Abstract

We present a technique for estimating the density of the human macular pigment noninvasively that takes advantage of the autofluorescence of lipofuscin, which is normally present in the human retinal pigment epithelium. By measuring the intensity of fluorescence at 710 nm, where macular pigment has essentially zero absorption, and stimulating the fluorescence with two wavelengths, one well absorbed by macular pigment and the other minimally absorbed by macular pigment, we can make accurate single-pass measurements of the macular pigment density. We used the technique to measure macular pigment density in a group of 159 subjects with normal retinal status ranging in age between 15 and 80 years. Average macular pigment density was 0.48 ± 0.16 density unit (D.U.) for a 2°-diameter test field. We show that these estimates are highly correlated with reflectometric (mean: 0.23±0.07 D.U.) and psychophysical (mean: 0.37±0.26 D.U.; obtained by heterochromatic flicker photometry) estimates of macular pigment in the same subjects, despite the fact that systematic differences in the estimated density exist between techniques. Repeat measurements over both short- and long-time intervals indicate that the autofluorescence technique is reproducible: The mean absolute difference between estimates was less than 0.05 D.U., superior to the reproducibility obtained by reflectometry and flicker photometry. To understand the systematic differences between density estimates obtained from the different methods, we analyzed the underlying assumptions of each technique. Specifically, we looked at the effect of self-screening by visual pigment, the effect of changes in optical property of the deeper retinal layers, including the role of retinal pigmented epithelium melanin, and the role of secondary fluorophores and reflectors in the anterior layers of the retina.

© 2001 Optical Society of America

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  1. S. Beatty, M. Boulton, D. Henson, H. H. Koh, I. J. Murray, “Macular pigment and age related macular degeneration,” Br. J. Ophthamol. 83, 867–877 (1999).
    [CrossRef]
  2. D. M. Snodderly, J. D. Auran, F. C. Delori, “The macular pigment. II. Spatial distribution in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 674–684 (1984).
  3. D. M. Snodderly, P. K. Brown, F. C. Delori, J. D. Auran, “The macular pigment. I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 660–673 (1984).
  4. R. A. Bone, J. T. Landrum, A. Cains, “Optical density spectra of the macular pigment in vivo and in vitro,” Vision Res. 32, 105–110 (1992).
    [CrossRef] [PubMed]
  5. G. Wyszecki, W. S. Stiles, Color Science: Concepts and Methods, Quantitative Data and Formulae, 2nd ed. (Wiley, New York, 1982).
  6. The late Dr. Paul Brown measured an absorption spectrum of MP on a fresh retinal tissue (macaqua mulata) by using microspectrophotometry (Fig. 4, central panel, in Ref. 3). The normalized absorption data are (in steps of 5 nm) 0.451 (400 nm), 0.501, 0.553, 0.605, 0.682, 0.757, 0.811, 0.844, 0.863, 0.904, 0.960, 1.000 (455 nm), 0.983, 0.923, 0.838, 0.788, 0.777, 0.763, 0.732, 0.663, 0.555 (500 nm), 0.428, 0.303, 0.196, 0.116, 0.067, 0.041, 0.026, 0.017, 0.010, and 0.005 (550 nm).
  7. G. J. Handelman, E. A. Dratz, C. C. Reay, F. J. G. M. van Kuijk, “Carotenoids in the human macula and whole retina,” Invest. Ophthalmol. Visual Sci. 29, 850–855 (1988).
  8. J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
    [CrossRef]
  9. D. M. Snodderly, “Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins,” Am. J. Clin. Nutr. 62(supplement), 1448S–1461S (1995).
    [PubMed]
  10. B. R. Hammond, E. J. Johnson, R. M. Russell, N. I. Krinsky, K. J. Yeum, R. B. Edwards, D. M. Snodderly, “Dietary modification of human macular pigment density,” Invest. Ophthalmol. Visual Sci. 38, 1795–1801 (1997).
  11. J. T. Landrum, R. A. Bone, H. Joa, M. D. Kilburn, L. L. Moore, K. E. Sprague, “One year study of the macular pigment: the effect of 140 days of a lutein supplement,” Exp. Eye Res. 65, 57–62 (1997).
    [CrossRef] [PubMed]
  12. J. S. Werner, S. K. Donnelly, R. Kliegel, “Aging and human macular pigment density,” Vision Res. 27, 257–268 (1987).
    [CrossRef]
  13. P. L. Pease, A. J. Adams, E. Nuccio, “Optical density of human macular pigment,” Vision Res. 27, 705–710 (1987).
    [CrossRef] [PubMed]
  14. B. Hammond, K. Fuld, “Interocular differences in macular pigment density,” Invest. Ophthalmol. Visual Sci. 33, 350–355 (1992).
  15. B. R. Hammond, K. Fuld, J. Curran-Celentano, “Macular pigment density in monozygotic twins,” Invest. Ophthalmol. Visual Sci. 36, 2531–2541 (1995).
  16. B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Density of the human crystalline lens is related to the macular pigment carotenoids, lutein and zeaxanthin,” Optom. Vision Sci. 74, 499–504 (1997).
    [CrossRef]
  17. B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Individual variations in the spatial profile of human macular pigment,” J. Opt. Soc. Am. A 14, 1187–1196 (1997).
    [CrossRef]
  18. D. M. Snodderly, B. R. Hammond, “In vivo psychophysical assessment of nutritional and environmental influences on human ocular tissues: lens and macular pigment,” in Nutritional and Environmental Influences on Vision, A. Taylor, ed. (CRC Press, Boca Raton, Fla., 1999), pp. 251–273.
  19. B. R. Hammond, M. Caruso-Avery, “Macular pigment optical density in a Southwestern sample,” Invest. Ophthalmol. Visual Sci. 41, 1492–1497 (2000).
  20. G. S. Brindley, E. N. Willmer, “The reflection of light from the macular and peripheral fundus oculi in man,” J. Physiol. (London) 116, 350–356 (1952).
  21. D. van Norren, L. F. Tiemeijer, “Spectral reflectance of the human eye,” Vision Res. 26, 313–320 (1986).
    [CrossRef] [PubMed]
  22. F. C. Delori, K. P. Pflibsen, “Spectral reflectance of the human ocular fundus,” Appl. Opt. 28, 1061–1077 (1989).
    [CrossRef] [PubMed]
  23. J. van de Kraats, T. T. J. M. Berendschot, D. van Norren, “The pathways of light measured in fundus reflectometry,” Vision Res. 36, 2229–2247 (1996).
    [CrossRef] [PubMed]
  24. T. Berendschot, J. van de Kraats, D. van Norren, “Three methods to measure macular pigment compared in a lutein intake study,” Invest. Ophthalmol. Visual Sci. 39, S314 (1999) [Association for Research in Vision and Ophthalmology (ARVO) Abstract No. 1665].
  25. P. E. Kilbride, K. R. Alexander, M. Fishman, G. A. Fishman, “Human macular pigment assessed by imaging fundus reflectometry,” Vision Res. 29, 663–674 (1989).
    [CrossRef] [PubMed]
  26. A. E. Elsner, S. A. Burns, E. Beausencourt, J. J. Weiter, “Foveal cone photopigment distribution: small alterations associated with macular pigment distribution,” Invest. Ophthalmol. Visual Sci. 39, 2394–2404 (1998).
  27. D. Schweitzer, M. Hammer, M. Scibor, “Imaging spectrometry in ophthalmology—principle and applications in microcirculation and in investigation of pigments,” Ophthalm. Res. 28, 37–44 (1996).
    [CrossRef]
  28. P. S. Bernstein, M. D. Yoshida, N. B. Katz, R. W. McClane, W. Gellermann, “Raman detection of macular carotenoid pigments in intact human retina,” Invest. Ophthalmol. Visual Sci. 39, 2003–2011 (1998).
  29. P. S. Bernstein, D. Y. Zhao, R. W. Ermakov, R. W. McClane, W. Gellermann, “Resonance Raman measurements of macular pigment levels in the living human retina,” Invest. Ophthalmol. Visual Sci. 40, B283 (2000) (ARVO Abstract No. 3185).
  30. F. C. Delori, “Macular pigment density measured by reflectometry and fluorophotometry,” in Opthalmic and Visual Optics and Noninvasive Assessment of the Visual System, Vol. 3 of 1993 OSA Technical Digest Series (Optical Society of America, Washington D.C., 1993), pp. 240–243.
  31. F. C. Delori, “Spectrophotometer for noninvasive measurement of intrinsic fluorescence and reflectance of the ocular fundus,” Appl. Opt. 33, 7439–7452 (1994).
    [CrossRef] [PubMed]
  32. F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).
  33. An error in DAF(460)occurs if the excitation spectrum of tissues posterior to the MP at the fovea is not proportional to that at the perifovea. We model this; we equate foveal fluorescence as FF*(Λ, λ)=kFP*(Λ, λ)+Δ(Λ, λ),where FF*and FP*are the fluorescences at the fovea and at the perifovea, respectively, k is a constant, and Δ accounts for the spectral difference between the fovea and the perifovea (can be negative). Substitution of FF*in Eq. (4) and derivation of Eq. (5), assuming that Δ/FP*≪1,gives the following approximation for the measured density: DAF′(460)≈DAF(460)+k log(e)Kmp(Λ1)-Kmp(Λ2)×Δ(Λ1, λ)FP*(Λ1, λ)-Δ(Λ2, λ)FP*(Λ2, λ).If the foveal excitation spectrum is shifted toward shorter wavelengths, then Δ decreases with increasing Λ (positive to negative), and the term in square brackets >0, resulting in an overestimation of the MP density. The opposite will occur if the shift is toward longer wavelengths.
  34. Equivalent reflectances of the fundus use a perfect Lambertian reflector located at the retina of an artificial eye as reference.21,22
  35. F. C. Delori, S. A. Burns, “Fundus reflectance and the measurement of crystalline lens density,” J. Opt. Soc. Am. A 13, 215–226 (1996).
    [CrossRef]
  36. For a subset of the population, we performed the fluorescence measurements at the peripheral site twice in the following order: excitations at 550, 510, 470, 430, 550, 510, and 470 nm. Rods were bleached only by the illumination and focusing lights before the first 550-nm exposure, whereas they were fully bleached (≈98%) by four excitation exposures before the second 550-nm exposure. For 30 subjects, the fluorescence at the second 550-nm exposure was 1.023±0.035times higher than that at the first exposure (p=0.001).This corresponds to a single-pass rod density of 0.02±0.03 D.U.at 500 nm. Thus approximately 60%–80% of the rods were bleached by the illumination and focusing lights (assuming a single-pass rod density of 0.05–0.1 D.U. at 500 nm).
  37. The distribution of retinal irradiance and sensitivity of the fluorometer in the 2° test field was measured optically by displacing a small reflecting surface (equivalent to ≈0.2° diameter) in a focal plane located in front of the instrument. The product of both distributions at different radii was 1.00, 1.00, 0.90, 0.80, and 0.20 at 0°, 0.25°, 0.50°, 0.75°, and 1.00°, respectively.
  38. The conversion factor used in this study was slightly larger than that calculated by using Eq. (10) from other MP spectra cited in the literature. A difference was found of 1% for the spectrum of a mixture of liposome-bound lutein and zeaxanthin in Bone et al.,4of 5% for the psychophysically determined spectrum in Wyszecki and Stiles,5and of 6% for the spectrum in fixed primate retinas obtained by microspectrometry in Snodderly et al.3
  39. J. S. Werner, B. R. Wooten, “Opponent chromatic mechanisms: relation to photopigments and hue naming,” J. Opt. Soc. Am. 69, 422–434 (1979).
    [CrossRef] [PubMed]
  40. B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Cigarette smoking and retinal carotenoids: implications for agre-related macular degeneration,” Vision Res. 36, 3003–3009 (1996).
    [CrossRef] [PubMed]
  41. B. R. Hammond, J. Curran-Celentano, S. Judd, K. Fuld, N. I. Krinsky, B. R. Wooten, D. M. Snodderly, “Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns,” Vision Res. 36, 2001–2012 (1996).
    [CrossRef] [PubMed]
  42. B. R. Hammond, K. Fuld, D. M. Snodderly, “Iris color and macular pigment optical density,” Exp. Eye Res. 62, 293–297 (1996).
    [CrossRef] [PubMed]
  43. We assume that the MP distribution D(r)is exponential12,17and that it is given by D(r)=D(0)10-2 log(2)(r/FWHM),where r is the distance to the center. To convert DHFPestimated with a 0.8°-diameter field to equivalent values for a 2° test field, we further assumed that the peak density D(0)and the full width at half-maximum (FWHM) were linked by the experimentally derived relation D(0)=0.13+0.22FWHM.17 Using various values of FWHM, we obtained a nonlinear relationship between the densities for the 2°- and the 0.8°-diameter field: D2=-0.03+0.31D0.8+1.14D0.82(for D0.8<0.8 D.U.). Tp predict the densities DAFmeasured by the AF method (test field of radius R), we calculate DAF=log∑0RA(r)P(r)rΔr-log∑0RA(r)P(r)10-D(r)rΔr, where P(r)is the distribution of fundus AF in the absence of MP and A(r)is the product of the distribution of retinal irradiance and sensitivity of the fluorometer. Densities DAFwere computed with a constant P(r),the measured distribution A(r),37and an increment of r=0.005°.
  44. Most older subjects in this study and subjects in the study of Hammond et al.16were recruited from the Harvard Cooperative Program on Aging (Roslindale, Mass.), an organization devoted to good health through research and education.
  45. A. Stockman, L. T. Sharpe, “The spectral sensitivities of the middle- and long-wavelength-sensitive cones derived from measurements in observers of known genotype,” Vision Res. 40, 1711–1737 (2000).
    [CrossRef] [PubMed]
  46. S. A. Burns, A. E. Elsner, “Color matching at high illuminances: photopigment optical density and pupil entry,” J. Opt. Soc. Am. A 10, 221–230 (1993).
    [CrossRef] [PubMed]
  47. V. C. Smith, J. Pokorny, S. J. Starr, “Variability of color mixture data—I. Interobserver variability in the unit coordinates,” Vision Res. 16, 1087–1094 (1976).
    [CrossRef]
  48. S. A. Hagstrom, J. Neitz, M. Neitz, Ratio of M/L Pigment Gene Expression Decreases with Retinal Eccentricity (Kluwer Academic, Dordrecht, The Netherlands, 1997), pp. 59–66.
  49. A. E. Elsner, S. A. Burns, R. H. Webb, “Mapping cone photopigment optical density,” J. Opt. Soc. Am. A 10, 52–58 (1993).
    [CrossRef] [PubMed]
  50. W. H. Swanson, G. E. Fish, “Age-related changes in the color-match-area effect,” Vision Res. 36, 2079–2085 (1996).
    [CrossRef] [PubMed]
  51. J.-M. Gorrand, R. Alfieri, J.-Y. Boire, “Diffusion of the retinal layers of the living human eye,” Vision Res. 24, 1097–1106 (1984).
    [CrossRef] [PubMed]
  52. S. A. Burns, S. Wu, F. Delori, A. E. Elsner, “Direct measurement of human-cone-photoreceptor alignment,” J. Opt. Soc. Am. A 12, 2329–2338 (1995).
    [CrossRef]
  53. P. J. Delint, T. Berendschot, D. van Norren, “Local photoreceptor alignment measured with a scanning laser ophthalmoscope,” Vision Res. 37, 243–248 (1997).
    [CrossRef] [PubMed]
  54. L. Feeney-Burns, E. S. Hilderbrand, S. Eldridge, “Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells,” Invest. Ophthalmol. Visual Sci. 25, 195–200 (1984).
  55. J. J. Weiter, F. C. Delori, G. Wing, K. A. Fitch, “Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes,” Invest. Ophthalmol. Visual Sci. 27, 145–152 (1986).
  56. V.-P. Gabel, R. Birngruber, F. Hillenkamp, “Visible and near infrared light absorption in pigment epithelium and choroid,” in XXIII Concilium Ophthalmol Kyoto, Exerpta Medica, K. Shimuzu, J. A. Osterhuis, eds. (Oxford, Amsterdam, 1978), Vol. 14, pp. 658–662.
  57. O. W. van Assendelft, Spectroscopy of Hemoglobin Derivatives (Thomas, Springfield, Ill., 1970).
  58. Ex vivo data from the paper of Weiter et al.55for RPE melanin was multiplied by 2.2 to account for the fact that melanin transmission in that study was measured in the 500–600-nm spectral range and is expressed here at 460 nm. Mean melanin densities at 460 nm for single pass through the RPE were computed as 0.56±0.19and 0.31±0.10 D.U.for the fovea and for sites at 6°–7° on either side of the fovea, respectively. Mean density difference in melanin between both sites was 0.25±0.15 D.U.
  59. M. D. Boulton, F. Docchio, F. Dayhaw-Barker, P. Ramponi, R. Cubeddu, “Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium,” Vision Res. 30, 1291–1303 (1990).
    [CrossRef] [PubMed]
  60. S. Y. Schmidt, R. D. Peisch, “Melanin concentration in normal human retinal pigment epithelium,” Invest. Ophthalmol. Visual Sci. 27, 1063–1067 (1986).
  61. Ex vivo measurements in sections of RPE showed that lipofuscin fluorescence at the fovea was 81%±14%of that at the perifovea.55 This ratio was calculated from the fluorescence measurements in sections of the RPE (bleached melanin) and from RPE cell heights at both sites. In vivo fluorescence at the fovea, measured with Λ=550 nm(no MP absorption), was on average 64%±10% of that at the perifovea. If we assume that the difference between these ratios results from a higher apical melanin absorption at the fovea, then we can calculate that the melanin density difference is log(64/81)/[Kme(550)+Kme(710)]or 0.14±0.14 D.U.at 460 nm.
  62. G. E. Eldred, M. L. Katz, “Fluorophores of the human retinal pigment epithelium: separation and spectral characterization,” Exp. Eye Res. 47, 71–86 (1988).
    [CrossRef] [PubMed]
  63. F. C. Delori, “RPE lipofuscin in aging and age related macular degeneration,” in Retinal Pigment Epithelium and Macular Diseases, F. C. Piccolino, G. Coscas, eds. (Kluwer Academic, Dordrecht, The Netherlands, 1998), pp. 37–45.
  64. A. E. Elsner, S. A. Burns, J. J. Weiter, F. C. Delori, “Infrared imaging of sub-retinal structures in the human ocular fundus,” Vision Res. 36, 191–205 (1996).
    [CrossRef] [PubMed]
  65. D. M. Snodderly, R. S. Weinhaus, J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12, 1169–1193 (1992).
    [PubMed]
  66. Fluorescence F′and reflectance R′incorporate absolute corrections to account for ocular media absorption. This combines our individually determined lens densities, which are relative to the density of a 44-year-old average observer,35 and mean lens densities at age 44 years from Pokorny et al.67 Average media-corrected fluorescences F′ and reflectances R′ at the fovea (F) and at the perifovea (P) were (n=159)At F:  FF′(470, 710)=81±44 AFUFF′(550, 710)=136±62 AFUAt P:  FP′(470, 710)=310±129 AFUFP′(550, 710)=214±91 AFUAt F:  RF′(470)=0.61%±0.26%RF′(550)=1.66%±0.61%At P:  RP′(470)=2.74%±0.89%RP′(550)=3.10%±0.91% The AF unit AFU is nJ nm-1 sr-1/J.
  67. J. Pokorny, V. C. Smith, M. Lutze, “Aging of the human lens,” Appl. Opt. 26, 1437–1440 (1987).
    [CrossRef] [PubMed]
  68. Crystalline lens AF was measured in three study subjects (ages: 37, 46, and 57 years) by focusing the sampling volume within the lens (using an additional ophthalmic lens). Excitation spectra decreased by 76%±3%between 470 and 550 nm. Emission spectra were maximal at 520±5 nmfor Λ=470 nmand decreased to 10% of that maximum fluorescence at 655±8 nm. Fluorescence intensity increased with age of the three subjects.
  69. R. B. Kurzel, M. L. Wolbarsht, B. S. Yamanashi, “Spectral studies on normal and cataractous intact human lenses,” Exp. Eye Res. 17, 65–71 (1973).
    [CrossRef] [PubMed]
  70. N. Ueno, B. Chakrabarti, “Liquefaction of human vitreous in model aphakic eyes by 300-nm UV photolysis: monitoring liquefaction by fluorescence,” Curr. Eye Res. 9, 487–492 (1990).
    [CrossRef] [PubMed]
  71. B. Chance, B. Schoener, R. Oshino, F. Itshak, Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples,” J. Biol. Chem. 254, 4764–4771 (1979).
    [PubMed]
  72. By rewriting relation (20) for two-emission wavelengths, λ=620 nmand λ=λdet,and assuming that Sais small compared with the foveal fluorescence and that its emission decreases exponentially, we can show that ΔD∝Sa(470, 620){1-[FF′(470, 620)/FF′(470, λdet)]exp[-α(λdet-620)]}.The measure ΔDis then proportional to Saand increases in a quasi-exponential manner with increasing λdettoward the true value (as sketched in the top of Fig. 10). By performing detailed fits for a number of subjects, we estimated that the amount of underestimation is approximately 1/3 of ΔD.
  73. A. von Ruckmann, F. W. Fitzke, A. C. Bird, “Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope,” Invest. Ophthalmol. Visual Sci. 38, 478–486 (1997).
  74. J. M. Gorrand, F. C. Delori, “Reflectance and curvature of the inner limiting membrane at the foveola,” J. Opt. Soc. Am. A 16, 1229–1237 (1999).
    [CrossRef]
  75. M. J. Hogan, J. A. Alvarado, J. E. Weddell, Histology of the Human Eye (Saunders, Philadelphia, Pa., 1971).
  76. T. Gillbro, R. J. Cogdell, “Carotenoid fluorescence,” Chem. Phys. Lett. 158, 312–316 (1989).
    [CrossRef]
  77. Reflectances Raare positively correlated with age (r=0.4,p<0.0001) as a direct result of the increase with age of media-corrected reflectances RF′(470).This increase in reflectance cannot be accounted for by known age-related retinal changes. As we mentioned before,35we believe that this increase may result from a slight overestimation of our media correction method.
  78. The foveal fluorescence FF′in relation (21) was expressed as a function of the reflectance RF*of layers posterior to the MP [as in Eq. (6)] by RF′(λ)=Ra(λ)+RF*(λ)10-2Kmp(λ)DAF,c(460).The parameter Ra/RF*is then the single free parameter in the fits.
  79. D. van Norren, personal communication (Human Factors Research Institute, P.O. Box 23, Soesterberg, 3769ZG, The Netherlands, 1999).
  80. S. A. Burns, S. Marcos, J. S. McLellan, A. E. Elsner, “Reflectometric measurement of cone directionality and photopigment optical density,” Invest. Ophthalmol. Visual Sci. 40, S365 (1999) (ARVO Abstract No. 1935).
  81. P. J. DeLint, T. T. Berendschot, J. van de Kraats, D. van Norren, “Slow optical changes in human photoreceptors induced by light,” Invest. Ophthalmol. Visual Sci. 41, 282–289 (2000).
  82. P. M. Prieto, S. A. Burns, J. S. McLellan, “Single pass optical density measurements by means of the lipofuscin fluorescence,” Invest. Ophthalmol. Visual Sci. 40, S429 (2000) (ARVO Abstract No. 2271-B517).
  83. Direct measurements74of the ILM reflectance ρ used a perfect mirror as reference (with curvature equal to that found in the eye). To convert this reflectance into an equivalent reflectance (reference: perfect diffuser),34we used Eqs. (27) and (28) of Gorrand and Delori’s paper.74The equivalent reflectance of the ILM is then RILM=(πρr2)/(4A),where the reflectance is ρ=0041 %±0.0019 %(seven young subjects), ris the radius of curvature of the foveal depression (r=1.22±0.22 mm),and A is the area of the retinal test field (0.26 mm2for a 2°-diameter field). Using the original data (n=7, ages: 16–26 years), we found that RILM=0.019 %±0.013 % (range: 0.007%–0.04%).
  84. R. A. Bone, J. T. Landrum, “Macular pigment in Henle fiber membranes: a model for Haidinger’s brushes,” Vision Res. 24, 103–108 (1984).
    [CrossRef]
  85. R. W. Knighton, X.-R. Huang, “Directional and spectral reflectance of the rat retinal nerve fiber layer,” Invest. Ophthalmol. Visual Sci. 40, 639–647 (1999).
  86. R. W. Knighton, Q. Zhou, “The relationship between the reflectance and thickness of the retinal nerve fiber layer,” J. Glaucoma 4, 117–123 (1995).
    [CrossRef] [PubMed]
  87. F. C. Delori, D. G. Goger, B. R. Hammond, D. M. Snodderly, S. A. Burns, “Foveal lipofuscin and macular pigment,” Invest. Ophthalmol. Visual Sci. 38, S591 (1997) (ARVO Abstract No. 1657).

2000 (5)

P. S. Bernstein, D. Y. Zhao, R. W. Ermakov, R. W. McClane, W. Gellermann, “Resonance Raman measurements of macular pigment levels in the living human retina,” Invest. Ophthalmol. Visual Sci. 40, B283 (2000) (ARVO Abstract No. 3185).

B. R. Hammond, M. Caruso-Avery, “Macular pigment optical density in a Southwestern sample,” Invest. Ophthalmol. Visual Sci. 41, 1492–1497 (2000).

A. Stockman, L. T. Sharpe, “The spectral sensitivities of the middle- and long-wavelength-sensitive cones derived from measurements in observers of known genotype,” Vision Res. 40, 1711–1737 (2000).
[CrossRef] [PubMed]

P. J. DeLint, T. T. Berendschot, J. van de Kraats, D. van Norren, “Slow optical changes in human photoreceptors induced by light,” Invest. Ophthalmol. Visual Sci. 41, 282–289 (2000).

P. M. Prieto, S. A. Burns, J. S. McLellan, “Single pass optical density measurements by means of the lipofuscin fluorescence,” Invest. Ophthalmol. Visual Sci. 40, S429 (2000) (ARVO Abstract No. 2271-B517).

1999 (5)

R. W. Knighton, X.-R. Huang, “Directional and spectral reflectance of the rat retinal nerve fiber layer,” Invest. Ophthalmol. Visual Sci. 40, 639–647 (1999).

J. M. Gorrand, F. C. Delori, “Reflectance and curvature of the inner limiting membrane at the foveola,” J. Opt. Soc. Am. A 16, 1229–1237 (1999).
[CrossRef]

S. A. Burns, S. Marcos, J. S. McLellan, A. E. Elsner, “Reflectometric measurement of cone directionality and photopigment optical density,” Invest. Ophthalmol. Visual Sci. 40, S365 (1999) (ARVO Abstract No. 1935).

S. Beatty, M. Boulton, D. Henson, H. H. Koh, I. J. Murray, “Macular pigment and age related macular degeneration,” Br. J. Ophthamol. 83, 867–877 (1999).
[CrossRef]

T. Berendschot, J. van de Kraats, D. van Norren, “Three methods to measure macular pigment compared in a lutein intake study,” Invest. Ophthalmol. Visual Sci. 39, S314 (1999) [Association for Research in Vision and Ophthalmology (ARVO) Abstract No. 1665].

1998 (2)

A. E. Elsner, S. A. Burns, E. Beausencourt, J. J. Weiter, “Foveal cone photopigment distribution: small alterations associated with macular pigment distribution,” Invest. Ophthalmol. Visual Sci. 39, 2394–2404 (1998).

P. S. Bernstein, M. D. Yoshida, N. B. Katz, R. W. McClane, W. Gellermann, “Raman detection of macular carotenoid pigments in intact human retina,” Invest. Ophthalmol. Visual Sci. 39, 2003–2011 (1998).

1997 (7)

P. J. Delint, T. Berendschot, D. van Norren, “Local photoreceptor alignment measured with a scanning laser ophthalmoscope,” Vision Res. 37, 243–248 (1997).
[CrossRef] [PubMed]

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Density of the human crystalline lens is related to the macular pigment carotenoids, lutein and zeaxanthin,” Optom. Vision Sci. 74, 499–504 (1997).
[CrossRef]

B. R. Hammond, E. J. Johnson, R. M. Russell, N. I. Krinsky, K. J. Yeum, R. B. Edwards, D. M. Snodderly, “Dietary modification of human macular pigment density,” Invest. Ophthalmol. Visual Sci. 38, 1795–1801 (1997).

J. T. Landrum, R. A. Bone, H. Joa, M. D. Kilburn, L. L. Moore, K. E. Sprague, “One year study of the macular pigment: the effect of 140 days of a lutein supplement,” Exp. Eye Res. 65, 57–62 (1997).
[CrossRef] [PubMed]

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Individual variations in the spatial profile of human macular pigment,” J. Opt. Soc. Am. A 14, 1187–1196 (1997).
[CrossRef]

F. C. Delori, D. G. Goger, B. R. Hammond, D. M. Snodderly, S. A. Burns, “Foveal lipofuscin and macular pigment,” Invest. Ophthalmol. Visual Sci. 38, S591 (1997) (ARVO Abstract No. 1657).

A. von Ruckmann, F. W. Fitzke, A. C. Bird, “Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope,” Invest. Ophthalmol. Visual Sci. 38, 478–486 (1997).

1996 (8)

W. H. Swanson, G. E. Fish, “Age-related changes in the color-match-area effect,” Vision Res. 36, 2079–2085 (1996).
[CrossRef] [PubMed]

F. C. Delori, S. A. Burns, “Fundus reflectance and the measurement of crystalline lens density,” J. Opt. Soc. Am. A 13, 215–226 (1996).
[CrossRef]

J. van de Kraats, T. T. J. M. Berendschot, D. van Norren, “The pathways of light measured in fundus reflectometry,” Vision Res. 36, 2229–2247 (1996).
[CrossRef] [PubMed]

A. E. Elsner, S. A. Burns, J. J. Weiter, F. C. Delori, “Infrared imaging of sub-retinal structures in the human ocular fundus,” Vision Res. 36, 191–205 (1996).
[CrossRef] [PubMed]

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Cigarette smoking and retinal carotenoids: implications for agre-related macular degeneration,” Vision Res. 36, 3003–3009 (1996).
[CrossRef] [PubMed]

B. R. Hammond, J. Curran-Celentano, S. Judd, K. Fuld, N. I. Krinsky, B. R. Wooten, D. M. Snodderly, “Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns,” Vision Res. 36, 2001–2012 (1996).
[CrossRef] [PubMed]

B. R. Hammond, K. Fuld, D. M. Snodderly, “Iris color and macular pigment optical density,” Exp. Eye Res. 62, 293–297 (1996).
[CrossRef] [PubMed]

D. Schweitzer, M. Hammer, M. Scibor, “Imaging spectrometry in ophthalmology—principle and applications in microcirculation and in investigation of pigments,” Ophthalm. Res. 28, 37–44 (1996).
[CrossRef]

1995 (5)

D. M. Snodderly, “Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins,” Am. J. Clin. Nutr. 62(supplement), 1448S–1461S (1995).
[PubMed]

B. R. Hammond, K. Fuld, J. Curran-Celentano, “Macular pigment density in monozygotic twins,” Invest. Ophthalmol. Visual Sci. 36, 2531–2541 (1995).

S. A. Burns, S. Wu, F. Delori, A. E. Elsner, “Direct measurement of human-cone-photoreceptor alignment,” J. Opt. Soc. Am. A 12, 2329–2338 (1995).
[CrossRef]

R. W. Knighton, Q. Zhou, “The relationship between the reflectance and thickness of the retinal nerve fiber layer,” J. Glaucoma 4, 117–123 (1995).
[CrossRef] [PubMed]

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

1994 (2)

F. C. Delori, “Spectrophotometer for noninvasive measurement of intrinsic fluorescence and reflectance of the ocular fundus,” Appl. Opt. 33, 7439–7452 (1994).
[CrossRef] [PubMed]

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

1993 (2)

1992 (3)

B. Hammond, K. Fuld, “Interocular differences in macular pigment density,” Invest. Ophthalmol. Visual Sci. 33, 350–355 (1992).

R. A. Bone, J. T. Landrum, A. Cains, “Optical density spectra of the macular pigment in vivo and in vitro,” Vision Res. 32, 105–110 (1992).
[CrossRef] [PubMed]

D. M. Snodderly, R. S. Weinhaus, J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12, 1169–1193 (1992).
[PubMed]

1990 (2)

M. D. Boulton, F. Docchio, F. Dayhaw-Barker, P. Ramponi, R. Cubeddu, “Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium,” Vision Res. 30, 1291–1303 (1990).
[CrossRef] [PubMed]

N. Ueno, B. Chakrabarti, “Liquefaction of human vitreous in model aphakic eyes by 300-nm UV photolysis: monitoring liquefaction by fluorescence,” Curr. Eye Res. 9, 487–492 (1990).
[CrossRef] [PubMed]

1989 (3)

T. Gillbro, R. J. Cogdell, “Carotenoid fluorescence,” Chem. Phys. Lett. 158, 312–316 (1989).
[CrossRef]

F. C. Delori, K. P. Pflibsen, “Spectral reflectance of the human ocular fundus,” Appl. Opt. 28, 1061–1077 (1989).
[CrossRef] [PubMed]

P. E. Kilbride, K. R. Alexander, M. Fishman, G. A. Fishman, “Human macular pigment assessed by imaging fundus reflectometry,” Vision Res. 29, 663–674 (1989).
[CrossRef] [PubMed]

1988 (2)

G. J. Handelman, E. A. Dratz, C. C. Reay, F. J. G. M. van Kuijk, “Carotenoids in the human macula and whole retina,” Invest. Ophthalmol. Visual Sci. 29, 850–855 (1988).

G. E. Eldred, M. L. Katz, “Fluorophores of the human retinal pigment epithelium: separation and spectral characterization,” Exp. Eye Res. 47, 71–86 (1988).
[CrossRef] [PubMed]

1987 (3)

J. S. Werner, S. K. Donnelly, R. Kliegel, “Aging and human macular pigment density,” Vision Res. 27, 257–268 (1987).
[CrossRef]

P. L. Pease, A. J. Adams, E. Nuccio, “Optical density of human macular pigment,” Vision Res. 27, 705–710 (1987).
[CrossRef] [PubMed]

J. Pokorny, V. C. Smith, M. Lutze, “Aging of the human lens,” Appl. Opt. 26, 1437–1440 (1987).
[CrossRef] [PubMed]

1986 (3)

J. J. Weiter, F. C. Delori, G. Wing, K. A. Fitch, “Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes,” Invest. Ophthalmol. Visual Sci. 27, 145–152 (1986).

S. Y. Schmidt, R. D. Peisch, “Melanin concentration in normal human retinal pigment epithelium,” Invest. Ophthalmol. Visual Sci. 27, 1063–1067 (1986).

D. van Norren, L. F. Tiemeijer, “Spectral reflectance of the human eye,” Vision Res. 26, 313–320 (1986).
[CrossRef] [PubMed]

1984 (5)

L. Feeney-Burns, E. S. Hilderbrand, S. Eldridge, “Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells,” Invest. Ophthalmol. Visual Sci. 25, 195–200 (1984).

D. M. Snodderly, J. D. Auran, F. C. Delori, “The macular pigment. II. Spatial distribution in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 674–684 (1984).

D. M. Snodderly, P. K. Brown, F. C. Delori, J. D. Auran, “The macular pigment. I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 660–673 (1984).

R. A. Bone, J. T. Landrum, “Macular pigment in Henle fiber membranes: a model for Haidinger’s brushes,” Vision Res. 24, 103–108 (1984).
[CrossRef]

J.-M. Gorrand, R. Alfieri, J.-Y. Boire, “Diffusion of the retinal layers of the living human eye,” Vision Res. 24, 1097–1106 (1984).
[CrossRef] [PubMed]

1979 (2)

B. Chance, B. Schoener, R. Oshino, F. Itshak, Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples,” J. Biol. Chem. 254, 4764–4771 (1979).
[PubMed]

J. S. Werner, B. R. Wooten, “Opponent chromatic mechanisms: relation to photopigments and hue naming,” J. Opt. Soc. Am. 69, 422–434 (1979).
[CrossRef] [PubMed]

1976 (1)

V. C. Smith, J. Pokorny, S. J. Starr, “Variability of color mixture data—I. Interobserver variability in the unit coordinates,” Vision Res. 16, 1087–1094 (1976).
[CrossRef]

1973 (1)

R. B. Kurzel, M. L. Wolbarsht, B. S. Yamanashi, “Spectral studies on normal and cataractous intact human lenses,” Exp. Eye Res. 17, 65–71 (1973).
[CrossRef] [PubMed]

1952 (1)

G. S. Brindley, E. N. Willmer, “The reflection of light from the macular and peripheral fundus oculi in man,” J. Physiol. (London) 116, 350–356 (1952).

Adams, A. J.

P. L. Pease, A. J. Adams, E. Nuccio, “Optical density of human macular pigment,” Vision Res. 27, 705–710 (1987).
[CrossRef] [PubMed]

Ajani, U. A.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Alexander, K. R.

P. E. Kilbride, K. R. Alexander, M. Fishman, G. A. Fishman, “Human macular pigment assessed by imaging fundus reflectometry,” Vision Res. 29, 663–674 (1989).
[CrossRef] [PubMed]

Alfieri, R.

J.-M. Gorrand, R. Alfieri, J.-Y. Boire, “Diffusion of the retinal layers of the living human eye,” Vision Res. 24, 1097–1106 (1984).
[CrossRef] [PubMed]

Alvarado, J. A.

M. J. Hogan, J. A. Alvarado, J. E. Weddell, Histology of the Human Eye (Saunders, Philadelphia, Pa., 1971).

Arend, O.

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

Auran, J. D.

D. M. Snodderly, J. D. Auran, F. C. Delori, “The macular pigment. II. Spatial distribution in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 674–684 (1984).

D. M. Snodderly, P. K. Brown, F. C. Delori, J. D. Auran, “The macular pigment. I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 660–673 (1984).

Beatty, S.

S. Beatty, M. Boulton, D. Henson, H. H. Koh, I. J. Murray, “Macular pigment and age related macular degeneration,” Br. J. Ophthamol. 83, 867–877 (1999).
[CrossRef]

Beausencourt, E.

A. E. Elsner, S. A. Burns, E. Beausencourt, J. J. Weiter, “Foveal cone photopigment distribution: small alterations associated with macular pigment distribution,” Invest. Ophthalmol. Visual Sci. 39, 2394–2404 (1998).

Berendschot, T.

T. Berendschot, J. van de Kraats, D. van Norren, “Three methods to measure macular pigment compared in a lutein intake study,” Invest. Ophthalmol. Visual Sci. 39, S314 (1999) [Association for Research in Vision and Ophthalmology (ARVO) Abstract No. 1665].

P. J. Delint, T. Berendschot, D. van Norren, “Local photoreceptor alignment measured with a scanning laser ophthalmoscope,” Vision Res. 37, 243–248 (1997).
[CrossRef] [PubMed]

Berendschot, T. T.

P. J. DeLint, T. T. Berendschot, J. van de Kraats, D. van Norren, “Slow optical changes in human photoreceptors induced by light,” Invest. Ophthalmol. Visual Sci. 41, 282–289 (2000).

Berendschot, T. T. J. M.

J. van de Kraats, T. T. J. M. Berendschot, D. van Norren, “The pathways of light measured in fundus reflectometry,” Vision Res. 36, 2229–2247 (1996).
[CrossRef] [PubMed]

Bernstein, P. S.

P. S. Bernstein, D. Y. Zhao, R. W. Ermakov, R. W. McClane, W. Gellermann, “Resonance Raman measurements of macular pigment levels in the living human retina,” Invest. Ophthalmol. Visual Sci. 40, B283 (2000) (ARVO Abstract No. 3185).

P. S. Bernstein, M. D. Yoshida, N. B. Katz, R. W. McClane, W. Gellermann, “Raman detection of macular carotenoid pigments in intact human retina,” Invest. Ophthalmol. Visual Sci. 39, 2003–2011 (1998).

Bird, A. C.

A. von Ruckmann, F. W. Fitzke, A. C. Bird, “Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope,” Invest. Ophthalmol. Visual Sci. 38, 478–486 (1997).

Birngruber, R.

V.-P. Gabel, R. Birngruber, F. Hillenkamp, “Visible and near infrared light absorption in pigment epithelium and choroid,” in XXIII Concilium Ophthalmol Kyoto, Exerpta Medica, K. Shimuzu, J. A. Osterhuis, eds. (Oxford, Amsterdam, 1978), Vol. 14, pp. 658–662.

Blair, N.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Boire, J.-Y.

J.-M. Gorrand, R. Alfieri, J.-Y. Boire, “Diffusion of the retinal layers of the living human eye,” Vision Res. 24, 1097–1106 (1984).
[CrossRef] [PubMed]

Bone, R. A.

J. T. Landrum, R. A. Bone, H. Joa, M. D. Kilburn, L. L. Moore, K. E. Sprague, “One year study of the macular pigment: the effect of 140 days of a lutein supplement,” Exp. Eye Res. 65, 57–62 (1997).
[CrossRef] [PubMed]

R. A. Bone, J. T. Landrum, A. Cains, “Optical density spectra of the macular pigment in vivo and in vitro,” Vision Res. 32, 105–110 (1992).
[CrossRef] [PubMed]

R. A. Bone, J. T. Landrum, “Macular pigment in Henle fiber membranes: a model for Haidinger’s brushes,” Vision Res. 24, 103–108 (1984).
[CrossRef]

Boulton, M.

S. Beatty, M. Boulton, D. Henson, H. H. Koh, I. J. Murray, “Macular pigment and age related macular degeneration,” Br. J. Ophthamol. 83, 867–877 (1999).
[CrossRef]

Boulton, M. D.

M. D. Boulton, F. Docchio, F. Dayhaw-Barker, P. Ramponi, R. Cubeddu, “Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium,” Vision Res. 30, 1291–1303 (1990).
[CrossRef] [PubMed]

Brindley, G. S.

G. S. Brindley, E. N. Willmer, “The reflection of light from the macular and peripheral fundus oculi in man,” J. Physiol. (London) 116, 350–356 (1952).

Brown, P. K.

D. M. Snodderly, P. K. Brown, F. C. Delori, J. D. Auran, “The macular pigment. I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 660–673 (1984).

Burns, S. A.

P. M. Prieto, S. A. Burns, J. S. McLellan, “Single pass optical density measurements by means of the lipofuscin fluorescence,” Invest. Ophthalmol. Visual Sci. 40, S429 (2000) (ARVO Abstract No. 2271-B517).

S. A. Burns, S. Marcos, J. S. McLellan, A. E. Elsner, “Reflectometric measurement of cone directionality and photopigment optical density,” Invest. Ophthalmol. Visual Sci. 40, S365 (1999) (ARVO Abstract No. 1935).

A. E. Elsner, S. A. Burns, E. Beausencourt, J. J. Weiter, “Foveal cone photopigment distribution: small alterations associated with macular pigment distribution,” Invest. Ophthalmol. Visual Sci. 39, 2394–2404 (1998).

F. C. Delori, D. G. Goger, B. R. Hammond, D. M. Snodderly, S. A. Burns, “Foveal lipofuscin and macular pigment,” Invest. Ophthalmol. Visual Sci. 38, S591 (1997) (ARVO Abstract No. 1657).

A. E. Elsner, S. A. Burns, J. J. Weiter, F. C. Delori, “Infrared imaging of sub-retinal structures in the human ocular fundus,” Vision Res. 36, 191–205 (1996).
[CrossRef] [PubMed]

F. C. Delori, S. A. Burns, “Fundus reflectance and the measurement of crystalline lens density,” J. Opt. Soc. Am. A 13, 215–226 (1996).
[CrossRef]

S. A. Burns, S. Wu, F. Delori, A. E. Elsner, “Direct measurement of human-cone-photoreceptor alignment,” J. Opt. Soc. Am. A 12, 2329–2338 (1995).
[CrossRef]

S. A. Burns, A. E. Elsner, “Color matching at high illuminances: photopigment optical density and pupil entry,” J. Opt. Soc. Am. A 10, 221–230 (1993).
[CrossRef] [PubMed]

A. E. Elsner, S. A. Burns, R. H. Webb, “Mapping cone photopigment optical density,” J. Opt. Soc. Am. A 10, 52–58 (1993).
[CrossRef] [PubMed]

Burton, T. C.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Cains, A.

R. A. Bone, J. T. Landrum, A. Cains, “Optical density spectra of the macular pigment in vivo and in vitro,” Vision Res. 32, 105–110 (1992).
[CrossRef] [PubMed]

Caruso-Avery, M.

B. R. Hammond, M. Caruso-Avery, “Macular pigment optical density in a Southwestern sample,” Invest. Ophthalmol. Visual Sci. 41, 1492–1497 (2000).

Chakrabarti, B.

N. Ueno, B. Chakrabarti, “Liquefaction of human vitreous in model aphakic eyes by 300-nm UV photolysis: monitoring liquefaction by fluorescence,” Curr. Eye Res. 9, 487–492 (1990).
[CrossRef] [PubMed]

Chance, B.

B. Chance, B. Schoener, R. Oshino, F. Itshak, Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples,” J. Biol. Chem. 254, 4764–4771 (1979).
[PubMed]

Choi, J. C.

D. M. Snodderly, R. S. Weinhaus, J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12, 1169–1193 (1992).
[PubMed]

Cogdell, R. J.

T. Gillbro, R. J. Cogdell, “Carotenoid fluorescence,” Chem. Phys. Lett. 158, 312–316 (1989).
[CrossRef]

Cubeddu, R.

M. D. Boulton, F. Docchio, F. Dayhaw-Barker, P. Ramponi, R. Cubeddu, “Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium,” Vision Res. 30, 1291–1303 (1990).
[CrossRef] [PubMed]

Curran-Celentano, J.

B. R. Hammond, J. Curran-Celentano, S. Judd, K. Fuld, N. I. Krinsky, B. R. Wooten, D. M. Snodderly, “Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns,” Vision Res. 36, 2001–2012 (1996).
[CrossRef] [PubMed]

B. R. Hammond, K. Fuld, J. Curran-Celentano, “Macular pigment density in monozygotic twins,” Invest. Ophthalmol. Visual Sci. 36, 2531–2541 (1995).

Dayhaw-Barker, F.

M. D. Boulton, F. Docchio, F. Dayhaw-Barker, P. Ramponi, R. Cubeddu, “Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium,” Vision Res. 30, 1291–1303 (1990).
[CrossRef] [PubMed]

DeLint, P. J.

P. J. DeLint, T. T. Berendschot, J. van de Kraats, D. van Norren, “Slow optical changes in human photoreceptors induced by light,” Invest. Ophthalmol. Visual Sci. 41, 282–289 (2000).

P. J. Delint, T. Berendschot, D. van Norren, “Local photoreceptor alignment measured with a scanning laser ophthalmoscope,” Vision Res. 37, 243–248 (1997).
[CrossRef] [PubMed]

Delori, F.

Delori, F. C.

J. M. Gorrand, F. C. Delori, “Reflectance and curvature of the inner limiting membrane at the foveola,” J. Opt. Soc. Am. A 16, 1229–1237 (1999).
[CrossRef]

F. C. Delori, D. G. Goger, B. R. Hammond, D. M. Snodderly, S. A. Burns, “Foveal lipofuscin and macular pigment,” Invest. Ophthalmol. Visual Sci. 38, S591 (1997) (ARVO Abstract No. 1657).

A. E. Elsner, S. A. Burns, J. J. Weiter, F. C. Delori, “Infrared imaging of sub-retinal structures in the human ocular fundus,” Vision Res. 36, 191–205 (1996).
[CrossRef] [PubMed]

F. C. Delori, S. A. Burns, “Fundus reflectance and the measurement of crystalline lens density,” J. Opt. Soc. Am. A 13, 215–226 (1996).
[CrossRef]

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

F. C. Delori, “Spectrophotometer for noninvasive measurement of intrinsic fluorescence and reflectance of the ocular fundus,” Appl. Opt. 33, 7439–7452 (1994).
[CrossRef] [PubMed]

F. C. Delori, K. P. Pflibsen, “Spectral reflectance of the human ocular fundus,” Appl. Opt. 28, 1061–1077 (1989).
[CrossRef] [PubMed]

J. J. Weiter, F. C. Delori, G. Wing, K. A. Fitch, “Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes,” Invest. Ophthalmol. Visual Sci. 27, 145–152 (1986).

D. M. Snodderly, J. D. Auran, F. C. Delori, “The macular pigment. II. Spatial distribution in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 674–684 (1984).

D. M. Snodderly, P. K. Brown, F. C. Delori, J. D. Auran, “The macular pigment. I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 660–673 (1984).

F. C. Delori, “RPE lipofuscin in aging and age related macular degeneration,” in Retinal Pigment Epithelium and Macular Diseases, F. C. Piccolino, G. Coscas, eds. (Kluwer Academic, Dordrecht, The Netherlands, 1998), pp. 37–45.

F. C. Delori, “Macular pigment density measured by reflectometry and fluorophotometry,” in Opthalmic and Visual Optics and Noninvasive Assessment of the Visual System, Vol. 3 of 1993 OSA Technical Digest Series (Optical Society of America, Washington D.C., 1993), pp. 240–243.

Docchio, F.

M. D. Boulton, F. Docchio, F. Dayhaw-Barker, P. Ramponi, R. Cubeddu, “Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium,” Vision Res. 30, 1291–1303 (1990).
[CrossRef] [PubMed]

Donnelly, S. K.

J. S. Werner, S. K. Donnelly, R. Kliegel, “Aging and human macular pigment density,” Vision Res. 27, 257–268 (1987).
[CrossRef]

Dorey, C. K.

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

Dratz, E. A.

G. J. Handelman, E. A. Dratz, C. C. Reay, F. J. G. M. van Kuijk, “Carotenoids in the human macula and whole retina,” Invest. Ophthalmol. Visual Sci. 29, 850–855 (1988).

Edwards, R. B.

B. R. Hammond, E. J. Johnson, R. M. Russell, N. I. Krinsky, K. J. Yeum, R. B. Edwards, D. M. Snodderly, “Dietary modification of human macular pigment density,” Invest. Ophthalmol. Visual Sci. 38, 1795–1801 (1997).

Eldred, G. E.

G. E. Eldred, M. L. Katz, “Fluorophores of the human retinal pigment epithelium: separation and spectral characterization,” Exp. Eye Res. 47, 71–86 (1988).
[CrossRef] [PubMed]

Eldridge, S.

L. Feeney-Burns, E. S. Hilderbrand, S. Eldridge, “Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells,” Invest. Ophthalmol. Visual Sci. 25, 195–200 (1984).

Elsner, A. E.

S. A. Burns, S. Marcos, J. S. McLellan, A. E. Elsner, “Reflectometric measurement of cone directionality and photopigment optical density,” Invest. Ophthalmol. Visual Sci. 40, S365 (1999) (ARVO Abstract No. 1935).

A. E. Elsner, S. A. Burns, E. Beausencourt, J. J. Weiter, “Foveal cone photopigment distribution: small alterations associated with macular pigment distribution,” Invest. Ophthalmol. Visual Sci. 39, 2394–2404 (1998).

A. E. Elsner, S. A. Burns, J. J. Weiter, F. C. Delori, “Infrared imaging of sub-retinal structures in the human ocular fundus,” Vision Res. 36, 191–205 (1996).
[CrossRef] [PubMed]

S. A. Burns, S. Wu, F. Delori, A. E. Elsner, “Direct measurement of human-cone-photoreceptor alignment,” J. Opt. Soc. Am. A 12, 2329–2338 (1995).
[CrossRef]

S. A. Burns, A. E. Elsner, “Color matching at high illuminances: photopigment optical density and pupil entry,” J. Opt. Soc. Am. A 10, 221–230 (1993).
[CrossRef] [PubMed]

A. E. Elsner, S. A. Burns, R. H. Webb, “Mapping cone photopigment optical density,” J. Opt. Soc. Am. A 10, 52–58 (1993).
[CrossRef] [PubMed]

Ermakov, R. W.

P. S. Bernstein, D. Y. Zhao, R. W. Ermakov, R. W. McClane, W. Gellermann, “Resonance Raman measurements of macular pigment levels in the living human retina,” Invest. Ophthalmol. Visual Sci. 40, B283 (2000) (ARVO Abstract No. 3185).

Farber, M. D.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Feeney-Burns, L.

L. Feeney-Burns, E. S. Hilderbrand, S. Eldridge, “Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells,” Invest. Ophthalmol. Visual Sci. 25, 195–200 (1984).

Fish, G. E.

W. H. Swanson, G. E. Fish, “Age-related changes in the color-match-area effect,” Vision Res. 36, 2079–2085 (1996).
[CrossRef] [PubMed]

Fishman, G. A.

P. E. Kilbride, K. R. Alexander, M. Fishman, G. A. Fishman, “Human macular pigment assessed by imaging fundus reflectometry,” Vision Res. 29, 663–674 (1989).
[CrossRef] [PubMed]

Fishman, M.

P. E. Kilbride, K. R. Alexander, M. Fishman, G. A. Fishman, “Human macular pigment assessed by imaging fundus reflectometry,” Vision Res. 29, 663–674 (1989).
[CrossRef] [PubMed]

Fitch, K. A.

J. J. Weiter, F. C. Delori, G. Wing, K. A. Fitch, “Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes,” Invest. Ophthalmol. Visual Sci. 27, 145–152 (1986).

Fitzke, F. W.

A. von Ruckmann, F. W. Fitzke, A. C. Bird, “Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope,” Invest. Ophthalmol. Visual Sci. 38, 478–486 (1997).

Fuld, K.

B. R. Hammond, K. Fuld, D. M. Snodderly, “Iris color and macular pigment optical density,” Exp. Eye Res. 62, 293–297 (1996).
[CrossRef] [PubMed]

B. R. Hammond, J. Curran-Celentano, S. Judd, K. Fuld, N. I. Krinsky, B. R. Wooten, D. M. Snodderly, “Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns,” Vision Res. 36, 2001–2012 (1996).
[CrossRef] [PubMed]

B. R. Hammond, K. Fuld, J. Curran-Celentano, “Macular pigment density in monozygotic twins,” Invest. Ophthalmol. Visual Sci. 36, 2531–2541 (1995).

B. Hammond, K. Fuld, “Interocular differences in macular pigment density,” Invest. Ophthalmol. Visual Sci. 33, 350–355 (1992).

Gabel, V.-P.

V.-P. Gabel, R. Birngruber, F. Hillenkamp, “Visible and near infrared light absorption in pigment epithelium and choroid,” in XXIII Concilium Ophthalmol Kyoto, Exerpta Medica, K. Shimuzu, J. A. Osterhuis, eds. (Oxford, Amsterdam, 1978), Vol. 14, pp. 658–662.

Gellermann, W.

P. S. Bernstein, D. Y. Zhao, R. W. Ermakov, R. W. McClane, W. Gellermann, “Resonance Raman measurements of macular pigment levels in the living human retina,” Invest. Ophthalmol. Visual Sci. 40, B283 (2000) (ARVO Abstract No. 3185).

P. S. Bernstein, M. D. Yoshida, N. B. Katz, R. W. McClane, W. Gellermann, “Raman detection of macular carotenoid pigments in intact human retina,” Invest. Ophthalmol. Visual Sci. 39, 2003–2011 (1998).

Gillbro, T.

T. Gillbro, R. J. Cogdell, “Carotenoid fluorescence,” Chem. Phys. Lett. 158, 312–316 (1989).
[CrossRef]

Goger, D. G.

F. C. Delori, D. G. Goger, B. R. Hammond, D. M. Snodderly, S. A. Burns, “Foveal lipofuscin and macular pigment,” Invest. Ophthalmol. Visual Sci. 38, S591 (1997) (ARVO Abstract No. 1657).

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

Gorrand, J. M.

Gorrand, J.-M.

J.-M. Gorrand, R. Alfieri, J.-Y. Boire, “Diffusion of the retinal layers of the living human eye,” Vision Res. 24, 1097–1106 (1984).
[CrossRef] [PubMed]

Gragoudas, E. S.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Hagstrom, S. A.

S. A. Hagstrom, J. Neitz, M. Neitz, Ratio of M/L Pigment Gene Expression Decreases with Retinal Eccentricity (Kluwer Academic, Dordrecht, The Netherlands, 1997), pp. 59–66.

Haller, J.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Hammer, M.

D. Schweitzer, M. Hammer, M. Scibor, “Imaging spectrometry in ophthalmology—principle and applications in microcirculation and in investigation of pigments,” Ophthalm. Res. 28, 37–44 (1996).
[CrossRef]

Hammond, B.

B. Hammond, K. Fuld, “Interocular differences in macular pigment density,” Invest. Ophthalmol. Visual Sci. 33, 350–355 (1992).

Hammond, B. R.

B. R. Hammond, M. Caruso-Avery, “Macular pigment optical density in a Southwestern sample,” Invest. Ophthalmol. Visual Sci. 41, 1492–1497 (2000).

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Individual variations in the spatial profile of human macular pigment,” J. Opt. Soc. Am. A 14, 1187–1196 (1997).
[CrossRef]

F. C. Delori, D. G. Goger, B. R. Hammond, D. M. Snodderly, S. A. Burns, “Foveal lipofuscin and macular pigment,” Invest. Ophthalmol. Visual Sci. 38, S591 (1997) (ARVO Abstract No. 1657).

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Density of the human crystalline lens is related to the macular pigment carotenoids, lutein and zeaxanthin,” Optom. Vision Sci. 74, 499–504 (1997).
[CrossRef]

B. R. Hammond, E. J. Johnson, R. M. Russell, N. I. Krinsky, K. J. Yeum, R. B. Edwards, D. M. Snodderly, “Dietary modification of human macular pigment density,” Invest. Ophthalmol. Visual Sci. 38, 1795–1801 (1997).

B. R. Hammond, J. Curran-Celentano, S. Judd, K. Fuld, N. I. Krinsky, B. R. Wooten, D. M. Snodderly, “Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns,” Vision Res. 36, 2001–2012 (1996).
[CrossRef] [PubMed]

B. R. Hammond, K. Fuld, D. M. Snodderly, “Iris color and macular pigment optical density,” Exp. Eye Res. 62, 293–297 (1996).
[CrossRef] [PubMed]

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Cigarette smoking and retinal carotenoids: implications for agre-related macular degeneration,” Vision Res. 36, 3003–3009 (1996).
[CrossRef] [PubMed]

B. R. Hammond, K. Fuld, J. Curran-Celentano, “Macular pigment density in monozygotic twins,” Invest. Ophthalmol. Visual Sci. 36, 2531–2541 (1995).

D. M. Snodderly, B. R. Hammond, “In vivo psychophysical assessment of nutritional and environmental influences on human ocular tissues: lens and macular pigment,” in Nutritional and Environmental Influences on Vision, A. Taylor, ed. (CRC Press, Boca Raton, Fla., 1999), pp. 251–273.

Handelman, G. J.

G. J. Handelman, E. A. Dratz, C. C. Reay, F. J. G. M. van Kuijk, “Carotenoids in the human macula and whole retina,” Invest. Ophthalmol. Visual Sci. 29, 850–855 (1988).

Henson, D.

S. Beatty, M. Boulton, D. Henson, H. H. Koh, I. J. Murray, “Macular pigment and age related macular degeneration,” Br. J. Ophthamol. 83, 867–877 (1999).
[CrossRef]

Hilderbrand, E. S.

L. Feeney-Burns, E. S. Hilderbrand, S. Eldridge, “Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells,” Invest. Ophthalmol. Visual Sci. 25, 195–200 (1984).

Hillenkamp, F.

V.-P. Gabel, R. Birngruber, F. Hillenkamp, “Visible and near infrared light absorption in pigment epithelium and choroid,” in XXIII Concilium Ophthalmol Kyoto, Exerpta Medica, K. Shimuzu, J. A. Osterhuis, eds. (Oxford, Amsterdam, 1978), Vol. 14, pp. 658–662.

Hiller, R.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Hogan, M. J.

M. J. Hogan, J. A. Alvarado, J. E. Weddell, Histology of the Human Eye (Saunders, Philadelphia, Pa., 1971).

Huang, X.-R.

R. W. Knighton, X.-R. Huang, “Directional and spectral reflectance of the rat retinal nerve fiber layer,” Invest. Ophthalmol. Visual Sci. 40, 639–647 (1999).

Itshak, F.

B. Chance, B. Schoener, R. Oshino, F. Itshak, Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples,” J. Biol. Chem. 254, 4764–4771 (1979).
[PubMed]

Joa, H.

J. T. Landrum, R. A. Bone, H. Joa, M. D. Kilburn, L. L. Moore, K. E. Sprague, “One year study of the macular pigment: the effect of 140 days of a lutein supplement,” Exp. Eye Res. 65, 57–62 (1997).
[CrossRef] [PubMed]

Johnson, E. J.

B. R. Hammond, E. J. Johnson, R. M. Russell, N. I. Krinsky, K. J. Yeum, R. B. Edwards, D. M. Snodderly, “Dietary modification of human macular pigment density,” Invest. Ophthalmol. Visual Sci. 38, 1795–1801 (1997).

Judd, S.

B. R. Hammond, J. Curran-Celentano, S. Judd, K. Fuld, N. I. Krinsky, B. R. Wooten, D. M. Snodderly, “Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns,” Vision Res. 36, 2001–2012 (1996).
[CrossRef] [PubMed]

Katz, M. L.

G. E. Eldred, M. L. Katz, “Fluorophores of the human retinal pigment epithelium: separation and spectral characterization,” Exp. Eye Res. 47, 71–86 (1988).
[CrossRef] [PubMed]

Katz, N. B.

P. S. Bernstein, M. D. Yoshida, N. B. Katz, R. W. McClane, W. Gellermann, “Raman detection of macular carotenoid pigments in intact human retina,” Invest. Ophthalmol. Visual Sci. 39, 2003–2011 (1998).

Kilbride, P. E.

P. E. Kilbride, K. R. Alexander, M. Fishman, G. A. Fishman, “Human macular pigment assessed by imaging fundus reflectometry,” Vision Res. 29, 663–674 (1989).
[CrossRef] [PubMed]

Kilburn, M. D.

J. T. Landrum, R. A. Bone, H. Joa, M. D. Kilburn, L. L. Moore, K. E. Sprague, “One year study of the macular pigment: the effect of 140 days of a lutein supplement,” Exp. Eye Res. 65, 57–62 (1997).
[CrossRef] [PubMed]

Kliegel, R.

J. S. Werner, S. K. Donnelly, R. Kliegel, “Aging and human macular pigment density,” Vision Res. 27, 257–268 (1987).
[CrossRef]

Knighton, R. W.

R. W. Knighton, X.-R. Huang, “Directional and spectral reflectance of the rat retinal nerve fiber layer,” Invest. Ophthalmol. Visual Sci. 40, 639–647 (1999).

R. W. Knighton, Q. Zhou, “The relationship between the reflectance and thickness of the retinal nerve fiber layer,” J. Glaucoma 4, 117–123 (1995).
[CrossRef] [PubMed]

Koh, H. H.

S. Beatty, M. Boulton, D. Henson, H. H. Koh, I. J. Murray, “Macular pigment and age related macular degeneration,” Br. J. Ophthamol. 83, 867–877 (1999).
[CrossRef]

Krinsky, N. I.

B. R. Hammond, E. J. Johnson, R. M. Russell, N. I. Krinsky, K. J. Yeum, R. B. Edwards, D. M. Snodderly, “Dietary modification of human macular pigment density,” Invest. Ophthalmol. Visual Sci. 38, 1795–1801 (1997).

B. R. Hammond, J. Curran-Celentano, S. Judd, K. Fuld, N. I. Krinsky, B. R. Wooten, D. M. Snodderly, “Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns,” Vision Res. 36, 2001–2012 (1996).
[CrossRef] [PubMed]

Kurzel, R. B.

R. B. Kurzel, M. L. Wolbarsht, B. S. Yamanashi, “Spectral studies on normal and cataractous intact human lenses,” Exp. Eye Res. 17, 65–71 (1973).
[CrossRef] [PubMed]

Landrum, J. T.

J. T. Landrum, R. A. Bone, H. Joa, M. D. Kilburn, L. L. Moore, K. E. Sprague, “One year study of the macular pigment: the effect of 140 days of a lutein supplement,” Exp. Eye Res. 65, 57–62 (1997).
[CrossRef] [PubMed]

R. A. Bone, J. T. Landrum, A. Cains, “Optical density spectra of the macular pigment in vivo and in vitro,” Vision Res. 32, 105–110 (1992).
[CrossRef] [PubMed]

R. A. Bone, J. T. Landrum, “Macular pigment in Henle fiber membranes: a model for Haidinger’s brushes,” Vision Res. 24, 103–108 (1984).
[CrossRef]

Lutze, M.

Marcos, S.

S. A. Burns, S. Marcos, J. S. McLellan, A. E. Elsner, “Reflectometric measurement of cone directionality and photopigment optical density,” Invest. Ophthalmol. Visual Sci. 40, S365 (1999) (ARVO Abstract No. 1935).

McClane, R. W.

P. S. Bernstein, D. Y. Zhao, R. W. Ermakov, R. W. McClane, W. Gellermann, “Resonance Raman measurements of macular pigment levels in the living human retina,” Invest. Ophthalmol. Visual Sci. 40, B283 (2000) (ARVO Abstract No. 3185).

P. S. Bernstein, M. D. Yoshida, N. B. Katz, R. W. McClane, W. Gellermann, “Raman detection of macular carotenoid pigments in intact human retina,” Invest. Ophthalmol. Visual Sci. 39, 2003–2011 (1998).

McLellan, J. S.

P. M. Prieto, S. A. Burns, J. S. McLellan, “Single pass optical density measurements by means of the lipofuscin fluorescence,” Invest. Ophthalmol. Visual Sci. 40, S429 (2000) (ARVO Abstract No. 2271-B517).

S. A. Burns, S. Marcos, J. S. McLellan, A. E. Elsner, “Reflectometric measurement of cone directionality and photopigment optical density,” Invest. Ophthalmol. Visual Sci. 40, S365 (1999) (ARVO Abstract No. 1935).

Miller, D. T.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Moore, L. L.

J. T. Landrum, R. A. Bone, H. Joa, M. D. Kilburn, L. L. Moore, K. E. Sprague, “One year study of the macular pigment: the effect of 140 days of a lutein supplement,” Exp. Eye Res. 65, 57–62 (1997).
[CrossRef] [PubMed]

Murray, I. J.

S. Beatty, M. Boulton, D. Henson, H. H. Koh, I. J. Murray, “Macular pigment and age related macular degeneration,” Br. J. Ophthamol. 83, 867–877 (1999).
[CrossRef]

Nakase, Y.

B. Chance, B. Schoener, R. Oshino, F. Itshak, Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples,” J. Biol. Chem. 254, 4764–4771 (1979).
[PubMed]

Neitz, J.

S. A. Hagstrom, J. Neitz, M. Neitz, Ratio of M/L Pigment Gene Expression Decreases with Retinal Eccentricity (Kluwer Academic, Dordrecht, The Netherlands, 1997), pp. 59–66.

Neitz, M.

S. A. Hagstrom, J. Neitz, M. Neitz, Ratio of M/L Pigment Gene Expression Decreases with Retinal Eccentricity (Kluwer Academic, Dordrecht, The Netherlands, 1997), pp. 59–66.

Nuccio, E.

P. L. Pease, A. J. Adams, E. Nuccio, “Optical density of human macular pigment,” Vision Res. 27, 705–710 (1987).
[CrossRef] [PubMed]

Oshino, R.

B. Chance, B. Schoener, R. Oshino, F. Itshak, Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples,” J. Biol. Chem. 254, 4764–4771 (1979).
[PubMed]

Pease, P. L.

P. L. Pease, A. J. Adams, E. Nuccio, “Optical density of human macular pigment,” Vision Res. 27, 705–710 (1987).
[CrossRef] [PubMed]

Peisch, R. D.

S. Y. Schmidt, R. D. Peisch, “Melanin concentration in normal human retinal pigment epithelium,” Invest. Ophthalmol. Visual Sci. 27, 1063–1067 (1986).

Pflibsen, K. P.

Pokorny, J.

J. Pokorny, V. C. Smith, M. Lutze, “Aging of the human lens,” Appl. Opt. 26, 1437–1440 (1987).
[CrossRef] [PubMed]

V. C. Smith, J. Pokorny, S. J. Starr, “Variability of color mixture data—I. Interobserver variability in the unit coordinates,” Vision Res. 16, 1087–1094 (1976).
[CrossRef]

Prieto, P. M.

P. M. Prieto, S. A. Burns, J. S. McLellan, “Single pass optical density measurements by means of the lipofuscin fluorescence,” Invest. Ophthalmol. Visual Sci. 40, S429 (2000) (ARVO Abstract No. 2271-B517).

Ramponi, P.

M. D. Boulton, F. Docchio, F. Dayhaw-Barker, P. Ramponi, R. Cubeddu, “Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium,” Vision Res. 30, 1291–1303 (1990).
[CrossRef] [PubMed]

Reay, C. C.

G. J. Handelman, E. A. Dratz, C. C. Reay, F. J. G. M. van Kuijk, “Carotenoids in the human macula and whole retina,” Invest. Ophthalmol. Visual Sci. 29, 850–855 (1988).

Russell, R. M.

B. R. Hammond, E. J. Johnson, R. M. Russell, N. I. Krinsky, K. J. Yeum, R. B. Edwards, D. M. Snodderly, “Dietary modification of human macular pigment density,” Invest. Ophthalmol. Visual Sci. 38, 1795–1801 (1997).

Schmidt, S. Y.

S. Y. Schmidt, R. D. Peisch, “Melanin concentration in normal human retinal pigment epithelium,” Invest. Ophthalmol. Visual Sci. 27, 1063–1067 (1986).

Schoener, B.

B. Chance, B. Schoener, R. Oshino, F. Itshak, Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples,” J. Biol. Chem. 254, 4764–4771 (1979).
[PubMed]

Schweitzer, D.

D. Schweitzer, M. Hammer, M. Scibor, “Imaging spectrometry in ophthalmology—principle and applications in microcirculation and in investigation of pigments,” Ophthalm. Res. 28, 37–44 (1996).
[CrossRef]

Scibor, M.

D. Schweitzer, M. Hammer, M. Scibor, “Imaging spectrometry in ophthalmology—principle and applications in microcirculation and in investigation of pigments,” Ophthalm. Res. 28, 37–44 (1996).
[CrossRef]

Seddon, J. M.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Sharpe, L. T.

A. Stockman, L. T. Sharpe, “The spectral sensitivities of the middle- and long-wavelength-sensitive cones derived from measurements in observers of known genotype,” Vision Res. 40, 1711–1737 (2000).
[CrossRef] [PubMed]

Smith, V. C.

J. Pokorny, V. C. Smith, M. Lutze, “Aging of the human lens,” Appl. Opt. 26, 1437–1440 (1987).
[CrossRef] [PubMed]

V. C. Smith, J. Pokorny, S. J. Starr, “Variability of color mixture data—I. Interobserver variability in the unit coordinates,” Vision Res. 16, 1087–1094 (1976).
[CrossRef]

Snodderly, D. M.

F. C. Delori, D. G. Goger, B. R. Hammond, D. M. Snodderly, S. A. Burns, “Foveal lipofuscin and macular pigment,” Invest. Ophthalmol. Visual Sci. 38, S591 (1997) (ARVO Abstract No. 1657).

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Individual variations in the spatial profile of human macular pigment,” J. Opt. Soc. Am. A 14, 1187–1196 (1997).
[CrossRef]

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Density of the human crystalline lens is related to the macular pigment carotenoids, lutein and zeaxanthin,” Optom. Vision Sci. 74, 499–504 (1997).
[CrossRef]

B. R. Hammond, E. J. Johnson, R. M. Russell, N. I. Krinsky, K. J. Yeum, R. B. Edwards, D. M. Snodderly, “Dietary modification of human macular pigment density,” Invest. Ophthalmol. Visual Sci. 38, 1795–1801 (1997).

B. R. Hammond, J. Curran-Celentano, S. Judd, K. Fuld, N. I. Krinsky, B. R. Wooten, D. M. Snodderly, “Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns,” Vision Res. 36, 2001–2012 (1996).
[CrossRef] [PubMed]

B. R. Hammond, K. Fuld, D. M. Snodderly, “Iris color and macular pigment optical density,” Exp. Eye Res. 62, 293–297 (1996).
[CrossRef] [PubMed]

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Cigarette smoking and retinal carotenoids: implications for agre-related macular degeneration,” Vision Res. 36, 3003–3009 (1996).
[CrossRef] [PubMed]

D. M. Snodderly, “Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins,” Am. J. Clin. Nutr. 62(supplement), 1448S–1461S (1995).
[PubMed]

D. M. Snodderly, R. S. Weinhaus, J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12, 1169–1193 (1992).
[PubMed]

D. M. Snodderly, J. D. Auran, F. C. Delori, “The macular pigment. II. Spatial distribution in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 674–684 (1984).

D. M. Snodderly, P. K. Brown, F. C. Delori, J. D. Auran, “The macular pigment. I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 660–673 (1984).

D. M. Snodderly, B. R. Hammond, “In vivo psychophysical assessment of nutritional and environmental influences on human ocular tissues: lens and macular pigment,” in Nutritional and Environmental Influences on Vision, A. Taylor, ed. (CRC Press, Boca Raton, Fla., 1999), pp. 251–273.

Sperduto, R. D.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Sprague, K. E.

J. T. Landrum, R. A. Bone, H. Joa, M. D. Kilburn, L. L. Moore, K. E. Sprague, “One year study of the macular pigment: the effect of 140 days of a lutein supplement,” Exp. Eye Res. 65, 57–62 (1997).
[CrossRef] [PubMed]

Starr, S. J.

V. C. Smith, J. Pokorny, S. J. Starr, “Variability of color mixture data—I. Interobserver variability in the unit coordinates,” Vision Res. 16, 1087–1094 (1976).
[CrossRef]

Staurenghi, G.

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

Stiles, W. S.

G. Wyszecki, W. S. Stiles, Color Science: Concepts and Methods, Quantitative Data and Formulae, 2nd ed. (Wiley, New York, 1982).

Stockman, A.

A. Stockman, L. T. Sharpe, “The spectral sensitivities of the middle- and long-wavelength-sensitive cones derived from measurements in observers of known genotype,” Vision Res. 40, 1711–1737 (2000).
[CrossRef] [PubMed]

Swanson, W. H.

W. H. Swanson, G. E. Fish, “Age-related changes in the color-match-area effect,” Vision Res. 36, 2079–2085 (1996).
[CrossRef] [PubMed]

Tiemeijer, L. F.

D. van Norren, L. F. Tiemeijer, “Spectral reflectance of the human eye,” Vision Res. 26, 313–320 (1986).
[CrossRef] [PubMed]

Ueno, N.

N. Ueno, B. Chakrabarti, “Liquefaction of human vitreous in model aphakic eyes by 300-nm UV photolysis: monitoring liquefaction by fluorescence,” Curr. Eye Res. 9, 487–492 (1990).
[CrossRef] [PubMed]

van Assendelft, O. W.

O. W. van Assendelft, Spectroscopy of Hemoglobin Derivatives (Thomas, Springfield, Ill., 1970).

van de Kraats, J.

P. J. DeLint, T. T. Berendschot, J. van de Kraats, D. van Norren, “Slow optical changes in human photoreceptors induced by light,” Invest. Ophthalmol. Visual Sci. 41, 282–289 (2000).

T. Berendschot, J. van de Kraats, D. van Norren, “Three methods to measure macular pigment compared in a lutein intake study,” Invest. Ophthalmol. Visual Sci. 39, S314 (1999) [Association for Research in Vision and Ophthalmology (ARVO) Abstract No. 1665].

J. van de Kraats, T. T. J. M. Berendschot, D. van Norren, “The pathways of light measured in fundus reflectometry,” Vision Res. 36, 2229–2247 (1996).
[CrossRef] [PubMed]

van Kuijk, F. J. G. M.

G. J. Handelman, E. A. Dratz, C. C. Reay, F. J. G. M. van Kuijk, “Carotenoids in the human macula and whole retina,” Invest. Ophthalmol. Visual Sci. 29, 850–855 (1988).

van Norren, D.

P. J. DeLint, T. T. Berendschot, J. van de Kraats, D. van Norren, “Slow optical changes in human photoreceptors induced by light,” Invest. Ophthalmol. Visual Sci. 41, 282–289 (2000).

T. Berendschot, J. van de Kraats, D. van Norren, “Three methods to measure macular pigment compared in a lutein intake study,” Invest. Ophthalmol. Visual Sci. 39, S314 (1999) [Association for Research in Vision and Ophthalmology (ARVO) Abstract No. 1665].

P. J. Delint, T. Berendschot, D. van Norren, “Local photoreceptor alignment measured with a scanning laser ophthalmoscope,” Vision Res. 37, 243–248 (1997).
[CrossRef] [PubMed]

J. van de Kraats, T. T. J. M. Berendschot, D. van Norren, “The pathways of light measured in fundus reflectometry,” Vision Res. 36, 2229–2247 (1996).
[CrossRef] [PubMed]

D. van Norren, L. F. Tiemeijer, “Spectral reflectance of the human eye,” Vision Res. 26, 313–320 (1986).
[CrossRef] [PubMed]

D. van Norren, personal communication (Human Factors Research Institute, P.O. Box 23, Soesterberg, 3769ZG, The Netherlands, 1999).

von Ruckmann, A.

A. von Ruckmann, F. W. Fitzke, A. C. Bird, “Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope,” Invest. Ophthalmol. Visual Sci. 38, 478–486 (1997).

Webb, R. H.

Weddell, J. E.

M. J. Hogan, J. A. Alvarado, J. E. Weddell, Histology of the Human Eye (Saunders, Philadelphia, Pa., 1971).

Weinhaus, R. S.

D. M. Snodderly, R. S. Weinhaus, J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12, 1169–1193 (1992).
[PubMed]

Weiter, J. J.

A. E. Elsner, S. A. Burns, E. Beausencourt, J. J. Weiter, “Foveal cone photopigment distribution: small alterations associated with macular pigment distribution,” Invest. Ophthalmol. Visual Sci. 39, 2394–2404 (1998).

A. E. Elsner, S. A. Burns, J. J. Weiter, F. C. Delori, “Infrared imaging of sub-retinal structures in the human ocular fundus,” Vision Res. 36, 191–205 (1996).
[CrossRef] [PubMed]

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

J. J. Weiter, F. C. Delori, G. Wing, K. A. Fitch, “Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes,” Invest. Ophthalmol. Visual Sci. 27, 145–152 (1986).

Werner, J. S.

J. S. Werner, S. K. Donnelly, R. Kliegel, “Aging and human macular pigment density,” Vision Res. 27, 257–268 (1987).
[CrossRef]

J. S. Werner, B. R. Wooten, “Opponent chromatic mechanisms: relation to photopigments and hue naming,” J. Opt. Soc. Am. 69, 422–434 (1979).
[CrossRef] [PubMed]

Willett, W.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Willmer, E. N.

G. S. Brindley, E. N. Willmer, “The reflection of light from the macular and peripheral fundus oculi in man,” J. Physiol. (London) 116, 350–356 (1952).

Wing, G.

J. J. Weiter, F. C. Delori, G. Wing, K. A. Fitch, “Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes,” Invest. Ophthalmol. Visual Sci. 27, 145–152 (1986).

Wolbarsht, M. L.

R. B. Kurzel, M. L. Wolbarsht, B. S. Yamanashi, “Spectral studies on normal and cataractous intact human lenses,” Exp. Eye Res. 17, 65–71 (1973).
[CrossRef] [PubMed]

Wooten, B. R.

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Density of the human crystalline lens is related to the macular pigment carotenoids, lutein and zeaxanthin,” Optom. Vision Sci. 74, 499–504 (1997).
[CrossRef]

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Individual variations in the spatial profile of human macular pigment,” J. Opt. Soc. Am. A 14, 1187–1196 (1997).
[CrossRef]

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Cigarette smoking and retinal carotenoids: implications for agre-related macular degeneration,” Vision Res. 36, 3003–3009 (1996).
[CrossRef] [PubMed]

B. R. Hammond, J. Curran-Celentano, S. Judd, K. Fuld, N. I. Krinsky, B. R. Wooten, D. M. Snodderly, “Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns,” Vision Res. 36, 2001–2012 (1996).
[CrossRef] [PubMed]

J. S. Werner, B. R. Wooten, “Opponent chromatic mechanisms: relation to photopigments and hue naming,” J. Opt. Soc. Am. 69, 422–434 (1979).
[CrossRef] [PubMed]

Wu, S.

Wyszecki, G.

G. Wyszecki, W. S. Stiles, Color Science: Concepts and Methods, Quantitative Data and Formulae, 2nd ed. (Wiley, New York, 1982).

Yamanashi, B. S.

R. B. Kurzel, M. L. Wolbarsht, B. S. Yamanashi, “Spectral studies on normal and cataractous intact human lenses,” Exp. Eye Res. 17, 65–71 (1973).
[CrossRef] [PubMed]

Yannuzzi, L. A.

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

Yeum, K. J.

B. R. Hammond, E. J. Johnson, R. M. Russell, N. I. Krinsky, K. J. Yeum, R. B. Edwards, D. M. Snodderly, “Dietary modification of human macular pigment density,” Invest. Ophthalmol. Visual Sci. 38, 1795–1801 (1997).

Yoshida, M. D.

P. S. Bernstein, M. D. Yoshida, N. B. Katz, R. W. McClane, W. Gellermann, “Raman detection of macular carotenoid pigments in intact human retina,” Invest. Ophthalmol. Visual Sci. 39, 2003–2011 (1998).

Zhao, D. Y.

P. S. Bernstein, D. Y. Zhao, R. W. Ermakov, R. W. McClane, W. Gellermann, “Resonance Raman measurements of macular pigment levels in the living human retina,” Invest. Ophthalmol. Visual Sci. 40, B283 (2000) (ARVO Abstract No. 3185).

Zhou, Q.

R. W. Knighton, Q. Zhou, “The relationship between the reflectance and thickness of the retinal nerve fiber layer,” J. Glaucoma 4, 117–123 (1995).
[CrossRef] [PubMed]

Am. J. Clin. Nutr. (1)

D. M. Snodderly, “Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins,” Am. J. Clin. Nutr. 62(supplement), 1448S–1461S (1995).
[PubMed]

Appl. Opt. (3)

Br. J. Ophthamol. (1)

S. Beatty, M. Boulton, D. Henson, H. H. Koh, I. J. Murray, “Macular pigment and age related macular degeneration,” Br. J. Ophthamol. 83, 867–877 (1999).
[CrossRef]

Chem. Phys. Lett. (1)

T. Gillbro, R. J. Cogdell, “Carotenoid fluorescence,” Chem. Phys. Lett. 158, 312–316 (1989).
[CrossRef]

Curr. Eye Res. (1)

N. Ueno, B. Chakrabarti, “Liquefaction of human vitreous in model aphakic eyes by 300-nm UV photolysis: monitoring liquefaction by fluorescence,” Curr. Eye Res. 9, 487–492 (1990).
[CrossRef] [PubMed]

Exp. Eye Res. (4)

R. B. Kurzel, M. L. Wolbarsht, B. S. Yamanashi, “Spectral studies on normal and cataractous intact human lenses,” Exp. Eye Res. 17, 65–71 (1973).
[CrossRef] [PubMed]

G. E. Eldred, M. L. Katz, “Fluorophores of the human retinal pigment epithelium: separation and spectral characterization,” Exp. Eye Res. 47, 71–86 (1988).
[CrossRef] [PubMed]

J. T. Landrum, R. A. Bone, H. Joa, M. D. Kilburn, L. L. Moore, K. E. Sprague, “One year study of the macular pigment: the effect of 140 days of a lutein supplement,” Exp. Eye Res. 65, 57–62 (1997).
[CrossRef] [PubMed]

B. R. Hammond, K. Fuld, D. M. Snodderly, “Iris color and macular pigment optical density,” Exp. Eye Res. 62, 293–297 (1996).
[CrossRef] [PubMed]

Invest. Ophthalmol. Visual Sci. (21)

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

P. S. Bernstein, M. D. Yoshida, N. B. Katz, R. W. McClane, W. Gellermann, “Raman detection of macular carotenoid pigments in intact human retina,” Invest. Ophthalmol. Visual Sci. 39, 2003–2011 (1998).

P. S. Bernstein, D. Y. Zhao, R. W. Ermakov, R. W. McClane, W. Gellermann, “Resonance Raman measurements of macular pigment levels in the living human retina,” Invest. Ophthalmol. Visual Sci. 40, B283 (2000) (ARVO Abstract No. 3185).

A. E. Elsner, S. A. Burns, E. Beausencourt, J. J. Weiter, “Foveal cone photopigment distribution: small alterations associated with macular pigment distribution,” Invest. Ophthalmol. Visual Sci. 39, 2394–2404 (1998).

B. R. Hammond, M. Caruso-Avery, “Macular pigment optical density in a Southwestern sample,” Invest. Ophthalmol. Visual Sci. 41, 1492–1497 (2000).

T. Berendschot, J. van de Kraats, D. van Norren, “Three methods to measure macular pigment compared in a lutein intake study,” Invest. Ophthalmol. Visual Sci. 39, S314 (1999) [Association for Research in Vision and Ophthalmology (ARVO) Abstract No. 1665].

B. Hammond, K. Fuld, “Interocular differences in macular pigment density,” Invest. Ophthalmol. Visual Sci. 33, 350–355 (1992).

B. R. Hammond, K. Fuld, J. Curran-Celentano, “Macular pigment density in monozygotic twins,” Invest. Ophthalmol. Visual Sci. 36, 2531–2541 (1995).

D. M. Snodderly, J. D. Auran, F. C. Delori, “The macular pigment. II. Spatial distribution in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 674–684 (1984).

D. M. Snodderly, P. K. Brown, F. C. Delori, J. D. Auran, “The macular pigment. I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas,” Invest. Ophthalmol. Visual Sci. 25, 660–673 (1984).

B. R. Hammond, E. J. Johnson, R. M. Russell, N. I. Krinsky, K. J. Yeum, R. B. Edwards, D. M. Snodderly, “Dietary modification of human macular pigment density,” Invest. Ophthalmol. Visual Sci. 38, 1795–1801 (1997).

G. J. Handelman, E. A. Dratz, C. C. Reay, F. J. G. M. van Kuijk, “Carotenoids in the human macula and whole retina,” Invest. Ophthalmol. Visual Sci. 29, 850–855 (1988).

L. Feeney-Burns, E. S. Hilderbrand, S. Eldridge, “Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells,” Invest. Ophthalmol. Visual Sci. 25, 195–200 (1984).

J. J. Weiter, F. C. Delori, G. Wing, K. A. Fitch, “Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes,” Invest. Ophthalmol. Visual Sci. 27, 145–152 (1986).

S. Y. Schmidt, R. D. Peisch, “Melanin concentration in normal human retinal pigment epithelium,” Invest. Ophthalmol. Visual Sci. 27, 1063–1067 (1986).

A. von Ruckmann, F. W. Fitzke, A. C. Bird, “Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope,” Invest. Ophthalmol. Visual Sci. 38, 478–486 (1997).

S. A. Burns, S. Marcos, J. S. McLellan, A. E. Elsner, “Reflectometric measurement of cone directionality and photopigment optical density,” Invest. Ophthalmol. Visual Sci. 40, S365 (1999) (ARVO Abstract No. 1935).

P. J. DeLint, T. T. Berendschot, J. van de Kraats, D. van Norren, “Slow optical changes in human photoreceptors induced by light,” Invest. Ophthalmol. Visual Sci. 41, 282–289 (2000).

P. M. Prieto, S. A. Burns, J. S. McLellan, “Single pass optical density measurements by means of the lipofuscin fluorescence,” Invest. Ophthalmol. Visual Sci. 40, S429 (2000) (ARVO Abstract No. 2271-B517).

R. W. Knighton, X.-R. Huang, “Directional and spectral reflectance of the rat retinal nerve fiber layer,” Invest. Ophthalmol. Visual Sci. 40, 639–647 (1999).

F. C. Delori, D. G. Goger, B. R. Hammond, D. M. Snodderly, S. A. Burns, “Foveal lipofuscin and macular pigment,” Invest. Ophthalmol. Visual Sci. 38, S591 (1997) (ARVO Abstract No. 1657).

J. Am. Med. Assoc. (1)

J. M. Seddon, U. A. Ajani, R. D. Sperduto, R. Hiller, N. Blair, T. C. Burton, M. D. Farber, E. S. Gragoudas, J. Haller, D. T. Miller, L. A. Yannuzzi, W. Willett, “Dietary carotenoids, vitamins A, C, and E and advanced age-related macular degeneration,” J. Am. Med. Assoc. 272, 1413–1420 (1994).
[CrossRef]

J. Biol. Chem. (1)

B. Chance, B. Schoener, R. Oshino, F. Itshak, Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples,” J. Biol. Chem. 254, 4764–4771 (1979).
[PubMed]

J. Glaucoma (1)

R. W. Knighton, Q. Zhou, “The relationship between the reflectance and thickness of the retinal nerve fiber layer,” J. Glaucoma 4, 117–123 (1995).
[CrossRef] [PubMed]

J. Neurosci. (1)

D. M. Snodderly, R. S. Weinhaus, J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12, 1169–1193 (1992).
[PubMed]

J. Opt. Soc. Am. (1)

J. Opt. Soc. Am. A (6)

J. Physiol. (London) (1)

G. S. Brindley, E. N. Willmer, “The reflection of light from the macular and peripheral fundus oculi in man,” J. Physiol. (London) 116, 350–356 (1952).

Ophthalm. Res. (1)

D. Schweitzer, M. Hammer, M. Scibor, “Imaging spectrometry in ophthalmology—principle and applications in microcirculation and in investigation of pigments,” Ophthalm. Res. 28, 37–44 (1996).
[CrossRef]

Optom. Vision Sci. (1)

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Density of the human crystalline lens is related to the macular pigment carotenoids, lutein and zeaxanthin,” Optom. Vision Sci. 74, 499–504 (1997).
[CrossRef]

Vision Res. (16)

J. van de Kraats, T. T. J. M. Berendschot, D. van Norren, “The pathways of light measured in fundus reflectometry,” Vision Res. 36, 2229–2247 (1996).
[CrossRef] [PubMed]

P. E. Kilbride, K. R. Alexander, M. Fishman, G. A. Fishman, “Human macular pigment assessed by imaging fundus reflectometry,” Vision Res. 29, 663–674 (1989).
[CrossRef] [PubMed]

J. S. Werner, S. K. Donnelly, R. Kliegel, “Aging and human macular pigment density,” Vision Res. 27, 257–268 (1987).
[CrossRef]

P. L. Pease, A. J. Adams, E. Nuccio, “Optical density of human macular pigment,” Vision Res. 27, 705–710 (1987).
[CrossRef] [PubMed]

R. A. Bone, J. T. Landrum, A. Cains, “Optical density spectra of the macular pigment in vivo and in vitro,” Vision Res. 32, 105–110 (1992).
[CrossRef] [PubMed]

D. van Norren, L. F. Tiemeijer, “Spectral reflectance of the human eye,” Vision Res. 26, 313–320 (1986).
[CrossRef] [PubMed]

B. R. Hammond, B. R. Wooten, D. M. Snodderly, “Cigarette smoking and retinal carotenoids: implications for agre-related macular degeneration,” Vision Res. 36, 3003–3009 (1996).
[CrossRef] [PubMed]

B. R. Hammond, J. Curran-Celentano, S. Judd, K. Fuld, N. I. Krinsky, B. R. Wooten, D. M. Snodderly, “Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns,” Vision Res. 36, 2001–2012 (1996).
[CrossRef] [PubMed]

V. C. Smith, J. Pokorny, S. J. Starr, “Variability of color mixture data—I. Interobserver variability in the unit coordinates,” Vision Res. 16, 1087–1094 (1976).
[CrossRef]

M. D. Boulton, F. Docchio, F. Dayhaw-Barker, P. Ramponi, R. Cubeddu, “Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium,” Vision Res. 30, 1291–1303 (1990).
[CrossRef] [PubMed]

A. E. Elsner, S. A. Burns, J. J. Weiter, F. C. Delori, “Infrared imaging of sub-retinal structures in the human ocular fundus,” Vision Res. 36, 191–205 (1996).
[CrossRef] [PubMed]

A. Stockman, L. T. Sharpe, “The spectral sensitivities of the middle- and long-wavelength-sensitive cones derived from measurements in observers of known genotype,” Vision Res. 40, 1711–1737 (2000).
[CrossRef] [PubMed]

P. J. Delint, T. Berendschot, D. van Norren, “Local photoreceptor alignment measured with a scanning laser ophthalmoscope,” Vision Res. 37, 243–248 (1997).
[CrossRef] [PubMed]

W. H. Swanson, G. E. Fish, “Age-related changes in the color-match-area effect,” Vision Res. 36, 2079–2085 (1996).
[CrossRef] [PubMed]

J.-M. Gorrand, R. Alfieri, J.-Y. Boire, “Diffusion of the retinal layers of the living human eye,” Vision Res. 24, 1097–1106 (1984).
[CrossRef] [PubMed]

R. A. Bone, J. T. Landrum, “Macular pigment in Henle fiber membranes: a model for Haidinger’s brushes,” Vision Res. 24, 103–108 (1984).
[CrossRef]

Other (25)

M. J. Hogan, J. A. Alvarado, J. E. Weddell, Histology of the Human Eye (Saunders, Philadelphia, Pa., 1971).

Direct measurements74of the ILM reflectance ρ used a perfect mirror as reference (with curvature equal to that found in the eye). To convert this reflectance into an equivalent reflectance (reference: perfect diffuser),34we used Eqs. (27) and (28) of Gorrand and Delori’s paper.74The equivalent reflectance of the ILM is then RILM=(πρr2)/(4A),where the reflectance is ρ=0041 %±0.0019 %(seven young subjects), ris the radius of curvature of the foveal depression (r=1.22±0.22 mm),and A is the area of the retinal test field (0.26 mm2for a 2°-diameter field). Using the original data (n=7, ages: 16–26 years), we found that RILM=0.019 %±0.013 % (range: 0.007%–0.04%).

Crystalline lens AF was measured in three study subjects (ages: 37, 46, and 57 years) by focusing the sampling volume within the lens (using an additional ophthalmic lens). Excitation spectra decreased by 76%±3%between 470 and 550 nm. Emission spectra were maximal at 520±5 nmfor Λ=470 nmand decreased to 10% of that maximum fluorescence at 655±8 nm. Fluorescence intensity increased with age of the three subjects.

By rewriting relation (20) for two-emission wavelengths, λ=620 nmand λ=λdet,and assuming that Sais small compared with the foveal fluorescence and that its emission decreases exponentially, we can show that ΔD∝Sa(470, 620){1-[FF′(470, 620)/FF′(470, λdet)]exp[-α(λdet-620)]}.The measure ΔDis then proportional to Saand increases in a quasi-exponential manner with increasing λdettoward the true value (as sketched in the top of Fig. 10). By performing detailed fits for a number of subjects, we estimated that the amount of underestimation is approximately 1/3 of ΔD.

Reflectances Raare positively correlated with age (r=0.4,p<0.0001) as a direct result of the increase with age of media-corrected reflectances RF′(470).This increase in reflectance cannot be accounted for by known age-related retinal changes. As we mentioned before,35we believe that this increase may result from a slight overestimation of our media correction method.

The foveal fluorescence FF′in relation (21) was expressed as a function of the reflectance RF*of layers posterior to the MP [as in Eq. (6)] by RF′(λ)=Ra(λ)+RF*(λ)10-2Kmp(λ)DAF,c(460).The parameter Ra/RF*is then the single free parameter in the fits.

D. van Norren, personal communication (Human Factors Research Institute, P.O. Box 23, Soesterberg, 3769ZG, The Netherlands, 1999).

Ex vivo measurements in sections of RPE showed that lipofuscin fluorescence at the fovea was 81%±14%of that at the perifovea.55 This ratio was calculated from the fluorescence measurements in sections of the RPE (bleached melanin) and from RPE cell heights at both sites. In vivo fluorescence at the fovea, measured with Λ=550 nm(no MP absorption), was on average 64%±10% of that at the perifovea. If we assume that the difference between these ratios results from a higher apical melanin absorption at the fovea, then we can calculate that the melanin density difference is log(64/81)/[Kme(550)+Kme(710)]or 0.14±0.14 D.U.at 460 nm.

V.-P. Gabel, R. Birngruber, F. Hillenkamp, “Visible and near infrared light absorption in pigment epithelium and choroid,” in XXIII Concilium Ophthalmol Kyoto, Exerpta Medica, K. Shimuzu, J. A. Osterhuis, eds. (Oxford, Amsterdam, 1978), Vol. 14, pp. 658–662.

O. W. van Assendelft, Spectroscopy of Hemoglobin Derivatives (Thomas, Springfield, Ill., 1970).

Ex vivo data from the paper of Weiter et al.55for RPE melanin was multiplied by 2.2 to account for the fact that melanin transmission in that study was measured in the 500–600-nm spectral range and is expressed here at 460 nm. Mean melanin densities at 460 nm for single pass through the RPE were computed as 0.56±0.19and 0.31±0.10 D.U.for the fovea and for sites at 6°–7° on either side of the fovea, respectively. Mean density difference in melanin between both sites was 0.25±0.15 D.U.

F. C. Delori, “RPE lipofuscin in aging and age related macular degeneration,” in Retinal Pigment Epithelium and Macular Diseases, F. C. Piccolino, G. Coscas, eds. (Kluwer Academic, Dordrecht, The Netherlands, 1998), pp. 37–45.

S. A. Hagstrom, J. Neitz, M. Neitz, Ratio of M/L Pigment Gene Expression Decreases with Retinal Eccentricity (Kluwer Academic, Dordrecht, The Netherlands, 1997), pp. 59–66.

Fluorescence F′and reflectance R′incorporate absolute corrections to account for ocular media absorption. This combines our individually determined lens densities, which are relative to the density of a 44-year-old average observer,35 and mean lens densities at age 44 years from Pokorny et al.67 Average media-corrected fluorescences F′ and reflectances R′ at the fovea (F) and at the perifovea (P) were (n=159)At F:  FF′(470, 710)=81±44 AFUFF′(550, 710)=136±62 AFUAt P:  FP′(470, 710)=310±129 AFUFP′(550, 710)=214±91 AFUAt F:  RF′(470)=0.61%±0.26%RF′(550)=1.66%±0.61%At P:  RP′(470)=2.74%±0.89%RP′(550)=3.10%±0.91% The AF unit AFU is nJ nm-1 sr-1/J.

We assume that the MP distribution D(r)is exponential12,17and that it is given by D(r)=D(0)10-2 log(2)(r/FWHM),where r is the distance to the center. To convert DHFPestimated with a 0.8°-diameter field to equivalent values for a 2° test field, we further assumed that the peak density D(0)and the full width at half-maximum (FWHM) were linked by the experimentally derived relation D(0)=0.13+0.22FWHM.17 Using various values of FWHM, we obtained a nonlinear relationship between the densities for the 2°- and the 0.8°-diameter field: D2=-0.03+0.31D0.8+1.14D0.82(for D0.8<0.8 D.U.). Tp predict the densities DAFmeasured by the AF method (test field of radius R), we calculate DAF=log∑0RA(r)P(r)rΔr-log∑0RA(r)P(r)10-D(r)rΔr, where P(r)is the distribution of fundus AF in the absence of MP and A(r)is the product of the distribution of retinal irradiance and sensitivity of the fluorometer. Densities DAFwere computed with a constant P(r),the measured distribution A(r),37and an increment of r=0.005°.

Most older subjects in this study and subjects in the study of Hammond et al.16were recruited from the Harvard Cooperative Program on Aging (Roslindale, Mass.), an organization devoted to good health through research and education.

An error in DAF(460)occurs if the excitation spectrum of tissues posterior to the MP at the fovea is not proportional to that at the perifovea. We model this; we equate foveal fluorescence as FF*(Λ, λ)=kFP*(Λ, λ)+Δ(Λ, λ),where FF*and FP*are the fluorescences at the fovea and at the perifovea, respectively, k is a constant, and Δ accounts for the spectral difference between the fovea and the perifovea (can be negative). Substitution of FF*in Eq. (4) and derivation of Eq. (5), assuming that Δ/FP*≪1,gives the following approximation for the measured density: DAF′(460)≈DAF(460)+k log(e)Kmp(Λ1)-Kmp(Λ2)×Δ(Λ1, λ)FP*(Λ1, λ)-Δ(Λ2, λ)FP*(Λ2, λ).If the foveal excitation spectrum is shifted toward shorter wavelengths, then Δ decreases with increasing Λ (positive to negative), and the term in square brackets >0, resulting in an overestimation of the MP density. The opposite will occur if the shift is toward longer wavelengths.

Equivalent reflectances of the fundus use a perfect Lambertian reflector located at the retina of an artificial eye as reference.21,22

For a subset of the population, we performed the fluorescence measurements at the peripheral site twice in the following order: excitations at 550, 510, 470, 430, 550, 510, and 470 nm. Rods were bleached only by the illumination and focusing lights before the first 550-nm exposure, whereas they were fully bleached (≈98%) by four excitation exposures before the second 550-nm exposure. For 30 subjects, the fluorescence at the second 550-nm exposure was 1.023±0.035times higher than that at the first exposure (p=0.001).This corresponds to a single-pass rod density of 0.02±0.03 D.U.at 500 nm. Thus approximately 60%–80% of the rods were bleached by the illumination and focusing lights (assuming a single-pass rod density of 0.05–0.1 D.U. at 500 nm).

The distribution of retinal irradiance and sensitivity of the fluorometer in the 2° test field was measured optically by displacing a small reflecting surface (equivalent to ≈0.2° diameter) in a focal plane located in front of the instrument. The product of both distributions at different radii was 1.00, 1.00, 0.90, 0.80, and 0.20 at 0°, 0.25°, 0.50°, 0.75°, and 1.00°, respectively.

The conversion factor used in this study was slightly larger than that calculated by using Eq. (10) from other MP spectra cited in the literature. A difference was found of 1% for the spectrum of a mixture of liposome-bound lutein and zeaxanthin in Bone et al.,4of 5% for the psychophysically determined spectrum in Wyszecki and Stiles,5and of 6% for the spectrum in fixed primate retinas obtained by microspectrometry in Snodderly et al.3

F. C. Delori, “Macular pigment density measured by reflectometry and fluorophotometry,” in Opthalmic and Visual Optics and Noninvasive Assessment of the Visual System, Vol. 3 of 1993 OSA Technical Digest Series (Optical Society of America, Washington D.C., 1993), pp. 240–243.

D. M. Snodderly, B. R. Hammond, “In vivo psychophysical assessment of nutritional and environmental influences on human ocular tissues: lens and macular pigment,” in Nutritional and Environmental Influences on Vision, A. Taylor, ed. (CRC Press, Boca Raton, Fla., 1999), pp. 251–273.

G. Wyszecki, W. S. Stiles, Color Science: Concepts and Methods, Quantitative Data and Formulae, 2nd ed. (Wiley, New York, 1982).

The late Dr. Paul Brown measured an absorption spectrum of MP on a fresh retinal tissue (macaqua mulata) by using microspectrophotometry (Fig. 4, central panel, in Ref. 3). The normalized absorption data are (in steps of 5 nm) 0.451 (400 nm), 0.501, 0.553, 0.605, 0.682, 0.757, 0.811, 0.844, 0.863, 0.904, 0.960, 1.000 (455 nm), 0.983, 0.923, 0.838, 0.788, 0.777, 0.763, 0.732, 0.663, 0.555 (500 nm), 0.428, 0.303, 0.196, 0.116, 0.067, 0.041, 0.026, 0.017, 0.010, and 0.005 (550 nm).

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Figures (12)

Fig. 1
Fig. 1

(top) Schematic diagram (top) representing a section through the retina at the fovea, where the outward displacement of retinal cells causes a thinning of the retina. The symbols are PhR, photoreceptors; ILM, inner limiting membrane of the retina; RPE, retinal pigmented epithelium (containing both the fluorophore lipofuscin and the absorber melanin), and BM, Bruch’s membrane. The choroid is rich in blood and provides nutrients for the photoreceptors. The blue-absorbing macular pigment (MP) is located in the cone axons at the center of the fovea. (bottom) Absorption spectrum of MP (thick curve) measured by Brown6 and normalized to its peak absorption at 455 nm. The thin curve is the same spectrum averaged over the excitation spectral band by using Eq. (10).

Fig. 2
Fig. 2

(top) Fluorescence excitation (measured at 710 nm) and emission spectra (for 470- and 550-nm excitation) measured at the fovea (F) and at 7° temporal to the fovea (P) in a 56-year-old male subject. Fluorescence was measured with a circular test area of 585 µm (2°) in diameter. Fluorescence is expressed in nJ nm-1 sr-1/J. Excitation spectra represent the fluorescence intensity at 710 nm as a function of the excitation wavelength (430, 470, 510, and 550 nm); to avoid confusion, only the emission spectra for 470- and 550-nm excitation are shown. (bottom) Log-ratio spectrum of perifoveal to foveal fluorescence (solid circles) and fitted MP spectrum (gray curve). The vertical arrow represents the term in the square brackets in Eq. (5), and this quantity is proportional to the MP density.

Fig. 3
Fig. 3

(top) Reflectance spectra measured at the fovea (F) and at 7° temporal to the fovea (P) in the same subject as that in Fig. 1. Reflectance was measured in a circular test area of 585 µm (2°) in diameter. (bottom) Log-ratio spectrum of the perifoveal to foveal reflectance (black curve) and fitted MP spectrum (gray curve); the gray arrows correspond to the term in the square brackets in Eq. (9), which is a quantity proportional to the MP density. The two black arrows near 550 nm highlight the decrease of the log ratio with wavelength, which is associated with differential melanin absorption between the fovea and the peripheral site (Subsection 5.D).

Fig. 4
Fig. 4

MP densities determined by the AF method (DAF) for normal subjects as a function of age (n=159). The test field was 2° in diameter.

Fig. 5
Fig. 5

(top) MP densities determined by the reflectance method (DRE) as a function of age. The subjects are the same as those in Fig. 4. The test field was 2° in diameter. (bottom) DRE as a function of the MP densities determined by the fluorescence method (DAF). The dashed line represents equality of the two estimates, and the solid line is the linear regression DRE=0.086+0.30DAF (r2=0.54, p<0.0001). The 95% confidence intervals were 0.06 and 0.11 D.U. for the intercept and 0.25 and 0.34 for the slope.

Fig. 6
Fig. 6

Variation of the measured log ratio (symbols) and the fitted MP spectra (curves) for both the AF method (left) and the RE method (right). The spectra are for the same seven subjects (ages given to the left of each spectrum). The derived MP densities (DAF and DRE for the AF and RE methods, respectively) are given on the right of each spectrum together with the regression’s r2 (in parentheses). The data for two subjects (ages: 62 and 45 years) were measured twice, and the fits made on the averaged data (error bars: SD). The log ratios for the AF method were measured at 710 nm with Λ=430, 470, 510, and 550 nm (as for all subjects in this study). Additionally, we used Λ=450, 490, and 530 nm in two subjects. The log-ratio fits for the RE method were made by using λ=430, 450, 470, 490, 520, and 550 nm (solid symbols). Two additional wavelengths, λ=540 and 575 nm, were used in the determination of RPE melanin (open symbols; Subsection 5.D). The three lowest spectra in each panel (ages: 63, 45, and 30 years) correspond to the three subjects for which the MP density estimates by the HFP method were less than 0.05 D.U. (see Fig. 7); the MP spectral signature is seen on the AF and RE log-ratio spectra.

Fig. 7
Fig. 7

Comparison of MP densities measured in 30 subjects by the fluorescence method (DAF, top) and the reflectance method (DRE, bottom) with MP densities measured by HFP (DHFP). Test fields were 2.0° and 0.8° in diameter for the optical and psychophysical methods, respectively. Plots were displaced to avoid overlap. Symbols with a central dot correspond to subjects in which contralateral eyes were tested. The black dashed lines at 45° are lines of equal density for both methods, and solid lines are regression lines. The regression line for the AF method was DAF=0.26+0.58DHFP (r2=0.60, p<0.0001). The 95% confidence intervals were 0.18 and 0.35 D.U. for the intercept and 0.40 and 0.77 for the slope. The regression line for the RE method was DRE=0.16+0.15DHFP (r2=0.38, p=0.0003). The 95% confidence intervals were 0.12 and 0.19 D.U. for the intercept and 0.08 and 0.23 for the slope. The two thick, gray dashed lines are the regression lines after adjusting for differences in test field diameter.

Fig. 8
Fig. 8

Relationship between the density distribution of the MP and MP density estimated by the AF method (2°) and by HFP (0.8° and 2°). Different densities simulating different techniques were computed for an exponential distribution of MP.43 The FWHM is 2°, similar to the mean width observed in vivo.17 Flicker photometry (DHFP) estimates the density at the edge of the test stimulus, whereas the AF method (DAF) provides an average density over the test field. For equal test field size, AF estimates are thus higher than HFP measures.

Fig. 9
Fig. 9

Difference in the amount of RPE melanin at the fovea and at the perifovea as a function of age. The melanin density difference ndme(460) was derived by fitting Eq. (17) to the log-ratio reflectance data. Regression line: ndme(460)=0.12-0.0003×(age) with r2=0.001 (p=0.7). More melanin was sampled at the perifovea than at the fovea in 14 out of 147 subjects (negative values).

Fig. 10
Fig. 10

Effect of an anterior fluorophore on the MP density estimates DAF by the AF method. (top) Average MP densities determined with the AF method (Λ=470 and 550 nm) as a function of the wavelengths λdet at which AF is measured. Mean densities are given for three age groups. Dashed lines are extrapolations that tend toward the average correct MP densities in each group. The AF method uses 710 nm as the detecting wavelength, resulting in a slight underestimation in MP density. The density difference ΔD between the densities measured with λdet=710 nm and λdet=620 nm is a measure of the magnitude of the secondary fluorescence.72 This measure decreases significantly with age (p<0.0001). (top inset) Schematic representation of the emission spectrum of lipofuscin (LF), of a secondary fluorophore (Sa), and of the combined fluorophores (LF+Sa). (bottom) Density difference ΔD as a function of the measured foveal fluorescence (Λ=470 nm).

Fig. 11
Fig. 11

Effect of an anterior reflector/scatterer on the MP densities estimated by the RE method. The MP density DRE,c derived from the RE method is given as a function of the MP densities DAF,c derived from the AF method. This plot is similar to that at the bottom of Fig. 5, except that both densities were corrected to account for the effect of RPE melanin. The curves are fits of relation (21) to the data,78 assuming that the anterior reflector is spectrally neutral (curve A) or that the reflectance Ra decreases sharply [Ra(550)=0] with increasing wavelength (curve B). The fitted parameters Ra(470)/RF*(470) were 0.38 and 0.25 for curves A and B, respectively. The corresponding reflectances Ra(470) were, respectively, 0.39% and 0.33%, similar to the mean reflectances found with Eq. (22).

Fig. 12
Fig. 12

Comparison of MP densities DAF estimated by the AF method and densities DHFP estimated by the HFP method (both with a 2°-diameter test field). In these data, we accounted for field size differences (Subsection 4.F) and for those effects that were identified in Section 5 (self-screening of visual pigment, RPE melanin, retinal capillaries, and secondary fluorophore). The open circles are the corrected data. The lightly shaded area represents the 95% confidence interval of the linear regression of DAF on DHFP (n=30, intercept ≈0.23, and slope ≈0.62). The three jagged lines illustrate the different density corrections; starting from the open square (original data of Fig. 7), we implement the corrections for field size scaling (left), for RPE melanin and blood (down), for self-screening of visual pigment (right, 0.05 D.U.), and for the secondary fluorophore (up). The darkly shaded area represents the range of predictions for DAF and DHFP based on the difference in sampling criteria used in both methods (Subsection 5.A).43

Tables (2)

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Table 2 Macular Pigment Density by the Autofluorescence and Reflectance Methods

Equations (39)

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FF(Λ, λ)=FF*(Λ, λ)10-DF(Λ)-DF(λ),
FP(Λ, λ)=FP*(Λ, λ)10-DP(Λ)-DP(λ).
logFP(Λ, λ)FF(Λ, λ)=logFP*(Λ, λ)FF*(Λ, λ)+[DF(Λ)-DP(Λ)]+[DF(λ)-DP(λ)].
logFP(Λ, λ)FF(Λ, λ)=logFP*(Λ, λ)FF*(Λ, λ)+DAF(460)×[Kmp(Λ)+Kmp(λ)].
DAF(460)=1Kmp(Λ1)-Kmp(Λ2)×logFP(Λ1, λ)FF(Λ1, λ)-logFP(Λ2, λ)FF(Λ2, λ).
RF(λ)=RF*(λ)10-2DF(λ),
RP(λ)=RP*(λ)10-2DP(λ).
logRP(λ)RF(λ)=logRP*(λ)RF*(λ)+2DRE(460)Kmp(λ),
DRE(460)=0.5Kmp(λ1)-Kmp(λ2)×logRP(λ1)RF(λ1)-logRP(λ2)RF(λ2).
Kmp(Λ)=1D(460)log E(Λ)S(Λ)10-D(460)K(Λ)ΔΛ E(Λ)S(Λ)ΔΛ,
EF(460)10-DF(460)SF(460)=EF(550)10-DF(550)SF(550),
EP(460)10-DP(460)SP(460)=EP(550)10-DP(550)SP(550),
DHFP(460)-DHFP(550)
=-logEP(460)EF(460)+logSP(550)SP(460)-logSF(550)SF(460),
DHFP(460)=-1Kmp(460)-Kmp(550)logEP(460)EF(460).
S(λ)=k[1-10-ω(λ)Dvp(550)],
logSP(550)SP(460)-logSF(550)SF(460)
-0.347[Dvp,F(550)-Dvp,P(550)].
logRp(λ)RF(λ)=logRP*(λ)RF*(λ)+ndme(460)Kme(λ)+2DRE(460)Kmp(λ),
DRE,c(460)=DRE(460)-n2dme(460)×Kme(470)-Kme(550)Kmp(470)-Kmp(550).
DAF,c(460)=DAF(460)-mdme(460)×Kme(470)-Kme(550)Kmp(470)-Kmp(550),
DAF(460)
Dmp(460)-1Kmp(470)-Kmp(550)×log1-Sa(550, λ)FF(550, λ)-log1-Sa(470, λ)FF(470, λ).
DRE(460)
Dmp(460)-0.5Kmp(470)-Kmp(550)×log1-Ra(550)RF(550)-log1-Ra(470)RF(470),
Ra=Ψ-1Ψ/[RF(550)]-1/[RF(470)]
withΨ=10-2[DAF,c(460)-DRE,c(460)][Kmp(470)-Kmp(550)],
DAF(460)DAF(460)+k log(e)Kmp(Λ1)-Kmp(Λ2)×Δ(Λ1, λ)FP*(Λ1, λ)-Δ(Λ2, λ)FP*(Λ2, λ).
DAF=log0RA(r)P(r)rΔr-log0RA(r)P(r)10-D(r)rΔr,
At F:FF(470, 710)=81±44 AFU
FF(550, 710)=136±62 AFU
At P:FP(470, 710)=310±129 AFU
FP(550, 710)=214±91 AFU
At F:RF(470)=0.61%±0.26%
RF(550)=1.66%±0.61%
At P:RP(470)=2.74%±0.89%
RP(550)=3.10%±0.91%
ΔDSa(470, 620){1-[FF(470, 620)/FF(470, λdet)]exp[-α(λdet-620)]}.
RF(λ)=Ra(λ)+RF*(λ)10-2Kmp(λ)DAF,c(460).

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