Early retinal vascular abnormalities in African-American cocaine users.

PURPOSE: To investigate whether cocaine use is associated with early retinal vascular abnormalities. DESIGN: Population-based cross-sectional study. SETTINGS: Inner-city neighborhoods in Baltimore, Maryland. STUDY POPULATION: Sixty-eight participants were recruited from an ongoing observational study, investigating cardiovascular complications of human immunodeficiency virus (HIV) infection and cocaine use in African Americans aged between 25 and 54 years. Those with hypertension and known cardiovascular/cerebrovascular diseases were excluded. OBSERVATION PROCEDURES: Ophthalmoscopic examinations and fundus photography of the retinas of these subjects were performed after pupillary dilation. The largest angle of arterial bifurcation (LAAB), central retinal artery equivalent (CRAE), and central retinal vein equivalent (CRVE) were measured by single-masked fundus image examiners. MAIN OUTCOME MEASURES: LAAB, CRAE, and CRVE. RESULTS: Among the 68 study subjects, 52 (76.5%) were chronic cocaine users and 16 (23.5%) were non-cocaine users. Univariate and multivariate analyses indicated that the LAAB was associated with age and duration of cocaine use of more than 10 years. The LAAB was also inversely associated with very low-density lipoproteins levels. Multivariate analysis indicated a positive association between CRVE and cocaine use. CRAE was also associated with intravenous injection. We confirmed that CRAE was inversely associated with age. HIV infection was not found to be associated with any retinal vascular parameters. CONCLUSIONS: Cocaine use is associated with increased retinal arterial branching angle and venular caliber. The retinal vascular changes provided the first evidence that cocaine use has an effect on the retinal vascular system.

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.

Nutritional manipulation of primate retinas. IV. Effects of n--3 fatty acids, lutein, and zeaxanthin on S-cones and rods in the foveal region.

Lutein and zeaxanthin are xanthophylls selectively accumulated by primate retinas that may protect the macula from age-related macular degeneration. In this project, we manipulated n-3 fatty acids, lutein and/or zeaxanthin levels in the diet and studied their possible outcome on S-cone and rod cell density in the foveal region. Rhesus monkeys (7-16 year, n=17) were fed from birth xanthophyll-free semipurified diets with either adequate or low n-3 fatty acids. Five monkeys were supplemented with lutein and six with zeaxanthin for 6-24 months, while six remained xanthophyll-free until sacrifice. Retinas were embedded in methacrylate and serial 2 microm sections were cut along the vertical meridian. Rod nuclei, and immuno-labelled outer segments of S-cones and rods, were reconstructed and counted in an 8 microm strip. The density profiles were compared with data from control monkeys (n=7) fed a standard laboratory diet. S-cone density profiles were symmetrical along the vertical meridian and the densities decreased rapidly with retinal eccentricity. Rod densities were higher in the superior region than the inferior region in most of the control and experimental animals. Unlike the significant effects observed for retinal pigment epithelial cells of these same monkeys (Leung, I.Y-F., Sandstrom, M.M., Zucker, C.L., Neuringer, M., Snodderly, D.M., 2004. Nutritional manipulation of primate retinas. II. Effects of age, n-3 fatty acids, lutein, and zeaxanthin on retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 45, 3244-3256), neither xanthophyll supplementation nor low dietary n-3 fatty acids produced consistent effects on S-cone or rod density profiles of the experimental animals. However, monkeys low in n-3 fatty acids had increased variability of S-cone density in the fovea and low density of foveal rod outer segments. The high variability suggests that the photoreceptors of some animals were resistant to the nutritional manipulations, while others may have been affected. Thus, the photoreceptors appear less sensitive than the retinal pigment epithelium to these nutritional manipulations. However, it is possible that more consistent effects would emerge at a later age or after exposure to stressors such as high light levels.

Nutritional manipulation of primate retinas, II: effects of age, n-3 fatty acids, lutein, and zeaxanthin on retinal pigment epithelium.

PURPOSE: To study the effects of age and of n-3 fatty acids, lutein, and zeaxanthin on the retinal pigment epithelium (RPE). METHODS: Rhesus monkeys (age range, 7-17 years; n = 18) were fed xanthophyll-free semipurified diets from birth. The diets had either low or adequate amounts of n-3 fatty acids. Six monkeys remained xanthophyll-free until death. Six received supplements of pure lutein and six of pure zeaxanthin for 6 to 24 months. The central retina was serially sectioned, and the number of RPE cells were counted in an 8-microm strip along the vertical meridian. Cell counts were compared with data from control monkeys (n = 15) fed a standard laboratory diet. RESULTS: Foveal and parafoveal RPE cell densities increased with age. Xanthophyll-free monkeys had a dip in the RPE cell density profile at the foveal center, rather than the normal peak. After supplementation with xanthophylls, the RPE profile of animals low in n-3 fatty acids no longer had a dip at the foveal center but became asymmetric, with higher densities in the inferior retina. In animals with adequate n-3 fatty acid levels, xanthophyll supplementation did not restore the foveal peak, and resulted in an asymmetric profile with higher densities in the superior retina. CONCLUSIONS: RPE cells are sensitive to the absence of macular pigment. Supplemental xanthophylls interact with n-3 fatty acid levels to produce asymmetries in the RPE profile. Xanthophylls and n-3 fatty acids are essential for the development and/or maintenance of a normal distribution of RPE cells.

Retinal pigment epithelial cell distribution in central retina of rhesus monkeys.

PURPOSE: To determine the cell density profile of the retinal pigment epithelium (RPE) in the central retina and relate it to the distribution of photoreceptors. METHODS: Wholemounts of rhesus monkey (Macaca mulatta) retinas with the choroid removed but the RPE attached were stained with the nuclear stain 4',6-diamidine-2-phenylindole dihydrochloride (DAPI) and imaged with a fluorescence microscope. RPE cell nuclei were counted at the foveal center and at 0.4-mm intervals along the vertical meridian. The number of photoreceptors per RPE cell at each location was estimated by using previously published data on the distribution of rhesus photoreceptors. RESULTS: Data were collected from eight retinas. Mean RPE cell density increased from a relatively stable baseline of approximately 4000 RPE cells/mm(2) beyond 2 mm (10 degrees ) eccentricity to more than 7000 cells/mm(2) at the center of the fovea. The number of cones per RPE cell in the rhesus retina was approximately 20:1 in the foveal center (similar to the human retina) and only approximately 1.5:1 in the parafovea. However, when the rods were included, and the total number of photoreceptors per RPE cell were considered, the ratio of photoreceptors to RPE cells was lower in the fovea than in the remainder of the central retina. CONCLUSIONS: In spite of the high cone density, there is a relatively low number of photoreceptors per RPE cell in the fovea. This may limit the metabolic demands on foveal RPE cells and help to preserve their functions in the face of aging and disease.