HPLC measurement of ocular carotenoid levels in human donor eyes in the lutein supplementation era

PURPOSE: A substantial proportion of the population at risk for visual loss from age-related macular degeneration consumes supplements containing high doses of lutein, but clinical studies to date have shown only modest and variable increases in macular carotenoid pigments in response to supplementation. To determine whether lutein supplementation can indeed alter ocular carotenoid levels, the authors chemically measured levels of lutein, zeaxanthin, and their metabolites in the macula, peripheral retina, and lens of 228 eyes from 147 human donors and correlated these results with retrospective supplement histories from families of selected members of the study population. METHODS: Lenses and circular punches of macula (4-mm diameter) and equatorial peripheral retina (8-mm diameter) were dissected from donor eyes free of ocular disease procured from the local eye bank. The amounts of lutein, zeaxanthin, meso-zeaxanthin, and 3'-oxolutein were determined by HPLC with photodiode array and mass spectral detection. RESULTS: Eighteen percent of eyes from donors age 48 and older had unusually high levels (66.3 +/- 15.1 ng) of macular carotenoids that were three times the rest of the older population's mean level (23.0 + 12.1 ng; P < 0.001). Carotenoid levels in these outliers were also unusually high in the lens and in the peripheral retina. Similar outliers were not present in donors younger than 48. Most of these outliers regularly consumed high-dose lutein supplements before death. Lutein supplementation was uncommon in older donors whose macular carotenoids were in the normal range. CONCLUSIONS: The presence of unusually high levels of macular carotenoids in older donors who were regularly consuming high-dose lutein supplements supports the hypothesis that long-term lutein supplementation can raise levels of macular pigment. Elevated carotenoid levels in the peripheral retina and lens in these same donors could have important implications for understanding why some clinical methods of macular pigment measurement have had difficulty detecting robust and consistent responses in carotenoid supplementation trials.     

Macular Pigment Imaging in AREDS2 Participants: An Ancillary Study of AREDS2 Subjects Enrolled at the Moran Eye Center

Purpose. Age-Related Eye Disease Study 2 (AREDS2) is a randomized, placebo-controlled study designed to determine whether supplementation with 10 mg of lutein and 2 mg of zeaxanthin per day can slow the rate of progression of age-related macular degeneration (AMD). Although some biomarkers of response to carotenoid supplementation such as serum concentrations are part of the AREDS2 protocol, measurement of carotenoid concentrations in the eye and other tissues is not. In this approved ancillary study, macular pigment optical density (MPOD), macular pigment distributions, and skin carotenoid levels at enrollment and at each annual visit were measured to assess baseline carotenoid status and to monitor response to assigned interventions. Methods. All subjects enrolled at the Moran Eye Center had MPOD and macular pigment spatial distributions measured by dual-wavelength autofluorescence imaging and total skin carotenoids measured by resonance Raman spectroscopy. Results. Baseline MPOD in enrolled subjects was unusually high relative to an age-matched control group that did not consume carotenoid supplements regularly, consistent with the high rate of habitual lutein and zeaxanthin consumption in Utah AREDS2 subjects prior to enrollment. MPOD did not correlate with serum or skin carotenoid measurements. Conclusions. Useful information is provided through this ancillary study on the ocular carotenoid status of AREDS2 participants in the target tissue of lutein and zeaxanthin supplementation: The macula. When treatment assignments are unmasked at the conclusion of the study, unique tissue-based insights will be provided on the progression of AMD in response to long-term, high-dose carotenoid supplementation versus diet alone. (ClinicalTrials.gov number, NCT00345176.).     

Light exposure and macular pigment optical density

PURPOSE: Biochemical research has demonstrated that lutein and zeaxanthin, the two macular carotenoids, are bleachable pigments. Further, evidence suggests that exposure to UV light can degrade plasma carotenoid levels in vivo. The present study investigated the effects of exposure to normal levels of light on the levels of lutein and zeaxanthin in the retina. METHODS: The optical density of macular pigment (MPOD) was measured in two male subjects under four different light-adaptation conditions for 20 days. Heterochromatic flicker photometry was used to measure MPOD at 0.5 degrees eccentricity. RESULTS: The four conditions of light adaptation did not significantly affect MPOD. As in previous studies, however, a significant day-to-day difference was observed for both subjects. CONCLUSIONS: The results suggest that lutein and zeaxanthin levels in the eye are unaffected by light and oxidation throughout the day. This justifies current research methods in which MPOD measures are made regardless of the time of day. However, significant between-day variance indicates that multiple MPOD measures may be necessary to evaluate lutein and zeaxanthin levels in the retina accurately.     

Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population

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.     

Macular pigment: new clinical methods of detection and the role of carotenoids in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in people over the age of 65. The Age-Related Eye Disease Study (AREDS) suggests antioxidants may delay the advance of age-related macular degeneration. The macular pigments zeaxanthin and lutein may serve as antioxidants as well as blue filter to protect the retina. In this review, the general characteristics of macular pigment are described. The nutritional value of zeaxanthin/lutein and methods to assess macular pigment are discussed. Several emerging instruments to assess macular pigment, including heterochromatic flickering photometer, motion detection photometer, fundus reflectance spectroscope, Raman spectrometer, and autofluorescence spectrometry, are introduced and reviewed. Optometrists should be aware that they may play a role to assess and monitor the risk of AMD. There is an opportunity to incorporate measurement of macular pigment in optometric practice.     

Decreased arterial dye-filling and venous dilation in the macular choroid associated with age-related macular degeneration

PURPOSE: To compare the angioarchitecture of choroidal arteries and veins in patients with age-related macular degeneration (AMD) to the angioarchitecture of age-matched normal subjects using indocyanine green (ICG) angiography. METHODS: ICG angiography was performed in 35 consecutive AMD patients and 18 normal age-matched volunteers with a fundus ICG camera. ICG video images, including the arterial and venous phases, were quantitatively analyzed using image analyzing software. RESULTS: In patients with AMD, the choroidal arterioles are dilated, fewer, run a straighter course, and possess fewer bifurcations. The number of choroidal arteries and the macular fluorescent intensity in the arterial phase of choroidal filling was significantly less in patients with AMD as compared to age-matched normal controls (P = 0.008). The mean and maximum caliber of choroidal veins in the macula was dilated in AMD eyes than in age-matched normal control eyes (P < 0.001). There was no statistically significant difference in arterial dye filling or venous caliber observed in AMD eyes, with or without choroidal neovascular membrane (CNV). CONCLUSION: Choroidal arterial perfusion in the macula was significant decreased in eyes with AMD with and without CNV, and was associated with choroidal venous dilation. These observations implicate poor choroidal perfusion of the macula in the pathogenesis of AMD.     

Relationship between macular pigment and visual acuity in eyes with early age‐related macular degeneration

Purpose: Today the extent to which MP impacts visual function in early AMD remains unclear. This study examines the relationship between macular pigment optical density (MPOD) and high‐contrast visual acuity (HC‐VA) and low‐contrast visual acuity (LC‐VA) in eyes with early age‐related macular degeneration (AMD). Methods: Measurements were made in 22 subjects with early AMD and 27 healthy control subjects. Distance best‐corrected VA was measured using HC (96%) and LC (10%) Bailey‐Lovie logMAR letter charts under photopic luminance conditions. MPOD was determined at the fovea through apparent motion photometry using the cathode ray tube‐based Metropsis psychophysical vision test (Cambridge Research Systems). Results: No significant differences in foveal MPOD were detected between the control eyes (0.30 ± 0.24 log units) and eyes with early AMD (0.27 ± 0.15 log units). Neither were differences detected between the two groups in mean HC‐ and LC‐VA. Foveal MPOD showed significant correlation with both photopic HC‐VA (r = ?0.47, p = 0.0008) and LC‐VA (r = ?0.46, p = 0.0008) such that as MPOD increased, photopic HC‐VA and LC‐VA improved (lower logMAR values). Conclusions: Low MP levels were related to worse visual function in both healthy eyes and eyes with early AMD. Our findings provide direction for future studies designed to improve retinal function through the use of oral supplements known to increase MP levels, especially in eyes with AMD and a low MPOD.     

The macular xanthophylls

The macular pigments are predominantly composed of three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. These carotenoids are concentrated and distributed in a selective manner. The properties of these pigments are further explored along with their methods of uptake, stabilization, and storage. The dual nature of these pigments as filters and antioxidants are elaborated upon in relation to their protective effects upon the macula, specifically in age-related macular degeneration. Evidence suggests that increased levels of macular pigment are correlated with a decreased risk of age-related macular degeneration. Many have sought to exploit this therapeutic relation. Studies reveal that oral supplementation with lutein and zeaxanthin can increase the levels of macular pigments in the retina and plasma. The effects of such supplementation on actual ocular function have yet to be fully addressed. New and standardized methods of assessing macular pigment density are discussed and future areas of research to further our understanding of macular xanthophylls as they pertain to age-related macular degeneration are highlighted.     

The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older

PURPOSE: To investigate the effect of lutein supplementation at doses of 2.5, 5.0, and 10 mg/d for 6 months on distribution of these carotenoids and their metabolites in the serum of elderly human subjects, with and without age-related macular degeneration. To determine whether supplementation with lutein can interact with the serum levels of other dietary carotenoids, retinol, and alpha-tocopherol. METHODS: Forty-five subjects received daily supplements of lutein (containing 5% zeaxanthin) for 6 months and were followed up for another 6 months after supplementation. Blood was collected at various intervals and lutein, zeaxanthin, and their metabolites in the sera were quantified by normal-phase high-performance liquid chromatography (HPLC)-UV/visible detection. Other dietary carotenoids, retinol, and alpha-tocopherol were identified and quantified on a C18 reversed phase HPLC column. RESULTS: After 6 months of supplementation with 10 mg of lutein, the increases in the mean serum levels from baseline were: 210 to 1000 nM/L (P < 0.0001) for lutein and 56 to 95 nM/L (P < 0.0001) for zeaxanthin. Similarly, the mean concentrations (nM/L) of carotenoid metabolites increased from 49 to 98 (P < 0.0001) for 3-hydroxy-beta,epsilon-caroten-3'-one (3'-oxolutein); 31 to 80 (P < 0.0001) for 3'-hydroxy-epsilon,epsilon-caroten-3-one; and 19 to 25 (P < 0.0001) for epsilon,epsilon-carotene-3,3'-dione. The serum levels of these carotenoids gradually decline within 6 months after supplementation. CONCLUSIONS: The increase in the serum levels of lutein/zeaxanthin correlates with increases in the serum levels of their metabolites that have previously been identified in the ocular tissues. Elderly human subjects with and without AMD can safely take supplements of lutein up to 10 mg/d for 6 months with no apparent toxicity or side effects.     

The value of measurement of macular carotenoid pigment optical densities and distributions in age-related macular degeneration and other retinal disorders

There is increasing recognition that the optical and antioxidant properties of the xanthophyll carotenoids lutein and zeaxanthin play an important role in maintaining the health and function of the human macula. In this review article, we assess the value of non-invasive quantification of macular pigment levels and distributions to identify individuals potentially at risk for visual disability or catastrophic vision loss from age-related macular degeneration, and we consider the strengths and weaknesses of the diverse measurement methods currently available.     

Macular pigment density and aging, assessed in the normal elderly and those with cataracts and age-related macular degeneration

PURPOSE: Increasing evidence has linked retinal lutein and zeaxanthin (termed macular pigment, MP) to the risk of age-related macular degeneration (AMD). Currently, however, studies differ regarding the question of whether MP declines with age or age has an effect in patient populations being assessed. This study assessed MP across the lifespan with an emphasis on assessing MP in a cross-section of elderly including those with lenticular or age-related macular degeneration, or both. DESIGN: Prospective, observational, cross-sectional study. METHODS: SETTING: Institution. STUDY POPULATION: Cross-sectional study of normal, cataractous, and AMD subjects tested in Indianapolis, Indiana, including 390 subjects, 22 with cataracts and 59 with age-related macular degeneration. OBSERVATIONAL PROCEDURE: MP density was measured with a one-degree diameter test field at 460 nm using a psychophysical method based on heterochromatic flicker photometry. MAIN OUTCOME MEASURES: MP optical density. RESULTS: MP does not appear to change as a function of age (r = +.04) when examining subjects across the lifespan (from 18-88 years). There was a slight tendency (slope = -.0027, r = -.11) for MP to decline when only the elderly subjects were considered, but this trend was not significant (P < .12) for any of the groups considered (normal, cataractous, or AMD). CONCLUSIONS: MP does not change significantly with age, even when elderly subjects with cataracts and AMD are considered. Using heterochromic flicker photometry, elderly subjects display a full range of MP density that is similar to young subjects.     

Macular pigment levels following successful macular hole surgery

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.     

The utility of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment in patients with age-related macular degeneration

The purpose of this study was to assess the utility and validity of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment optical density (MPOD) in patients with intermediate stages of age-related macular degeneration (AMD). The measurement procedure was optimized to accommodate individual differences in temporal vision related to age, disease, or other factors. The validity criteria were based on the similarity of the spectral absorption curves to ex vivo curves of lutein and zeaxanthin and the similarity of spatial density profiles to those measured in subjects without retinal disease. Macular pigment optical density (MPOD) spatial profiles were measured with an LED-based macular densitometer; spectral absorption curves were measured with a 3-channel Maxwellian view system including a monochromator. All patients were characterized via clinical exams and all but 2 subjects from whom data were obtained had masked grading of color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. Most of the patients were in AREDS category 2 (27%) or 3 (57%). Patients with visual acuity as poor as 20/80 were included, and could perform the task as long as they could see the stimulus. Eighty-one percent of the patients screened were able to perform the cHFP task, and data were obtained from 30 AMD patients. Spatial profiles of MPOD were measured in 19 subjects who could see the stimulus at all tested loci. These profiles were highly similar to those that have been measured with HFP in subjects without retinal disease. The average shape of the spectral absorption curves for the AMD subjects corresponded well to an ex vivo template. These data support both the utility and validity of the cHFP method for measuring MPOD in subjects with intermediate stages of AMD. The ability to measure the retinal response to nutritional intervention is of practical importance for monitoring patients being supplemented with lutein and zeaxanthin in hopes of retarding visual loss and/or disease progression.     

TIMP-3 in Bruch's membrane: changes during aging and in age-related macular degeneration.

PURPOSE: To assess the distribution, content, and function of tissue inhibitor of metalloproteinases (TIMP)-3 during aging in normal eyes for comparison with the levels observed in eyes with age-related macular degeneration (AMD). METHODS: Donor tissues analyzed included 36 normal eyes (14-96 years old) and 15 AMD eyes (74 -98 years old). A tissue strip including the fovea was used for immunohistochemistry. Western blot analysis was performed on extracts of the retinal pigment epithelium (RPE)- choroid complex from the posterior part of each eye. Immunoreactivity of TIMP-3 bands in each western blot was densitometrically quantitated. The inhibitory function of TIMP-3 was evaluated with reverse zymography. RESULTS: TIMP-3 was present uniformly across Bruch's membrane in the normal samples. In samples from donors more than 50 years of age, immunostaining was intense. TIMP-3 content ranged from 92 to 1061 ng/cm2 and increased with age (r = 0.66). In AMD eyes, TIMP-3 distribution in Bruch's membrane was abundant in areas of continuous soft drusen but absent in areas below RPE atrophy. TIMP-3 levels in AMD eyes were significantly higher than in age-matched normal eyes (577 versus 877 ng/cm2; P = 0.009). Inhibitory activity correlated well with TIMP-3 content (r = 0.82) and was also significantly higher in AMD eyes than in age-matched normal eyes (P < 0.001). CONCLUSIONS: During normal aging, TIMP-3 content in Bruch's membrane of the macula shows a significant increase. TIMP-3 content in AMD eyes was elevated relative to that of age-matched normal eyes. Higher levels of TIMP-3 may contribute to the thickening of Bruch's membrane observed in AMD.     

Macular function in eyes with early age-related macular degeneration with or without contralateral late age-related macular degeneration

PURPOSE: To evaluate psychophysical and electrophysiologic responses in eyes with early age-related macular degeneration (AMD) without a decrease in visual acuity and with or without late AMD in the fellow eye. METHODS: Fifteen patients (mean age: 67.9 +/- 7.20 years) with early AMD in both eyes (AMD1 group, 15 eyes) and 15 patients (mean age: 71.40 +/- 7.06 years) with early AMD in one eye and late AMD in the fellow eye (AMD2 group, 15 eyes) were enrolled. They were compared to 15 age-similar normal control subjects. LogMAR visual acuity (VA), macular sensitivity by MP-1 microperimetry, and multifocal electroretinograms (mfERG) were assessed in control, AMD1, and AMD2 eyes. mfERG response amplitude density (RAD, nV/deg2) of the N1-P1 component of first order binary kernels was measured. RESULTS: When compared to controls, AMD1 and AMD2 eyes showed a significant (analysis of variance, P < 0.01) decrease in MP-1 microperimetry assessed in the 0-2.5 and 2.5-5 degrees of the macula, significantly correlated (Pearson test, P < 0.01) to the corresponding significant decrease (P < 0.01) in mfERG N1-P1 RADs assessed in the 0-2.5 and 2.5-5 degrees. In AMD1 and AMD2 eyes, VA and mfERG N1-P1 RADs assessed in the 5-20 degrees were similar (P > 0.01) to controls. VA, MP-1, and mfERG values were not significantly different in AMD1 and AMD2 eyes. CONCLUSION: In eyes with early AMD there is a dysfunction of preganglionic elements in the central 0-5 retinal degrees detectable by mfERG or MP-1 microperimetry. This impairment is not further influenced by the presence of late AMD in the fellow eye.     

Dose-ranging study of lutein supplementation in persons aged 60 years or older

PURPOSE: To examine the dose-response relationship between oral lutein supplementation and serum lutein concentrations in persons aged 60 years and older, with or without age-related macular degeneration (AMD). METHODS: Forty-five participants with no AMD, large drusen, or advanced AMD, were randomized to receive one of three doses (2.5, 5, or 10 mg) of lutein for 6 months and to be observed for 6 additional months after the cessation of lutein supplementation. RESULTS: The mean age of the participants (33 women) was 71 years (range: 60-91). The serum lutein concentrations of each dose group were similar before supplementation, increased at 1 month, and peaked by 3 months. Median serum concentrations of the 2.5-, 5-, and 10-mg groups from baseline to month 6 increased from 18.7 to 35.1 microg/dL (2-fold increase), from 17.8 to 59.2 microg/dL (2.9-fold increase), and from 15.1 to 66.8 microg/dL (4-fold increase), respectively (all P < 0.001). The increases in lutein serum concentrations did not vary with AMD disease severity (P = 0.98). No toxicity was observed with any dose of lutein. No significant changes were detected in visual acuity or visual field tests. CONCLUSIONS: Increasing doses of lutein supplements significantly increased the serum levels of lutein and zeaxanthin, and doses up to 10 mg were safely administered. A long-term large clinical trial is necessary to investigate the safety and efficacy of lutein in reducing the risk of the development of advanced AMD.     

Lutein and antioxidants in the prevention of age-related macular degeneration

Demographic developments in Europe and North America are causing an increase of age-related diseases. Age-related macular degeneration (AMD) is one of the leading causes of severe central visual acuity loss in elderly people and seems to be an economic problem, too. There is evidence that oxidative damage is an important factor for exacerbation of AMD. Macular pigment with its antioxidative effect may serve as"natural sunglasses" filtering the blue light acting as a possible source of photooxidative damage to the neurosensory retina. The macular pigment consists mostly of lutein and zeaxanthin. These micronutrients from the group of carotenoids, as is the case for vitamins (vitamins C, E, and beta-carotene), cannot be synthesized in mammals and that is the reason why the role of micronutrition or its supplementation and its correlation to AMD progression has been discussed for years.The results of currently published studies are often contradictory. At present there are no results from randomized controlled studies confirming that supplementation of lutein and zeaxanthin can reduce the risk for AMD. Several epidemiological studies investigating the impact of antioxidants and omega-3 fatty acids on the incidence of AMD provided conflicting results.Up to now, AREDS is the largest randomized controlled study investigating the effect of supplementation of antioxidants, zinc, and copper on the progression of AMD. AREDS showed a significant effect of this supplementation in some particular groups of patients with AMD. The supplementation of lutein and omega-3 fatty acids is not toxic but a positive effect has not been proven by randomized studies.     

The role of oxidative stress in the pathogenesis of age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of blind registration in the developed world, and yet its pathogenesis remains poorly understood. Oxidative stress, which refers to cellular damage caused by reactive oxygen intermediates (ROI), has been implicated in many disease processes, especially age-related disorders. ROIs include free radicals, hydrogen peroxide, and singlet oxygen, and they are often the byproducts of oxygen metabolism. The retina is particularly susceptible to oxidative stress because of its high consumption of oxygen, its high proportion of polyunsaturated fatty acids, and its exposure to visible light. In vitro studies have consistently shown that photochemical retinal injury is attributable to oxidative stress and that the antioxidant vitamins A, C, and E protect against this type of injury. Furthermore, there is strong evidence suggesting that lipofuscin is derived, at least in part, from oxidatively damaged photoreceptor outer segments and that it is itself a photoreactive substance. However, the relationships between dietary and serum levels of the antioxidant vitamins and age-related macular disease are less clear, although a protective effect of high plasma concentrations of alpha-tocopherol has been convincingly demonstrated. Macular pigment is also believed to limit retinal oxidative damage by absorbing incoming blue light and/or quenching ROIs. Many putative risk-factors for AMD have been linked to a lack of macular pigment, including female gender, lens density, tobacco use, light iris color, and reduced visual sensitivity. Moreover, the Eye Disease Case-Control Study found that high plasma levels of lutein and zeaxanthin were associated with reduced risk of neovascular AMD. The concept that AMD can be attributed to cumulative oxidative stress is enticing, but remains unproven. With a view to reducing oxidative damage, the effect of nutritional antioxidant supplements on the onset and natural course of age-related macular disease is currently being evaluated.     

Macular pigment and percentage of body fat

PURPOSE: To investigate the relationship between percentage of body fat and macular pigment (MP) optical density. METHODS: One hundred healthy subjects of ages between 22 and 60 years volunteered to participate in this study. MP optical density was measured psychophysically, serum lutein and zeaxanthin were quantified by HPLC, and dietary intake of lutein and zeaxanthin was assessed using a validated food frequency questionnaire. Body fat was measured by dual energy x-ray absorptiometry (DEXA); body mass index (BMI) was also calculated for each subject. Clinical and personal details were recorded, with particular attention directed toward putative risk factors for AMD. RESULTS: There was a significant inverse relationship between the percentage of body fat and MP optical density in males (r=-0.392, P <0.01), and after correcting for age and dietary lutein and zeaxanthin, this inverse relationship remained significant (r=-0.290, P <0.05). The relationship between MP optical density and percentage of body fat in females was inverse, but not significant (r=-0.197, P=0.149). A significant and inverse relationship between serum zeaxanthin and percentage of body fat was observed for females only (r=-0.354, P <0.01). Dietary intake of fat was inversely related to serum lutein and zeaxanthin, and significantly so for lutein (r=-0.256, P <0.05). However, dietary fat was unrelated to MP optical density (r=0.041, P=0.688). CONCLUSIONS: A relative lack of MP is associated with adiposity in men, and may underlie the association between body fat and risk for AMD progression in males. Further, the processes governing accumulation and/or stabilization of lutein and zeaxanthin in fat tissue appear to differ for males and females.     

Autologous translocation of the choroid and retinal pigment epithelium in age-related macular degeneration

PURPOSE: To evaluate the autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in 45 eyes of 43 patients with age-related macular degeneration (AMD). DESIGN: Prospective nonrandomized study. METHODS: All patients had visual loss due to AMD (n = 5 classic membranes, n = 14 occult, n = 2 mixed, n = 16 pigment epithelial detachment (PED), n = 5 subretinal hemorrhage, n = 3 geographic atrophy). After extraction of the neovascular complex, an autologous peripheral full-thickness explant of RPE, Bruch membrane, and choroid was translocated from the midperiphery to the macula. RESULTS: Preoperative distant visual acuity ranged from 20/800 to 20/40. Reading vision ranged from 1.4 logarithm of reading acuity determination (logRAD) to 0.5 logRAD (0.04 to 0.32 Snellen equivalent). Revision surgery was required in 22 eyes as a result of proliferative vitreoretinopathy (PVR), retinal detachment, macular pucker, or vitreous hemorrhage. In eight patients, the patch was renewed. At six months, distant visual acuity ranged from light perception to 20/50 (increase of 15 letters in four eyes). Reading vision ranged from 1.4 to 0.4 logRAD. Visual outcome was unrelated to the type of AMD. Vascularization of the transplant was visible on indocyanine green (ICG) angiography in 40 of 42 eyes. In most patients, autofluorescence of the pigment epithelium was coincident with revascularization of the graft. Fixation on the patch was positively related to visual acuity. CONCLUSIONS: Autologous translocation of a full-thickness transplant of choroid and RPE usually results in a vascularized and functioning graft. Vascularization was even achieved in patients with geographic atrophy. Fixation stability and microperimetry before the patch translocation may be helpful in selecting patients who will profit from surgery.