Acquired macular pigmentation. Macular amyloidosis.
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Macular pigment (MP) is composed of the two dietary carotenoids lutein (L) and zeaxanthin (Z), and is believed to protect against age-related maculopathy (ARM). This study was undertaken to investigate MP optical density with respect to risk factors for ARM, in 828 healthy subjects from an Irish population. MP optical density was measured psychophysically using heterochromatic flicker photometry, serum L and Z were quantified by HPLC, and dietary intake of L and Z was assessed using a validated food-frequency questionnaire. Clinical and personal details were also recorded, with particular attention directed towards risk factors for ARM. We report a statistically significant age-related decline in MP optical density (r2=0.082, p<0.01). Current and past smokers had lower average MP optical density than never smokers and this difference was statistically significant (p<0.01). Subjects with a confirmed family history of ARM had significantly lower levels of MP optical density than subjects with no known family history of disease (p<0.01). For each of these established risk factors, their statistically significant negative association with MP persisted after controlling for the other two, and also after controlling for other potentially confounding variables such as sex, cholesterol, dietary and serum L (p<0.01). In the absence of retinal pathology, and in advance of disease onset, the relative lack of MP seen in association with increasing age, tobacco use and family history of ARM supports the hypothesis that the enhanced risk that these variables represent for ARM may be attributable, at least in part, to a parallel deficiency of macular carotenoids.
We built a new macular pigment reflectometer (MPR) for fast and objective measuring of the optical density of macular pigment in the human eye, using the undilated eye. The design is based on the spectral reflectance from a spot of white light at the fovea. To evaluate its performance, we measured the macular pigment of 20 healthy subjects, ages 18 to 79 years, under four conditions: (1) natural pupil in the dark, (2) natural pupil with dim room light, (3) dilated pupil in the dark, and for comparison with a different technique, (4) heterochromatic flicker photometry (HFP) in dim room light with natural pupil. Condition 1 was repeated in a subset of 10 subjects after an interval of at least 3 days. Data analysis with a model of reflectors and absorbers in the eye provided the density of the macular pigment in conditions 1 to 3. Dim room light and pupil dilatation had no influence on measured density. Mean within subjects variation was typically 7%. Mean difference between test and retest after at least 3 days was 1%. Correlation between MPR and HFP was r=0.56 (p=0.012). Mean within subjects variation with HFP was 19%. The new instrument holds promise for specific applications such as epidemiological research.
The present concepts of the pathogenesis of AMD include cumulative light damage by oxidative processes in the macular photoreceptors as environmental co-factor for the development of AMD. The direct causative connection of this hypothesis has still to be established but wide circumstantial evidence from epidemiological and basic scientific investigations are strongly supportive. Macular pigment consisting of lutein and zeaxanthin through there ability to filter light and by direct antioxidative properties, has been proposed as the most effective protective factor in the central retina ("natural sun glasses") and could be important to reduce light induced oxidative retinal damage. The observation, that with age and especially in eyes with AMD lower concentrations of macular pigment could be found, can be interpreted that low macular pigment concentrations may be associated with higher risk for AMD. Through dietary intake and eventually with supplementation the concentration of macular pigment can be increased, and analysis of the correlation between macular pigment and AMD may be important to characterise a possible influenceable AMD risk factor.
AIM: Macular pigment (MP) is composed of two hydroxycarotenoids contained within the photoreceptors and the axons of the central neurosensory retina, with peak concentrations in the Henle layer. A full thickness macular hole (FTMH) is characterised by absence of all retinal layers in an area centred at the former centre of the fovea. The authors report the results of a study designed to investigate MP levels in patients following successful FTMH surgery, using Raman spectroscopy, and to correlate these findings with functional and topographic outcomes. METHODS: The following details were recorded for 12 eyes of 12 patients following successful closure of a FTMH: best corrected visual acuity; macula threshold test, fixation, fundus photography, and macular pigment levels using Raman spectroscopy. High resolution imaging of the retina using optical coherence tomography (OCT) was performed in nine of the 12 study eyes. RESULTS: Mean (SD) best corrected visual acuity was 0.6 (0.4) and improved significantly from preoperative levels. On macula threshold testing of the operated eye, a central scotoma was detectable in one eye only (8.3%). MP levels were demonstrable in 10 of the 12 study eyes following successful FTMH surgery. MP levels were higher in three study eyes, and lower in seven study eyes, when compared with the fellow eye. Of the three pairs of eyes where MP levels were greater in the study eye, macular pathology was present in two fellow eyes. CONCLUSIONS: The presence of MP was confirmed in the neurosensory retina of an anatomically closed FTMH in 10 of 12 study eyes, although the levels were lower than the fellow normal macula in nine of 10 cases. This suggests a good degree of physiological recovery of photoreceptors and their axons following successful FTMH surgery.
PURPOSE: To test the hypothesis that macular pigment reflects foveal cone function and possibly the presence of foveal cones in recessive Stargardt macular dystrophy. METHODS: Sixteen patients (32 eyes) diagnosed to have Stargardt macular dystrophy by clinical criteria were studied with a scanning laser ophthalmoscope (SLO) comparing argon laser blue (488 nm), green (514), helium-neon laser red (633 nm) and infrared diode laser (780 nm) images for the presence or absence of macular pigment in the fovea. Fifteen of the patients were screened for mutations in the ABCR gene. Eyes were graded into three categories: those without foveal macular pigment, those with partial pigment and those with normal amounts of macular pigment. These categories were compared with visual acuity determined by the Snellen chart. RESULTS: All patients with a visual acuity of 20/200 or worse had no macular pigment in the fovea. All patients with visual acuity of 20/40 or better had a normal amount of macular pigment in the fovea. Patients with partial macular pigment had intermediary acuity values except for two eyes, one with 20/20 and another with 20/200 acuity. Infrared light revealed more retinal abnormalities than blue light at early stages of the disease. CONCLUSION: Foveal macular pigment is related to foveal cone acuity in Stargardt macular dystrophy and may be a marker for the presence of foveal cones. Infrared light is a sensitive monitor of early Stargardt macular dystrophy.
Macular pigment (MP) has been suggested to have a protective role in age-related macular degeneration by reducing the amount of oxidative stress on the retina. MP levels peak at the foveal center, where it is found predominantly in the receptor axon and inner plexiform layers of the retina. The purpose of this study was to investigate the relationship between central retinal thickness and macular pigment optical density in a group of healthy subjects. We report that macular pigment optical density (MPOD) has a significant and positive relationship with central retinal thickness as measured by optical coherence tomography. The strength of the observed relationship (r approximately 0.30) was independent of the technique used to measure MPOD, whether heterochromatic flicker photometry (HFP) or 2-wavelength autofluorescence (AF). Of note, there was no statistically demonstrable relationship between MPOD at an eccentricity of 1- or 2-degrees and central retinal thickness. This finding has important implications for future studies investigating MPOD, and its response to dietary modification/supplementation.
Macular pigment may protect against age related macular degeneration (AMD), because of its capability to absorb blue light and scavenge free radicals. Since age is the major risk factor in AMD, a fundamental question to be answered is the possible age dependence of the macular pigment optical density (MPOD) in normal healthy subjects. In this study we used five methods to study a possible age effect: heterochromatic flickerphotometry, two setups for fundus reflectance spectroscopy, a Scanning Laser Ophthalmoscope (SLO) for obtaining reflectance, and the same SLO for autofluorescence maps. MPOD was determined from the reflected light by a full spectral analysis. We also used a new, directional analysis of the reflected light to estimate MPOD. The latter avoids the disturbing influence of stray-light. Digital subtraction at two wavelengths of log reflectance and digital subtraction of log autofluorescence obtained with the SLO provided MPOD maps. Together, all methods of measuring and of analysis provided seven MPOD estimates per subject. A total of 53 subjects, aged 19-76 years, completed all five measurements (and thus seven analyses). An additional 81 subjects, aged 18-70 years, were measured with one setup for fundus reflectance spectroscopy (and thus only two analyses). We could not find any association with age with all the objective techniques. Only MPOD values obtained with heterochromatic flickerphotometry showed a small, but significant decrease with age. This decrease was caused by an increase in the parafoveal data, suggesting that the central MPOD is unchanged with age. The bivariate correlation coefficients between all methods were significant (all p<0.001).
The human macular pigment has been found to be composed to two chromatographically separable components, which are tentatively identified as lutein [(3R,3'R,6'R)-beta,epsilon-Carotene-3,3'-diol] and zeaxanthin [(3R,3'R)-beta,beta-Carotene-3,3'-diol]. Chromatograms of retinal extracts, obtained by HPLC on three different stationary phases, were found to match those obtained with mixtures of lutein and zeaxanthin standards. Identical retention times were confirmed by coinjection of each of the isolated components with the appropriate standard. U.V.-visible spectra of the purified components were identical in all respects with those of lutein and zeaxanthin. Further support for our identification was obtained by the preparation and chromatographic comparison of derivatives of the macular pigment and of the standards.
PURPOSE: Research shows wide variation in macular pigment density between individuals. As are other ocular pigments, this variation may be genetic. To test this hypothesis, the authors measured macular pigment density, serum carotenoid concentrations, and general dietary patterns in 10 pairs of identical twins. METHODS: Macular pigment was measured psychophysically by a 1 degree test stimulus. Foveal and parafoveal sensitivities to 460-nm and 530-nm light were compared. Determining the difference in log sensitivity to the 460-nm light for the fovea (where macular pigment is most dense) and the parafovea (where macular pigment is optically immeasurable), after normalizing with respect to 530 nm, yields a measurement of the optical density of macular pigment. Concentrations of carotenoids within the serum were measured using reverse-phase, high-performance liquid chromatography. Dietary patterns were determined using a food-frequency questionnaire. RESULTS: Statistically significant differences in macular pigment optical density were found for 5 of the 10 twin pairs. For these five pairs, differences in macular pigment density were moderately related to differences in the intake of dietary fat, iron, linoleic and oleic acid, fiber, and total calories (P < 0.10, individually; P < 0.05, for an equally weighted composite of these variables). There was no significant relationship, however, found between macular pigment density and carotenoids in the blood and diet. CONCLUSIONS: Given the putative protective role of macular pigment, variations in macular pigment density may have clinical significance. The conclusion that macular pigment is not completely determined genetically allows the possibility that macular pigment density may be modified for the protective purposes. The current data suggest that dietary fat, iron, and fiber may influence macular pigment levels (perhaps through their influence on carotenoid metabolism). These data suggest that the eventual deposition of macular pigment in the retina is complex and probably is influenced by a number of variables.
PURPOSE: To determine the influence of macular pigment absorption on blue-on-yellow perimetry using a technique suitable for application with the Humphrey Field Analyzer. METHODS: The sample comprised one eye from each of 46 healthy subjects (age range, 20-80 years). Macular pigment absorption was assessed by measuring medium-wavelength sensitive cone sensitivity for 460- and 570-nm narrowband stimuli at the fovea, at 5.5 degrees and at 8 degrees eccentricity. The differences in sensitivities recorded between the fovea and 8 degrees eccentricity and between 5.5 degrees and 8 degrees eccentricity for the 460-nm stimulus relative to a value of zero at 570 nm were attributed to absorption by the macular pigment. Blue-on-yellow perimetry was undertaken using a 460-nm narrowband blue Goldmann size V stimulus and a yellow 330-cdm-2 background. RESULTS: Group macular pigment absorption (mean +/- standard error) was 0.40 +/- 0.03 log units foveally and 0.00 +/- 0.03 log units at 5.5 degrees eccentricity. The group mean foveal macular pigment absorption was significantly different from zero (P < 0.01). The coefficient of repeatability for the macular pigment absorption procedure (based on test-retest data for 16 subjects) was +/- 0.28 log units at the fovea and +/- 0.35 log units at 5.5 degrees eccentricity. CONCLUSION: The net effect of ocular media and macular pigment absorption relative to 460 nm was to attenuate the blue-on-yellow visual field at the fovea by approximately 0.80 log units and elsewhere by 0.40 log units.
The nonbleaching yellow pigments of the primate fovea were studied by microspectrophotometry (MSP). Retinas fixed with glutaraldehyde/paraformaldehyde mixtures retained yellow pigments with absorbance spectra very similar to those recorded by MSP in fresh retinas. This allowed the authors to prepare retinal sections for localization of the pigments. The spectrum of the macular pigment in fixed tissue is shifted slightly (about 6 nm) toward longer wavelengths, with maximum absorbance at 460 nm. Two short-wavelength yellow pigments also have been identified, with absorbance maxima at 410 nm ( P410 ) and 435 nm ( P435 ), respectively. All three yellow pigments are present in the fovea. The short-wavelength pigments are detected more easily outside the central foveal region because the macular pigment does not obscure them there. They are especially apparent when the MSP beam is confined to the outer nuclear layer or the inner segment layer of retinal sections. The macular pigment is most dense in the fiber layers (receptor axon layer and inner plexiform layer); its density declines markedly with retinal eccentricity. The maximal absorbance of P410 and P435 is usually lower than that of the macular pigment in the central fovea, but their densities and relative proportions change more gradually with eccentricity. Consequently, their maximal absorbance is higher than that of the macular pigment outside the foveal center. The P410 and P435 pigments may be two different oxidation states of one or more respiratory hemoproteins. Commonly used procedures for estimating the absorbance spectrum of the macular pigment by comparing the foveal center with a parafoveal region may be influenced by the amounts and the oxidation states of the short-wavelength pigments in the living eye.
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 degree, 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.
PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.
The predominant carotenoids of the macular pigment are lutein, zeaxanthin, and meso-zeaxanthin. The regular distribution pattern of these carotenoids within the human macula indicates that their deposition is actively controlled in this tissue. The chemical, structural, and optical characteristics of these carotenoids are described. Evidence for the presence of minor carotenoids in the retina is cited. Studies of the dietary intake and serum levels of the xanthophylls are discussed. Increased macular carotenoid levels result from supplementation of humans with lutein and zeaxanthin. A functional role for the macular pigment in protection against light-induced retinal damage and age-related macular degeneration is discussed. Prospects for future research in the study of macular pigment require new initiatives that will probe more accurately into the localization of these carotenoids in the retina, identify possible transport proteins and mechanisms, and prove the veracity of the photoprotection hypothesis for the macular pigments.
PURPOSE: To measure the optical density of the crystalline lens and macular pigments in a group of patients with diabetes mellitus and compare the results with those in a group of control subjects. METHODS: Color matches were performed using a Wright tristimulus colorimeter. The reference wavelength used was 490 nm, desaturated with 650 nm. Lens optical density was measured by mixing spectral primaries of wavelengths 420, 515, and 650 nm to match the reference. Wavelengths 420 and 515 nm were chosen, because they are absorbed equally by the macular pigment. To measure macular pigment density, two color matches were performed, one foveal and one 5 degrees extrafoveal. The reference stimulus was matched by mixing spectral primaries of 460, 530, and 650 nm. The ratio of the foveal to extrafoveal color match gives the optical density of the macular pigment. Thirty-four diabetic patients and 34 control subjects performed the lens density color match, and of these, 26 diabetic patients and 30 control subjects performed the macular pigment density color matches. RESULTS: There is a significant increase in the optical density of the lens in diabetes with age in comparison to the control subjects (P < 0.001), with a duration dependence of 0.02 log units/year. The mean macular pigment density in the diabetic patients was 0.13 +/- 0.20 log units and in the control subjects 0.32 +/- 0.24 log units (P = 0.0015). Patients with grade 2 maculopathy had significantly lower pigment density than those with no maculopathy (P = 0.016). CONCLUSIONS: The ocular media of diabetic persons are abnormal, with increased lens and reduced macular pigment optical density. The relationship between reduced macular pigment levels with increasing severity of maculopathy may implicate oxidative stress as a causative factor.
Interocular differences in the optical density of macular pigment were examined. Foveal and parafoveal sensitivities to lights of 460 and 530 nm were measured by heterochromatic flicker photometry for both eyes of ten subjects. These two wavelengths represent the maximum and minimum absorbance for macular pigment. Taking the difference in log sensitivity to the 460 nm light for the fovea and parafovea, after normalizing with respect to 530 nm, yields a measurement of the optical density of the macular pigment. Consistent interocular differences in macular pigment density were found for only two subjects, and these differences were less than 0.1. Other subjects frequently showed significant interocular differences on a given day but showed no consistent differences over the course of many days. In general, the amount of macular pigment measured for one eye was found to be essentially the same as that for the other eye. When measurements were averaged for the two eyes of each subject, significant differences in macular pigment density among subjects were found.
BACKGROUND: It has been reported that the differences in macular pigment between Asian and Caucasian eyes might give rise to different performance on the Farnsworth-Munsell 100 Hue test. However, the study did not appear to account adequately for the observation that differences were apparent only in older age groups. It was also acknowledged that other factors, like pupil size and crystalline lens colouration, could influence the result. METHOD: We investigated the performance of the Farnsworth-Munsell 100 Hue test, under standard conditions, by three groups with presumed different macular pigmentation and narrow age range. We also measured pupil size. RESULTS: The group with blue irides (presumed low macular pigmentation) performed significantly better on the colour vision task than the Asian group and the brown-eyed subjects as a whole (presumed higher macular pigmentation). In addition, the difference in pupil size between the blue-eyed group and brown-eyed groups bordered on significance. The difference in pupil size and consequential reduction in retinal illuminance account for a significant proportion of the difference in colour vision performance. In addition, a difference in both pupil size and Farnsworth-Munsell 100 Hue test performance was also observed between males and females that reinforced the importance of pupil size, and not just macular pigment, as a factor in colour vision performance difference between Asian and non-Asian eyes. CONCLUSION: It is concluded that pupil size, not just macular pigment, may have a significant influence on colour vision performance in a young, healthy population.