dx.doi.org/10.1364/JOSAA.31.000A87
1. INTRODUCTION
The macular pigment (MP) is a yellow pigment found in the
human fovea in both the inner and outer layers of the retina,
and located along the axons of the cone photoreceptors [1].
It is mainly composed of two xanthophylls, lutein and
zeaxanthin [2]. MP has a peak absorption wavelength at
460 nm but nearly no absorption of light at wavelengths longer
than 530 nm [3,4]. The function of MP is not fully understood
but appears to be fundamental for maintaining normal retinal
function. It is thought to play an important role in the protection of photoreceptors from short-wavelength radiation
damage and as an antioxidant [5]. It may serve to reduce
the effects of chromatic aberration and light scatter on visual
performance [6]. There is also evidence that low levels of MP
may be related to a higher risk of developing age-related
macular degeneration [7–9]. Macular pigment optical density
(MPOD) has been demonstrated to increase after diets rich in
zeaxanthin and lutein [10–16].
Measurements of MPOD as a function of age have been carried out using different techniques. Some studies using fundus
reflectance spectroscopy found that MPOD for older subjects
was higher than that for younger subjects [16–18] while others
have found no age-dependence [19–21]. Similar variability has
also been obtained in psychophysical studies, where an agerelated decline was found in some studies [8,22–25], but not
others [15,26,27]. The effect of age on MP spatial distribution
has been recognized [16,19]; however, this has generally not
been analyzed as an important variable of MP. The precise
characterization of the optical density of MP and, in particular,
its spatial extent, is still an open issue.
The amount and distribution of MP have been assessed by
fundus reflectance spectroscopy. This optical approach is
based on models considering the physical interactions (e.g.,
absorption, scattering, and reflectance) between light and ocular structures as a function of wavelength [28,29]. The fundus
1084-7529/14/040A87-06$15.00/0
imaging systems based on lasers, such as the scan laser ophthalmoscope, or wavelength filters, such as a beam splitter
combined with narrow band-path filters, are restricted to
the number of wavelengths that can be used [11,30]. The multispectral imaging system may overtake this restriction because
the filter can be tuned to a wide range of wavelengths. Several
groups in the last decade have used this technique to study
retinal structures, including macular pigment [31,32].
The main purpose of the present work was to estimate the
changes in spatial distribution and peak double optical
density of MP with age from measurements made with a high
spatial resolution, multispectral system, adapted to an indirect
ophthalmoscope.
2. METHODS
A. Apparatus
The imaging system was based on an indirect ophthalmoscope, adapted with a xenon lamp coupled to a fast tunable
liquid–crystal filter (VariSpec, model VS-VIS2-10HC-35-SQ,
Cambridge Research & Instrumentation, Inc., MA, USA),
and with a low-noise Peltier-cooled digital camera
(Hamamatsu, model C4742-95-12ER). The lamp was a
150 W xenon short-arc lamp (Hamamatsu, type L2274) with
a stable light emission from 400 to 800 nm, and was provided
with a stabilized power supply (Hamamatsu, type C2577) for a
stable light flux output. The liquid–crystal filter could be electronically tuned to any wavelength in the range from 400 to
720 nm with a spectral resolution of 1 nm, and had a nominal
FWHM of 10 nm at 550 nm. The CCD camera had a spatial
resolution of 1344 H × 1024 V pixels, 6.45 μm × 6.45 μm
pixel size, 12 bit output. A 2 × 2 binning acquisition mode
was used for increased sensitivity. The area of the retina illuminated by the system was of about 20 deg visual angle.
The light uniformity was tested against a BaSO4 surface
and the variations were less than 12% between the extremes
© 2014 Optical Society of America
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J. Opt. Soc. Am. A / Vol. 31, No. 4 / April 2014
A. M. G. Baptista and S. M. C. Nascimento
of the observation field, which was about 11 deg. The estimated
spatial resolution at the retina was about 1 min ×1 min. The
light reflected at the cornea and lens was minimized by separating the entrance from the exit pupil of the system.
B. Procedure
Subjects were dilated with tropicamide and phenylephrine to
obtain pupil diameters larger than 7 mm. To reduce the effect
of the visual pigments as a variable parameter, the fundus was
bleached immediately before image acquisition using a bright
white light source (halogen lamp with a correlated color temperature of 3150 K) of 5.57 log and lasting 80 s. This bleaching
procedure removes more than 90% of the visual pigments [33].
Pixels were converted to visual angle using pairs of images,
acquired when the subject fixated at target points separated
by 2 deg.
For each subject, two images of the retina were sequentially
acquired, corresponding to retinal illuminations with monochromatic light of 490 and 540 nm. Let each of these images
be represented by Sλ, where λ is the wavelength of the illumination. The second peak of MPOD (at about 490 nm) was
selected instead of the first (at about 460 nm), to minimize the
effect of eye movement by reducing total acquisition time (by
lowering ocular media absorption) to about 2 s. The remaining
effects of small eye movements were compensated for by
aligning the retinal images obtained for the two wavelengths,
with retinal blood vessels used as references.
For each Sλ, corresponding white S w λ and dark S d λ
references were also acquired. S w λ was obtained using an
artificial eye with a power of 60 diopters and with its fundus
coated with fresh BaSO4 . S d λ was obtained with the same
device coated with a dark coating. The three images were
acquired with the same exposure times for each wavelength.
[19], was used here to obtain the double-passed optical density of MP δ at 490 nm. The pigments of the absorbing layers
correspond to ocular media, macular pigment, and melanin
with optical densities D1 , D2 , D3 , respectively, and the reflectance layer corresponds to the retinal pigment epithelium
(RPE) with reflectance r and assumed independent of the
wavelength and retinal position. The contributions of the
ocular media were also assumed independent of the retinal
position.
Applying the Beer Lambert law to the simplified model, the
eye reflectance Rλ can be expressed:
Rλ r × 10−2D1 λ2D2 λ2D3 λ :
Applying Eq. (2) to 490 and 540 nm, assuming D2 540 0
and defining 2D2 490 as δ:
δ log10
D. Computations
The reflectance factor of each pixel of the retina region was
estimated by
Rf λ Sλ − S d λ
:
S w λ − S d λ
1
1
− β log10
A;
R490
R540
(3)
where
β
D3 490
;
D3 540
(4)
and
D 490
A β− 1
2D1 540 1 − βlog10 r:
D1 540
(5)
As the reflectance factor Rf differs from the reflectance R
by a multiplicative constant k
δ log10
C. Subjects
A total of 33 Caucasian subjects were selected from a group of
volunteers. The exclusion criteria were narrow angle between
cornea and iris, tonometry repeatedly over 22 mmHg, ocular
diseases, heart problems, refractive errors higher than 3
(positive or negative) diopters or astigmatism higher than
1.5 diopters, cloudy ocular media, fixation or behavioral problems, ptosis, food supplements, particular diets such as vegetarian, and smokers. The 33 subjects were divided into 3
groups: group A with 12 subjects (10 female and 2 male) with
a mean age of 22.3 years and range of 21–25 years; group B
with 12 subjects (2 female and 10 male) with a mean age of
36.0 years and range of 30 to 45 years; and group C with 9
subjects (6 female and 3 male) with a mean age of 55.2 years
and range of 50 to 60 years. Informed consent was obtained
from all participants and the research was conducted according to the guide lines promoted by the Declaration of Helsinki.
(2)
1
1
− β log10
A B;
Rf 490
Rf 540
(6)
where
1
1
B log10 − β log10 :
k
k
(7)
Taking into account the reflectance factor obtained in the
peripheral retina x0 ; y0 , where δ 0, and assuming that A
and B are independent of the retinal position, then
δx;y log10
1
1
− β log10
Rf x;y 490
Rf x;y 540
− log10
1
Rf x0 ;y0 490
− β log10
1
Rf x0 ;y0 540
;
(8)
where β is assumed to be 1.12 [34].
The spatial distribution δx;y was derived for each pixel
using Eq. (8). For Rf x0 ;y0 , the average over an area of about
0.5 deg2 centered on a point at an eccentricity of about 5
degrees, where MPOD is negligible, was used [35–37]. To minimize pixel noise, a low pass filter was applied to the data
resulting from Eq. (8).
(1)
The model of van Norren and Tiemeijer [28], simplified by
considering three absorbing layers and one reflective layer
3. RESULTS
Figure 1 shows macular pigment distribution for two subjects.
The retinal area represented is about 11 deg. Qualitatively, it
A. M. G. Baptista and S. M. C. Nascimento
Fig. 1. Macular pigment distribution for two subjects (S 1 and S 2 ).
can be seen that the distributions show higher values in a central area, declining to around zero in the periphery; also, the
distributions are asymmetric and have central areas with
irregular shapes. It can also be seen that low values extend
laterally over the limits of the observation field. Data for
the other observers show similar features.
Vol. 31, No. 4 / April 2014 / J. Opt. Soc. Am. A
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The mean peak double optical density (optical density corresponds to 0.5 × δ) of MP δ standard deviation was
0.23 0.07, 0.25 0.07, and 0.16 0.05, ranging from 0.13–
0.40, 0.16–0.36, and 0.08–0.22 for groups A (the youngest),
B and C (the oldest), respectively. After the ANOVA oneway test (df 2, F 6.253, p 0.005), multiple comparisons
(Tukey) between groups showed statistically significant
differences between the groups A and C (p 0.049) and
groups B and C (p 0.004).
To characterize the spatial distribution of the MP, the
FWHM of horizontal and vertical profiles was computed for
each subject. To specify further the asymmetries of the distributions, a rectangle of a · b dimensions enclosing the section
at half-maximum was obtained. Figure 2, resulting from connecting 377 points between 3 deg with straight lines, shows
the vertical and horizontal profiles for double optical density
and section at half-maximum, within the rectangle a · b for the
two subjects. Table 1 lists mean values of vertical and horizontal FWHM, the standard deviations (SD), and maximum–
minimum range for each age group. Table 2 shows similar data
for a and b.
For all age groups, considerable inter-individual variability
(min, max, and SD) was found both in the values of the FWHM
and in the sizes a and b. On the other hand, the distributions
Fig. 2. Vertical and horizontal profiles and respective section at half-maximum, within the rectangle a · b for two subjects (S 1 and S 2 ).
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J. Opt. Soc. Am. A / Vol. 31, No. 4 / April 2014
A. M. G. Baptista and S. M. C. Nascimento
Table 1. FWHM (deg visual angle) Data for the
Three Age Cohorts
Group
Mean
Min
Max
SD
FWHM (horizontal meridian)
1.75
3.40
0.47
1.27
3.80
0.69
2.29
5.01
0.88
FWHM (vertical meridian)
2.30
1.73
2.81
0.36
2.19
0.96
3.10
0.62
3.14
1.58
4.54
0.97
A
B
C
2.64
2.55
3.26
A
B
C
ANOVA
df 2
F 3.139
p 0.058
df 2
F 6.092
p 0.006a
Statistically significant differences (p < 0.05)
a
Table 2. MP Distribution (deg visual angle)
in Terms of Enclosing Rectangle a · b for
the Three Age Cohorts
Group
Mean
A
B
C
2.75
2.72
3.65
A
B
C
2.48
2.35
3.39
Min
Max
a (horizontal)
1.80
3.54
1.27
3.84
2.56
5.32
b (vertical)
1.80
3.11
1.04
3.46
2.25
4.83
SD
ANOVA
0.53
0.74
0.94
df 2
F 5.083
p 0.013a
0.45
0.69
0.92
df 2
F 6.742
p 0.004a
Statistically significant differences (p < 0.05)
a
are clearly asymmetric, with larger extent in the horizontal
direction than in vertical direction. More than 87% of the
subjects present a (horizontal) larger than b (vertical).
Inter-group comparisons, after the ANOVA one-way test
(Tables 1 and 2), showed statistically significant differences
between groups A and C and between groups B and C, for
vertical FWHM and sizes a and b (Tukey, all p ≤ 0.024).
4. DISCUSSION
The optical and antioxidant properties of MP play an important role in maintaining the health and function of macula
through life. Quantification of MP levels and distributions
might help, for example, to identify individuals potentially
at risk for visual disability from age-related macular degeneration [5]. This work measured MP distributions for three age
groups using high spatial resolution. Large inter-subject variability in terms of peak density and spatial distribution was
found. Even so, there were significant differences in peak densities at 490 nm between the oldest group and the other two
groups, A and B, with the former showing smaller values.
Moreover, a clear asymmetry was found for the horizontal
and vertical directions, with a larger extent in the horizontal
direction. Generically, the effect of aging was found significant in both directions, revealing a larger spatial extent for
the older group.
Studies of macular pigment using fundus reflectance spectroscopy have produced values for MPOD (MPOD 0.5 × δ)
varying from 0.13 [38] to 0.54 [29]. High inter-study variability
is also found with psychophysical and auto-fluorescence
techniques, where values from 0.21 [39] to 0.87 [40] and from
0.22 [41] to 0.48 [17], have been recorded, respectively. The
range of values obtained in this work are similar to other
reflectance studies [17,19,41,42] and, in particular, to a recent
study using a similar technique, which obtained 0.15 0.05
for 6 subjects with a mean age 32.8 12.1 [32] (it should
be emphasized that computations here were carried out to
obtain MPOD at 490 nm rather than at the usual 460 nm,
where the 490 nm has values about 17% less than that at
460 nm [4]; thus, the corresponding scaling has to be applied
for comparison).
A decrease in MPOD with age was also found by a previous
study [41] using reflectance spectroscopy; however, in comparing the reflectance data with the auto-fluorescence data,
they attributed this decrease to reflectance artifacts caused
by the lens and the inner limiting membrane. Chen and
colleagues [19], using reflectance spectroscopy and the same
optical model as that used here, did not find any significant
variation in MPOD for older subjects. Similar conclusions
were obtained by Berendschot and van Norren [21]. On the
other hand, according to Pipis and colleagues, also using
reflectance spectroscopy, MPOD appears to increase with
age [16].
The values for the FWHM (horizontal meridian) obtained by
reflectance spectroscopy ranged from about 2.4 deg [36,38] to
3.2 deg [19]. The mean value obtained in this work of 2.8 deg is
in good agreement with these studies. The present work
showed that, in more than 87% of the subjects, the spatial
extent of MP in the horizontal meridian is larger than in
the vertical meridian. A slight tendency toward this asymmetry was also found by others [36,43]; although not by Bour and
colleagues [38], who found no substantial deviation from
circular symmetry in young subjects. In this study, the asymmetry in MP spatial distribution was further demonstrated by
an irregular topography and by the fact that, for some subjects, low values of δ extend laterally over the limits of the
observation field. Furthermore, macular pigment appears to
form more eccentric profiles with increased age [16].
The differences in spatial distribution between the oldest
group and the other two groups, corresponding to an increase
in spatial extent with age, were also found by Chen and colleagues [19] for the horizontal meridian.
Possible factors other than age effects for these changes,
both in the amount and distribution between studied populations, are diet and lifestyle [44,45].
The comparison between the fovea and peripheral retina
minimizes the effect of the background noise and avoids
the use of pigment density and RPE reflectance values from
the literature. However, MPOD seems to have small values at
6–8 deg, which could contribute to an underestimation of the
MPOD and the FWHM, since it was assumed to be zero at
5 deg [46,47]. The model applied here did not consider the
effect of pre-retinal and intra-retinal scatter, which again
might underestimate the MPOD and the FWHM [48]. However,
the increase in spatial extent with age and the relation between MP distribution in the horizontal and vertical meridians
is independent of these approximations. The remaining visual
pigment and possible light gradients in fundus illumination
could also introduce artifacts not considered in the present
study. Another factor that could influence the results from
fundus reflectance spectroscopy is that longer wavelengths
penetrate the retinal tissue to greater depths than do
shorter wavelengths [49,50]; therefore, the MP could not be
A. M. G. Baptista and S. M. C. Nascimento
completely revealed by short wavelength light. Thus, using
490 nm instead of 460 nm for imaging could be more effective
for MP study.
ACKNOWLEDGMENTS
This work was supported by the Center of Physics of Minho
University, Braga, Portugal. The empirical data analyzed in
this paper was reported in part at the 18th Symposium of
International Colour Vision Society. We are grateful to Alberto
J. Díaz-Rey for clinical assistance.
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