Measuring macular pigment optical density in vivo: a review of techniques

Review Article

Abstract

Background

Macular pigment has been the focus of much attention in recent years, as a potential modifiable risk factor for age-related macular degeneration. This interest has been heightened by the ability to measure macular pigment optical density (MPOD) in vivo.

Method

A systematic literature search was undertaken to identify all available papers that have used in vivo MPOD techniques. The papers were reviewed, and all relevant information was incorporated into this article.

Results

Measurement of MPOD is achievable with a wide range of techniques, which are typically categorized into one of two groups: psychophysical (requiring a response from the subject) or objective (requiring minimal input from the subject). The psychophysical methods include heterochromatic flicker photometry and minimum motion photometry. The objective methods include fundus reflectometry, fundus autofluorescence, resonance Raman spectroscopy and visual evoked potentials. Even within the individual techniques, there is often much variation in how data is obtained and processed.

Conclusion

This review comprehensively details the procedure, instrumentation, assumptions, validity and reliability of each MPOD measurement technique currently available, along with their respective advantages and disadvantages. This leads us to conclude that development of a commercial instrument, based on fundus reflectometry or fundus autofluorescence, would be beneficial to macular pigment research and would support MPOD screening in a clinical setting.

Keywords

Fundus autofluorescence Fundus reflectometry Heterochromatic flicker photometry Macular pigment Macular pigment optical density Motion photometry Raman spectroscopy 

References

  1. 1.
    Bone RA, Landrum JT, Hime GW, Cains A, Zamor J (1993) Stereochemistry of the human macular carotenoids. Invest Ophthalmol Vis Sci 34:2033–2040PubMedGoogle Scholar
  2. 2.
    Malinow MR, Feeneyburns L, Peterson LH, Klein ML, Neuringer M (1980) Diet-related macular anomalies in monkeys. Invest Ophthalmol Vis Sci 19:857–863PubMedGoogle Scholar
  3. 3.
    Neuringer M, Sandstrom MM, Johnson EJ, Snodderly DM (2004) Nutritional manipulation of primate retinas, I: effects of lutein or zeaxanthin supplements on serum and macular pigment in xanthophyll-free rhesus monkeys. Invest Ophthalmol Vis Sci 45:3234–3243PubMedGoogle Scholar
  4. 4.
    Sommerburg O, Keunen JEE, Bird AC, van Kuijk F (1998) Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes. Br J Ophthalmol 82:907–910PubMedGoogle Scholar
  5. 5.
    Snodderly DM, Auran JD, Delori FC (1984) The macular pigment.II. Spatial distribution in primate retinas. Invest Ophthalmol Vis Sci 25:674–685PubMedGoogle Scholar
  6. 6.
    Snodderly DM, Brown PK, Delori FC, Auran JD (1984) The macular pigment.I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas. Invest Ophthalmol Vis Sci 25:660–673PubMedGoogle Scholar
  7. 7.
    Bone RA, Landrum JT, Fernandez L, Tarsis SL (1988) Analysis of the macular pigment by HPLC — retinal distribution and age study. Invest Ophthalmol Vis Sci 29:843–849PubMedGoogle Scholar
  8. 8.
    Trieschmann M, van Kuijk F, Alexander R, Hermans P, Luthert P, Bird AC, Pauleikhoff D (2008) Macular pigment in the human retina: histological evaluation of localization and distribution. Eye 22:132–137PubMedGoogle Scholar
  9. 9.
    Bone RA, Landrum JT, Cains A (1992) Optical density spectra of the macular pigment in vivo and in vitro. Vision Res 32:105–110PubMedGoogle Scholar
  10. 10.
    Ham WT, Mueller HA, Sliney DH (1976) Retinal sensitivity to damage from short wavelength light. Nature 260:153–155PubMedGoogle Scholar
  11. 11.
    Hammond BR, Caruso-Avery M (2000) Macular pigment optical density in a southwestern sample. Invest Ophthalmol Vis Sci 41:1492–1497PubMedGoogle Scholar
  12. 12.
    Landrum JT, Bone RA (2001) Lutein, zeaxanthin, and the macular pigment. Arch Biochem Biophys 385:28–40PubMedGoogle Scholar
  13. 13.
    Khachik F, Bernstein PS, Garland DL (1997) Identification of lutein and zeaxanthin oxidation products in human and monkey retinas. Invest Ophthalmol Vis Sci 38:1802–1811PubMedGoogle Scholar
  14. 14.
    Leibowitz HM, Krueger DE, Maunder LR, Milton RC, Kini MM, Kahn HA, Nickerson RJ, Pool J, Colton TL, Ganley JP, Loewenstein JI, Dawber TR (1980) The Framingham Eye Study monograph: an ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973–1975. Surv Ophthalmol 24:335–610PubMedGoogle Scholar
  15. 15.
    Klein R, Klein BEK, Linton KLP (1992) Prevalence of age-related maculopathy — the Beaver Dam Eye Study. Ophthalmology 99:933–943PubMedGoogle Scholar
  16. 16.
    Mitchell P, Smith W, Attebo K, Wang JJ (1995) Prevalence of age-related maculopathy in Australia — the Blue Mountains Eye Study. Ophthalmology 102:1450–1460PubMedGoogle Scholar
  17. 17.
    Beatty S, Murray IJ, Henson DB, Carden D, Koh HH, Boulton ME (2001) Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci 42:439–446PubMedGoogle Scholar
  18. 18.
    Bone RA, Landrum JT, Mayne ST, Gomez CM, Tibor SE, Twaroska EE (2001) Macular pigment in donor eyes with and without AMD: A case-control study. Invest Ophthalmol Vis Sci 42:235–240PubMedGoogle Scholar
  19. 19.
    Trieschmann M, Spital G, Lommatzsch A, van Kuijk E, Fitzke F, Bird AC, Pauleikhoff D (2003) Macular pigment: quantitative analysis on autofluorescence images. Graefes Arch Clin Exp Ophthalmol 241:1006–1012PubMedGoogle Scholar
  20. 20.
    Ciulla TA, Hammond BR (2004) Macular pigment density and aging, assessed in the normal elderly and those with cataracts and age-related macular degeneration. Am J Ophthalmol 138:582–587PubMedGoogle Scholar
  21. 21.
    LaRowe TL, Mares JA, Snodderly DM, Klein ML, Wooten BR, Chappell R, Grp CMPS (2008) Macular pigment density and age-related maculopathy in the carotenoids in age-related eye disease study — an ancillary study of the women's health initiative. Ophthalmology 115:876–883PubMedGoogle Scholar
  22. 22.
    Bone RA, Landrum JT, Tarsis SL (1985) Preliminary identification of the human macular pigment. Vision Res 25:1531–1535PubMedGoogle Scholar
  23. 23.
    Handelman GJ, Dratz EA, Reay CC, Vankuijk F (1988) Carotenoids in the human macula and whole retina. Invest Ophthalmol Vis Sci 29:850–855PubMedGoogle Scholar
  24. 24.
    Handelman GJ, Snodderly DM, Krinsky NI, Russett MD, Adler AJ (1991) Biological control of primate macular pigment — biochemical and densitometric studies. Invest Ophthalmol Vis Sci 32:257–267PubMedGoogle Scholar
  25. 25.
    Wüstemeyer H, Moessner A, Jahn C, Wolf S (2003) Macular pigment density in healthy subjects quantified with a modified confocal scanning laser ophthalmoscope. Graefes Arch Clin Exp Ophthalmol 241:647–651PubMedGoogle Scholar
  26. 26.
    van de Kraats J, Kanis MJ, Genders SW, van Norren D (2008) Lutein and zeaxanthin measured separately in the living human retina with fundus reflectometry. Invest Ophthalmol Vis Sci 49:5568–5573PubMedGoogle Scholar
  27. 27.
    Brown PK, Wald G (1963) Visual pigments in human and monkey retinas. Nature 200:37–43PubMedGoogle Scholar
  28. 28.
    Bone RA, Sparrock JM (1971) Comparison of macular pigment densities in human eyes. Vision Res 11:1057–1064PubMedGoogle Scholar
  29. 29.
    Stabell U, Stabell B (1980) Variation in density of macular pigmentation and in short-wave cone sensitivity with eccentricity. J Opt Soc Am 70:706–711PubMedGoogle Scholar
  30. 30.
    Pease PL, Adams AJ (1983) Macular pigment difference spectrum from sensitivity measures of a single cone mechanism. Am J Optom Physiol Opt 60:667–672PubMedGoogle Scholar
  31. 31.
    Pease PL, Adams AJ, Nuccio E (1987) Optical density of human macular pigment. Vision Res 27:705–710PubMedGoogle Scholar
  32. 32.
    Ruddock KH (1963) Evidence for macular pigmentation from colour matching data. Vision Res 61:417–429PubMedGoogle Scholar
  33. 33.
    Moreland JD, Bhatt P (1984) Retinal distribution of macular pigment. Doc Ophthalmol Proc Ser 39:127–132Google Scholar
  34. 34.
    Moreland JD, Alexander EC (1997) Effect of macular pigment on colour matching with field sizes in the 1° to 10° range. Doc Ophthalmol Proc Ser 59:363–368Google Scholar
  35. 35.
    Davies NP, Morland AB (2002) Color matching in diabetes: optical density of the crystalline lens and macular pigments. Invest Ophthalmol Vis Sci 43:281–289PubMedGoogle Scholar
  36. 36.
    Bone RA (1980) The role of the macular pigment in the detection of polarized light. Vision Res 20:213–220PubMedGoogle Scholar
  37. 37.
    Moreland JD, Robson AG, Soto-Leon N, Kulikowski JJ (1998) Macular pigment and the colour-specificity of visual evoked potentials. Vision Res 38:3241–3245PubMedGoogle Scholar
  38. 38.
    Moreland JD, Robson AG, Kulikowski JJ (2001) Macular pigment assessment using a colour monitor. Color Res Appl 26:S261–S263Google Scholar
  39. 39.
    Robson AG, Moreland JD, Pauleikhoff D, Morrissey T, Holder GE, Fitzke FW, Bird AC, van Kuijk F (2003) Macular pigment density and distribution: comparison of fundus autofluorescence with minimum motion photometry. Vision Res 43:1765–1775PubMedGoogle Scholar
  40. 40.
    Moreland JD (2004) Macular pigment assessment by motion photometry. Arch Biochem Biophys 430:143–148PubMedGoogle Scholar
  41. 41.
    Robson AG, Parry NRA (2008) Measurement of macular pigment optical density and distribution using the steady-state visual evoked potential. Vis Neurosci 25:575–583PubMedGoogle Scholar
  42. 42.
    Werner JS, Donnelly SK, Kliegl R (1987) Aging and human macular pigment density. Appended with translations from the work of Max Schultze and Ewald Hering. Vision Res 27:257–268PubMedGoogle Scholar
  43. 43.
    Hammond BR, Fuld K (1992) Interocular differences in macular pigment density. Invest Ophthalmol Vis Sci 33:350–355PubMedGoogle Scholar
  44. 44.
    Hammond BR, Wooten BR, Snodderly DM (1997) Individual variations in the spatial profile of human macular pigment. J Opt Soc Am A Opt Image Sci Vis 14:1187–1196PubMedGoogle Scholar
  45. 45.
    Landrum JT, Bone RA, Joa H, Kilburn MD, Moore LL, Sprague KE (1997) A one year study of the macular pigment: the effect of 140 days of a lutein supplement. Exp Eye Res 65:57–62PubMedGoogle Scholar
  46. 46.
    Wooten BR, Hammond BR, Land RI, Snodderly DM (1999) A practical method for measuring macular pigment optical density. Invest Ophthalmol Vis Sci 40:2481–2489PubMedGoogle Scholar
  47. 47.
    Beatty S, Koh HH, Carden D, Murray IJ (2000) Macular pigment optical density measurement: a novel compact instrument. Ophthalmic Physiol Opt 20:105–111PubMedGoogle Scholar
  48. 48.
    Mellerio J, Ahmadi-Lari S, van Kuijk F, Pauleikhoff D, Bird A, Marshall J (2002) A portable instrument for measuring macular pigment with central fixation. Curr Eye Res 25:37–47PubMedGoogle Scholar
  49. 49.
    Bone RA, Landrum JT (2004) Heterochromatic flicker photometry. Arch Biochem Biophys 430:137–142PubMedGoogle Scholar
  50. 50.
    Snodderly DM, Mares JA, Wooten BR, Oxton L, Gruber M, Ficek T (2004) Macular pigment measurement by heterochromatic flicker photometry in older subjects: the carotenoids and age-related eye disease study. Invest Ophthalmol Vis Sci 45:531–538PubMedGoogle Scholar
  51. 51.
    Iannaccone A, Mura M, Gallaher KT, Johnson EJ, Todd WA, Kenyon E, Harris TL, Harris T, Satterfield S, Johnson KC, Kritchevsky SB, Study HA (2007) Macular pigment optical density in the elderly: findings in a large biracial midsouth population sample. Invest Ophthalmol Vis Sci 48:1458–1465PubMedGoogle Scholar
  52. 52.
    Stringham JM, Hammond BR, Nolan JM, Wooten BR, Mammen A, Smollon W, Snodderly DM (2008) The utility of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment in patients with age-related macular degeneration. Exp Eye Res 87:445–453PubMedGoogle Scholar
  53. 53.
    van der Veen RL, Berendschot TT, Hendrikse F, Carden D, Makridaki M, Murray IJ (2009) A new desktop instrument for measuring macular pigment optical density based on a novel technique for setting flicker thresholds. Ophthalmic Physiol Opt 29:127–137PubMedGoogle Scholar
  54. 54.
    Hammond BR, Wooten BR, Smollon B (2005) Assessment of the validity of in vivo methods of measuring human macular pigment optical density. Optom Vis Sci 82:387–404PubMedGoogle Scholar
  55. 55.
    Viner C (2003) Measuring macular pigment levels: an in-practice procedure? Optician 226:24–26Google Scholar
  56. 56.
    Delori FC, Goger DG, Hammond BR, Snodderly DM, Burns SA (2001) Macular pigment density measured by autofluorescence spectrometry: comparison with reflectometry and heterochromatic flicker photometry. J Opt Soc Am A Opt Image Sci Vis 18:1212–1230PubMedGoogle Scholar
  57. 57.
    Neelam K, O'Gorman N, Nolan J, O'Donovan O, Wong HB, Eong KGA, Beatty S (2005) Measurement of macular pigment: Raman spectroscopy versus heterochromatic flicker photometry. Invest Ophthalmol Vis Sci 46:1023–1032PubMedGoogle Scholar
  58. 58.
    van de Kraats J, Berendschot T, Valen S, van Norren D (2006) Fast assessment of the central macular pigment density with natural pupil using the macular pigment reflectometer. J Biomed Opt 11:064031PubMedGoogle Scholar
  59. 59.
    Bone RA, Brener B, Gibert JC (2007) Macular pigment, photopigments, and melanin: distributions in young subjects determined by four-wavelength reflectometry. Vision Res 47:3259–3268PubMedGoogle Scholar
  60. 60.
    Canovas R, Lima VC, Garcia P, Morini C, Prata TS, Rosen RB (2010) Comparison between macular pigment optical density measurements using two-wavelength autofluorescence and heterochromatic flicker photometry techniques. Invest Ophthalmol Vis Sci 51:3152–3156PubMedGoogle Scholar
  61. 61.
    Werner JS, Wooten BR (1979) Opponent chromatic response functions for an average observer. Percept Psychophys 25:371–374PubMedGoogle Scholar
  62. 62.
    Tang CY, Yip HS, Poon MY, Yau WL, Yap MKH (2004) Macular pigment optical density in young Chinese adults. Ophthalmic Physiol Opt 24:586–593PubMedGoogle Scholar
  63. 63.
    Loane E, Stack J, Beatty S, Nolan JM (2007) Measurement of macular pigment optical density using two different heterochromatic flicker photometers. Curr Eye Res 32:555–564PubMedGoogle Scholar
  64. 64.
    Kirby ML, Galea M, Loane E, Stack J, Beatty S, Nolan JM (2009) Foveal anatomic associations with the secondary peak and the slope of the macular pigment spatial profile. Invest Ophthalmol Vis Sci 50:1383–1391PubMedGoogle Scholar
  65. 65.
    Snodderly DM, Hammond BR (1999) In vivo psychophysical assessment of nutritional and environmental influences on human ocular tissues: lens and macular pigment. In: Taylor A (ed) Nutritional and environmental influences on the eye. CRC Press, Boca Raton, FL, pp 251–273Google Scholar
  66. 66.
    Werner JS, Bieber ML, Schefrin BE (2000) Senescence of foveal and parafoveal cone sensitivities and their relations to macular pigment density. J Opt Soc Am A Opt Image Sci Vis 17:1918–1932PubMedGoogle Scholar
  67. 67.
    Hammond BR, Johnson EJ, Russell RM, Krinsky NI, Yeum KJ, Edwards RB, Snodderly DM (1997) Dietary modification of human macular pigment density. Invest Ophthalmol Vis Sci 38:1795–1801PubMedGoogle Scholar
  68. 68.
    Bone RA, Landrum JT, Gibert JC (2004) Macular pigment and the edge hypothesis of flicker photometry. Vision Res 44:3045–3051PubMedGoogle Scholar
  69. 69.
    Burke JD, Curran-Celentano J, Wenzel AJ (2005) Diet and serum carotenoid concentrations affect macular pigment optical density in adults 45 years and older. J Nutr 135:1208–1214PubMedGoogle Scholar
  70. 70.
    Lam RF, Rao SK, Fan DSP, Lau FTC, Lam DSC (2005) Macular pigment optical density in a Chinese sample. Curr Eye Res 30:799–805PubMedGoogle Scholar
  71. 71.
    Wooten BR, Hammond BR (2005) Spectral absorbance and spatial distribution of macular pigment using heterochromatic flicker photometry. Optom Vis Sci 82:378–386PubMedGoogle Scholar
  72. 72.
    Stringham JM, Hammond BR (2007) The glare hypothesis of macular pigment function. Optom Vis Sci 84:859–864PubMedGoogle Scholar
  73. 73.
    Wenzel AJ, Sheehan JP, Burke JD, Lefsrud MG, Curran-Celentano J (2007) Dietary intake and serum concentrations of lutein and zeaxanthin, but not macular pigment optical density, are related in spouses. Nutr Res 27:462–469Google Scholar
  74. 74.
    Wenzel AJ, Sheehan JP, Gerweck C, Stringham JM, Fuld K, Curran-Celentano J (2007) Macular pigment optical density at four retinal loci during 120 days of lutein supplementation. Ophthalmic Physiol Opt 27:329–335PubMedGoogle Scholar
  75. 75.
    Nolan JM, Stringham JM, Beatty S, Snodderly DM (2008) Spatial profile of macular pigment and its relationship to foveal architecture. Invest Ophthalmol Vis Sci 49:2134–2142PubMedGoogle Scholar
  76. 76.
    Stringham JM, Hammond BR (2008) Macular pigment and visual performance under glare conditions. Optom Vis Sci 85:82–88PubMedGoogle Scholar
  77. 77.
    Stringham JM, Hammond BR, Wooten BR, Snodderly DM (2006) Compensation for light loss resulting from filtering by macular pigment: relation to the S-cone pathway. Optom Vis Sci 83:887–894PubMedGoogle Scholar
  78. 78.
    Connolly EE, Beatty S, Thurnham DI, Loughman J, Howard AN, Stack J, Nolan JM (2010) Augmentation of macular pigment following supplementation with all three macular carotenoids: an exploratory study. Curr Eye Res 35:335–351PubMedGoogle Scholar
  79. 79.
    Loane E, McKay GJ, Nolan JM, Beatty S (2010) Apolipoprotein E genotype is associated with macular pigment optical density. Invest Ophthalmol Vis Sci 51:2636–2643PubMedGoogle Scholar
  80. 80.
    Ciulla TA, Curran-Celantano J, Cooper DA, Hammond BR, Danis RP, Pratt LM, Riccardi KA, Filloon TG (2001) Macular pigment optical density in a Midwestern sample. Ophthalmology 108:730–737PubMedGoogle Scholar
  81. 81.
    Ciulla TA, Hammond BR, Yung CW, Pratt LM (2001) Macular pigment optical density before and after cataract extraction. Invest Ophthalmol Vis Sci 42:1338–1341PubMedGoogle Scholar
  82. 82.
    Hammond BR, Fuld K, Curran-Celentano J (1995) Macular pigment density in monozygotic twins. Invest Ophthalmol Vis Sci 36:2531–2541PubMedGoogle Scholar
  83. 83.
    Nolan JM, Stack J, Donovan OO, Loane E, Beatty S (2007) Risk factors for age-related maculopathy are associated with a relative lack of macular pigment. Exp Eye Res 84:61–74PubMedGoogle Scholar
  84. 84.
    Nolan JM, Stack J, O'Connell E, Beatty S (2007) The relationships between macular pigment optical density and its constituent carotenoids in diet and serum. Invest Ophthalmol Vis Sci 48:571–582PubMedGoogle Scholar
  85. 85.
    Schalch W, Cohn W, Barker FM, Kopcke W, Mellerio J, Bird AC, Robson AG, Fitzke FF, van Kuijk FJGM (2007) Xanthophyll accumulation in the human retina during supplementation with lutein or zeaxanthin - the LUXEA (LUtein Xanthophyll Eye Accumulation) study. Arch Biochem Biophys 458:128–135PubMedGoogle Scholar
  86. 86.
    Hammond BR, Wooten BR (2005) CFF thresholds: relation to macular pigment optical density. Ophthalmic Physiol Opt 25:315–319PubMedGoogle Scholar
  87. 87.
    Cooper DA, Curran-Celentano J, Ciulla TA, Hammond BR, Danis RB, Pratt LM, Riccardi KA, Filloon TG (2000) Olestra consumption is not associated with macular pigment optical density in a cross-sectional volunteer sample in Indianapolis. J Nutr 130:642–647PubMedGoogle Scholar
  88. 88.
    Curran-Celentano J, Hammond BR, Ciulla TA, Cooper DA, Pratt LM, Danis RB (2001) Relation between dietary intake, serum concentrations, and retinal concentrations of lutein and zeaxanthin in adults in a Midwest population. Am J Clin Nutr 74:796–802PubMedGoogle Scholar
  89. 89.
    Bone RA, Landrum JT, Guerra LH, Ruiz CA (2003) Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans. J Nutr 133:992–998PubMedGoogle Scholar
  90. 90.
    Bone RA, Landrum JT, Cao Y, Howard AN, Alvarez-Calderon F (2007) Macular pigment response to a supplement containing meso-zeaxanthin, lutein and zeaxanthin. Nutr Metab 4:12Google Scholar
  91. 91.
    Koh HH, Murray IJ, Nolan D, Carden D, Feather J, Beatty S (2004) Plasma and macular response to lutein supplement in subjects with and without age-related maculopathy: a pilot study. Exp Eye Res 79:21–27PubMedGoogle Scholar
  92. 92.
    Robson AG, Holder GE, Moreland JD, Kulikowski JJ (2006) Chromatic VEP assessment of human macular pigment: comparison with minimum motion and minimum flicker profiles. Vis Neurosci 23:275–283PubMedGoogle Scholar
  93. 93.
    Engles M, Wooten B, Hammond B (2007) Macular pigment: a test of the acuity hypothesis. Invest Ophthalmol Vis Sci 48:2922–2931PubMedGoogle Scholar
  94. 94.
    Rodriguez-Carmona M, Kvansakul J, Harlow JA, Kopcke W, Schalch W, Barbur JL (2006) The effects of supplementation with lutein and/or zeaxanthin on human macular pigment density and colour vision. Ophthalmic Physiol Opt 26:137–147PubMedGoogle Scholar
  95. 95.
    Kvansakul J, Rodriguez-Carmona M, Edgar DF, Barker FM, Kopcke W, Schalch W, Barbur JL (2006) Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance. Ophthalmic Physiol Opt 26:362–371PubMedGoogle Scholar
  96. 96.
    Makridaki M, Carden D, Murray IJ (2009) Macular pigment measurement in clinics: controlling the effect of the ageing media. Ophthalmic Physiol Opt 29:338–344PubMedGoogle Scholar
  97. 97.
    Nolan JM, Kenny R, O'Regan C, Cronin H, Loughman J, Connolly EE, Kearney P, Loane E, Beatty S (2010) Macular pigment optical density in an ageing Irish population: the Irish longitudinal study on ageing. Ophthalmic Res 44:131–139PubMedGoogle Scholar
  98. 98.
    Wüstemeyer H, Jahn C, Nestler A, Barth T, Wolf S (2002) A new instrument for the quantification of macular pigment density: first results in patients with AMD and healthy subjects. Graefes Arch Clin Exp Ophthalmol 240:666–671PubMedGoogle Scholar
  99. 99.
    Curcio CA, Allen KA, Sloan KR, Lerea CL, Hurley JB, Klock IB, Milam AH (1991) Distribution and morphology of human cone photoreceptors stained with anti-blue opsin. J Comp Neurol 312:610–624PubMedGoogle Scholar
  100. 100.
    Curcio CA, Sloan KR (1992) Packing geometry of human cone photoreceptors - variation with eccentricity and evidence for local anisotropy. Vis Neurosci 9:169–180PubMedGoogle Scholar
  101. 101.
    Curcio CA, Sloan KR, Kalina RE, Hendrickson AE (1990) Human photoreceptor topography. J Comp Neurol 292:497–523PubMedGoogle Scholar
  102. 102.
    Cicerone CM, Nerger JL (1989) The relative numbers of long-wavelength-sensitive to middle-wavelength-sensitive cones in the human fovea centralis. Vision Res 29:115–128PubMedGoogle Scholar
  103. 103.
    Nerger JL, Cicerone CM (1992) The ratio of L-cones to M-cones in the human parafoveal retina. Vision Res 32:879–888PubMedGoogle Scholar
  104. 104.
    Knau H, Jagle H, Sharpe LT (2001) L/M cone ratios as a function of retinal eccentricity. Color Res Appl 26:S128–S132Google Scholar
  105. 105.
    Hammond BR, Wooten BR, Snodderly DM (1998) Preservation of visual sensitivity of older subjects: association with macular pigment density. Invest Ophthalmol Vis Sci 39:397–406PubMedGoogle Scholar
  106. 106.
    Brindley GS, Du Croz JJ, Rushton WA (1966) The flicker fusion frequency of the blue-sensitive mechanism of colour vision. J Physiol 183:497–500PubMedGoogle Scholar
  107. 107.
    Nolan J, O'Donovan O, Kavanagh H, Stack J, Harrison M, Muldoon A, Mellerio J, Beatty S (2004) Macular pigment and percentage of body fat. Invest Ophthalmol Vis Sci 45:3940–3950PubMedGoogle Scholar
  108. 108.
    Chen SF, Chang Y, Wu JC (2001) The spatial distribution of macular pigment in humans. Curr Eye Res 23:422–434PubMedGoogle Scholar
  109. 109.
    Berendschot T, van Norren D (2004) Objective determination of the macular pigment optical density using fundus reflectance spectroscopy. Arch Biochem Biophys 430:149–155PubMedGoogle Scholar
  110. 110.
    Bernstein PS, Zhao DY, Sharifzadeh M, Ermakov IV, Gellermann W (2004) Resonance Raman measurement of macular carotenoids in the living human eye. Arch Biochem Biophys 430:163–169PubMedGoogle Scholar
  111. 111.
    Gellermann W, Bernstein PS (2004) Noninvasive detection of macular pigments in the human eye. J Biomed Opt 9:75–85PubMedGoogle Scholar
  112. 112.
    Bhosale P, Zhao DY, Bernstein PS (2007) HPLC measurement of ocular carotenoid levels in human donor eyes in the lutein supplementation era. Invest Ophthalmol Vis Sci 48:543–549PubMedGoogle Scholar
  113. 113.
    Hammond BR, Ciulla TA, Snodderly DM (2002) Macular pigment density is reduced in obese subjects. Invest Ophthalmol Vis Sci 43:47–50PubMedGoogle Scholar
  114. 114.
    Gallaher KT, Mura M, Todd WA, Harris TL, Kenyon E, Harris T, Johnson KC, Satterfield S, Kritchevsky SB, Iannaccone A, Hlth ABCS (2007) Estimation of macular pigment optical density in the elderly: test–retest variability and effect of optical blur in pseudophakic subjects. Vision Res 47:1253–1259PubMedGoogle Scholar
  115. 115.
    Snodderly DM, Handelman GJ, Adler AJ (1991) Distribution of individual macular pigment carotenoids in central retina of macaque and squirrel-monkeys. Invest Ophthalmol Vis Sci 32:268–279PubMedGoogle Scholar
  116. 116.
    Berendschot T, van Norren D (2006) Macular pigment shows ringlike structures. Invest Ophthalmol Vis Sci 47:709–714PubMedGoogle Scholar
  117. 117.
    Delori FC, Goger DG, Keilhauer C, Salvetti P, Staurenghi G (2006) Bimodal spatial distribution of macular pigment: evidence of a gender relationship. J Opt Soc Am A Opt Image Sci Vis 23:521–538PubMedGoogle Scholar
  118. 118.
    Wyszecki G, Stiles WS (1982) Color Science: Concepts and Methods, Quantitative Data and Formulae. The eye. Wiley, New York, pp 112–114Google Scholar
  119. 119.
    Bartlett H, Acton J, Eperjesi F (2010) Clinical evaluation of the MacuScope macular pigment densitometer. Br J Ophthalmol 94:328–331PubMedGoogle Scholar
  120. 120.
    Hagen S, Krebs I, Glittenberg C, Binder S (2010) Repeated measures of macular pigment optical density to test reproducibility of heterochromatic flicker photometry. Acta Ophthalmol 88:207–211PubMedGoogle Scholar
  121. 121.
    van der Veen RLP, Berendschot T, Makridaki M, Hendrikse F, Carden D, Murray IJ (2009) Correspondence between retinal reflectometry and a flicker-based technique in the measurement of macular pigment spatial profiles. J Biomed Opt 14:064046PubMedGoogle Scholar
  122. 122.
    Johnson EJ, Chung HY, Caldarella SM, Snodderly DM (2008) The influence of supplemental lutein and docosahexaenoic acid on serum, lipoproteins, and macular pigmentation. Am J Clin Nutr 87:1521–1529PubMedGoogle Scholar
  123. 123.
    Troxler DIPV (1804) Über das Verschwinden gegebener Gegenstände innerhalb unseres Gesichtskreises. In: Himly J, Schmidt JA (eds) Ophthalmologische Bibliothek. Fromann, Jena, pp 1–53Google Scholar
  124. 124.
    Stumpf P (1911) On the dependence of the visual sensation of movement and its negative aftereffect on the stimulation processes on the retina. Z Psychol 59:321–330Google Scholar
  125. 125.
    Todorović D (1996) A gem from the past: Pleikart Stumpf's (1911) anticipation of the aperture problem, Reichardt detectors, and perceived motion loss at equiluminance. Perception 25:1235–1242Google Scholar
  126. 126.
    Moreland JD (1980) A modified Moreland anomaloscope using optokinetic nystagmus to define colour matches objectively. In: Verriest G (ed) Colour vision deficiencies V. Hilger, Bristol, pp 189–191Google Scholar
  127. 127.
    Moreland JD (1982) Spectral sensitivity measurements by motion photometry. Doc Ophthalmol Proc Ser 33:61–66Google Scholar
  128. 128.
    Anstis SM, Cavanagh P (1983) A minimum motion technique for judging equiluminance. In: Mollon JD, Sharpe LT (eds) Colour vision: physiology and psychophysics. Academic Press, London, pp 155–166Google Scholar
  129. 129.
    Robson AG, Harding G, van Kuijk F, Pauleikhoff D, Holder GE, Bird AC, Fitzke FW, Moreland JD (2005) Comparison of fundus autofluorescence and minimum-motion measurements of macular pigment distribution profiles derived from identical retinal areas. Perception 34:1029–1034PubMedGoogle Scholar
  130. 130.
    West P, Mellerio J (2005) Measuring MPOD using a CRT display [online]. http://www.crsltd.com/research-topics/macular-pigment/index.html and http://www.crsltd.com/catalog/metropsis/MP.html. Accessed 1 May 2009
  131. 131.
    Brindley GS, Willmer EN (1952) The reflexion of light from the macular and peripheral fundus oculi in man. J Physiol 116:350–356PubMedGoogle Scholar
  132. 132.
    Berendschot T, DeLint PJ, van Norren D (2003) Fundus reflectance — historical and present ideas. Prog Retin Eye Res 22:171–200PubMedGoogle Scholar
  133. 133.
    van Norren D, Tiemeijer LF (1986) Spectral reflectance of the human eye. Vision Res 26:313–320PubMedGoogle Scholar
  134. 134.
    Delori FC, Pflibsen KP (1989) Spectral reflectance of the human ocular fundus. Appl Opt 28:1061–1077PubMedGoogle Scholar
  135. 135.
    Elsner AE, Burns SA, Beausencourt E, Weiter JJ (1998) Foveal cone photopigment distribution: small alterations associated with macular pigment distribution. Invest Ophthalmol Vis Sci 39:2394–2404PubMedGoogle Scholar
  136. 136.
    Berendschot T, Goldbohm RA, Klopping WAA, van de Kraats J, van Norel J, van Norren D (2000) Influence of lutein supplementation on macular pigment, assessed with two objective techniques. Invest Ophthalmol Vis Sci 41:3322–3326PubMedGoogle Scholar
  137. 137.
    Bour LJ, Koo L, Delori FC, Apkarian P, Fulton AB (2002) Fundus photography for measurement of macular pigment density distribution in children. Invest Ophthalmol Vis Sci 43:1450–1455PubMedGoogle Scholar
  138. 138.
    Cardinault N, Gorrand JM, Tyssandier V, Grolier P, Rock E, Borel P (2003) Short-term supplementation with lutein affects biomarkers of lutein status similarly in young and elderly subjects. Exp Gerontol 38:573–582PubMedGoogle Scholar
  139. 139.
    van de Kraats J, van Norren D (2008) Directional and nondirectional spectral reflection from the human fovea. J Biomed Opt 13:024010PubMedGoogle Scholar
  140. 140.
    van de Kraats J, Berendschot T, van Norren D (1996) The pathways of light measured in fundus reflectometry. Vision Res 36:2229–2247PubMedGoogle Scholar
  141. 141.
    Berendschot T, van Norren D (2005) On the age dependency of the macular pigment optical density. Exp Eye Res 81:602–609PubMedGoogle Scholar
  142. 142.
    Kanis MJ, Berendschot T, van Norren D (2007) Influence of macular pigment and melanin on incident early AMD in a white population. Graefes Arch Clin Exp Ophthalmol 245:767–773PubMedGoogle Scholar
  143. 143.
    Kanis MJ, Berendschot T, van Norren D (2007) Interocular agreement in melanin and macular pigment optical density. Exp Eye Res 84:934–938PubMedGoogle Scholar
  144. 144.
    Berendschot T, Willemse-Assink JJM, Bastiaanse M, de Jong P, van Norren D (2002) Macular pigment and melanin in age-related maculopathy in a general population. Invest Ophthalmol Vis Sci 43:1928–1932PubMedGoogle Scholar
  145. 145.
    Chang Y, Lee FL, Chen SJ, Chen SF (2002) Optical measurement of human retinal macular pigment and its spatial distribution with age. Med Phys 29:2621–2628PubMedGoogle Scholar
  146. 146.
    Zagers NPA, van de Kraats J, Berendschot T, van Norren D (2002) Simultaneous measurement of foveal spectral reflectance and cone-photoreceptor directionality. Appl Opt 41:4686–4696PubMedGoogle Scholar
  147. 147.
    Zagers NPA, van Norren D (2004) Absorption of the eye lens and macular pigment derived from the reflectance of cone photoreceptors. J Opt Soc Am A Opt Image Sci Vis 21:2257–2268PubMedGoogle Scholar
  148. 148.
    Kanis MJ, Wisse RPL, Berendschot T, van de Kraats J, van Norren D (2008) Foveal cone-photoreceptor integrity in aging macula disorder. Invest Ophthalmol Vis Sci 49:2077–2081PubMedGoogle Scholar
  149. 149.
    Elsner AE, Burns SA, Delori FC, Webb RH (1990) Quantitative reflectometry with the SLO. In: Naseman JE, Burk ROW (eds) Scanning laser ophthalmoscopy and tomography. Quintessenz-Verlag, Munich, pp 109–121Google Scholar
  150. 150.
    Seth R, Gouras P (2004) Assessing macular pigment from SLO images. Doc Ophthalmol 108:197–202PubMedGoogle Scholar
  151. 151.
    Helb HM, Issa PC, Van der Veen RLP, Berendschot T, Scholl HPN, Holz FG (2008) Abnormal macular pigment distribution in type 2 idiopathic macular telangiectasia. Retina 28:808–816PubMedGoogle Scholar
  152. 152.
    Sharifzadeh M, Bernstein PS, Gellermann W (2006) Nonmydriatic fluorescence-based quantitative imaging of human macular pigment distributions. J Opt Soc Am A Opt Image Sci Vis 23:2373–2387PubMedGoogle Scholar
  153. 153.
    Wolf-Schnurrbusch UEK, Roosli N, Weyermann E, Heldner MR, Hohne K, Wolf S (2007) Ethnic differences in macular pigment density and distribution. Invest Ophthalmol Vis Sci 48:3783–3787PubMedGoogle Scholar
  154. 154.
    Bernstein PS, Delori FC, Richer S, van Kuijk FJM, Wenzel AJ (2010) The value of measurement of macular carotenoid pigment optical densities and distributions in age-related macular degeneration and other retinal disorders. Vision Res 50:716–728PubMedGoogle Scholar
  155. 155.
    Delori FC (1994) Spectrophotometer for noninvasive measurement of intrinsic fluorescence and reflectance of the ocular fundus. Appl Opt 33:7439–7452PubMedGoogle Scholar
  156. 156.
    Delori FC, Dorey CK, Staurenghi G, Arend O, Goger DG, Weiter JJ (1995) In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest Ophthalmol Vis Sci 36:718–729PubMedGoogle Scholar
  157. 157.
    von Ruckmann A, Fitzke FW, Bird AC (1995) Distribution of fundus autofluorescence with a scanning laser ophthalmoscope. Br J Ophthalmol 79:407–412Google Scholar
  158. 158.
    Delori FC (2004) Autofluorescence method to measure macular pigment optical densities fluorometry and autofluorescence imaging. Arch Biochem Biophys 430:156–162PubMedGoogle Scholar
  159. 159.
    Schmitz-Valckenberg S, Holz FG, Bird AC, Spaide RF (2008) Fundus autofluorescence imaging — review and perspectives. Retina 28:385–409PubMedGoogle Scholar
  160. 160.
    Liew SHM, Gilbert CE, Spector TD, Mellerio J, Van Kuijk FJ, Beatty S, Fitzke F, Marshall J, Hammond CJ (2006) Central retinal thickness is positively correlated with macular pigment optical density. Exp Eye Res 82:915–920PubMedGoogle Scholar
  161. 161.
    Trieschmann M, Heimes B, Hense HW, Pauleikhoff D (2006) Macular pigment optical density measurement in autofluorescence imaging: comparison of one- and two-wavelength methods. Graefes Arch Clin Exp Ophthalmol 244:1565–1574PubMedGoogle Scholar
  162. 162.
    Jahn C, Wustemeyer H, Brinkmann C, Trautmann S, Mossner A, Wolf S (2005) Macular pigment density in age-related maculopathy. Graefes Arch Clin Exp Ophthalmol 243:222–227PubMedGoogle Scholar
  163. 163.
    Liew SHM, Gilbert CE, Spector TD, Mellerio J, Marshall J, van Kuijk FJ, Beatty S, Fitzke F, Hammond CJ (2005) Heritability of macular pigment: a twin study. Invest Ophthalmol Vis Sci 46:4430–4436PubMedGoogle Scholar
  164. 164.
    Trieschmann M, Beatty S, Nolan JM, Hense HW, Heimes B, Austermann U, Fobker M, Pauleikhoff D (2007) Changes in macular pigment optical density and serum concentrations of its constituent carotenoids following supplemental lutein and zeaxanthin: the LUNA study. Exp Eye Res 84:718–728PubMedGoogle Scholar
  165. 165.
    Delori FC, Goger DG, Dorey CK (2001) Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects. Invest Ophthalmol Vis Sci 42:1855–1866PubMedGoogle Scholar
  166. 166.
    Bernstein PS, Yoshida MD, Katz NB, McClane RW, Gellermann W (1998) Raman detection of macular carotenoid pigments in intact human retina. Invest Ophthalmol Vis Sci 39:2003–2011PubMedGoogle Scholar
  167. 167.
    Koyama Y, Takatsuka I, Nakata M, Tasumi M (1988) Raman and infrared spectra of the all-trans, 7-cis, 9-cis, 13-cis and 15-cis isomers of beta carotene - key bands distinguishing stretched or terminal-bent configurations from central-bent configurations. J Raman Spectrosc 19:37–49Google Scholar
  168. 168.
    Ermakov IV, McClane RW, Gellermann W, Bernstein PS (2001) Resonant Raman detection of macular pigment levels in the living human retina. Opt Lett 26:202–204PubMedGoogle Scholar
  169. 169.
    Bernstein PS (2002) New insights into the role of the macular carotenoids in age-related macular degeneration. Resonance Raman studies. Pure Appl Chem 74:1419–1425Google Scholar
  170. 170.
    Bernstein PS, Zhao DY, Wintch SW, Ermakov IV, McClane RW, Gellermann W (2002) Resonance Raman measurement of macular carotenoids in normal subjects and in age-related macular degeneration patients. Ophthalmology 109:1780–1787PubMedGoogle Scholar
  171. 171.
    Gellermann W, Ermakov IV, Ermakova MR, McClane RW, Zhao DY, Bernstein PS (2002) In vivo resonant Raman measurement of macular carotenoid pigments in the young and the aging human retina. J Opt Soc Am A Opt Image Sci Vis 19:1172–1186PubMedGoogle Scholar
  172. 172.
    Gellermann W, Ermakov IV, McClane RW, Bernstein PS (2002) Raman imaging of human macular pigments. Opt Lett 27:833–835PubMedGoogle Scholar
  173. 173.
    Zhao DY, Wintch SW, Ermakov IV, Gellermann W, Bernstein PS (2003) Resonance Raman measurement of macular carotenoids in retinal, choroidal, and macular dystrophies. Arch Ophthalmol 121:967–972PubMedGoogle Scholar
  174. 174.
    Ermakov I, Ermakova M, Gellermann W, Bernstein PS (2004) Macular pigment Raman detector for clinical applications. J Biomed Opt 9:139–148PubMedGoogle Scholar
  175. 175.
    Ermakov IV, Sharifzadeh M, Ermakova M, Gellermann W (2005) Resonance Raman detection of carotenoid antioxidants in living human tissue. J Biomed Opt 10:064028PubMedGoogle Scholar
  176. 176.
    Hogg RE, Anderson RS, Stevenson MR, Zlatkova MB, Chakravarthy U (2007) In vivo macular pigment measurements: a comparison of resonance Raman spectroscopy and heterochromatic flicker photometry. Br J Ophthalmol 91:485–490PubMedGoogle Scholar
  177. 177.
    Obana A, Hiramitsu T, Gohto Y, Ohira A, Mizuno S, Hirano T, Bernstein PS, Fujii H, Iseki K, Tanito M, Hotta Y (2008) Macular carotenoid levels of normal subjects and age-related maculopathy patients in a Japanese population. Ophthalmology 115:147–157PubMedGoogle Scholar
  178. 178.
    Sharifzadeh M, Zhao DY, Bernstein PS, Gellermann W (2008) Resonance Raman imaging of macular pigment distributions in the human retina. J Opt Soc Am A Opt Image Sci Vis 25:947–957PubMedGoogle Scholar
  179. 179.
    Hogg RE, Zlatkova MB, Chakravarthy U, Anderson RS (2007) Investigation of the effect of simulated lens yellowing, transparency loss and refractive error on in vivo resonance Raman spectroscopy. Ophthalmic Physiol Opt 27:225–231PubMedGoogle Scholar
  180. 180.
    Bernstein PS, Gellermann W (2003) Author response: assessment of the Raman method of measuring human macular pigment [Letter] [online]. Investigative Ophthalmology & Visual Science. Available at: http://www.iovs.org/cgi/eletters?lookup=by_date&days=9999#74. Accessed 15 September 2009
  181. 181.
    Bernstein PS, Gellermann W (2003) Author response: assessment of the Raman method of measuring human macular pigment (II) [Letter] [online]. Investigative Ophthalmology & Visual Science. Available at: http://www.iovs.org/cgi/eletters?lookup=by_date&days=9999#74. Accessed 15 September 2009
  182. 182.
    Wooten BR, Hammond BR (2003) Assessment of the Raman method of measuring human macular pigment [Letter] [online]. Investigative Ophthalmology & Visual Science. Available at: http://www.iovs.org/cgi/eletters?lookup=by_date&days=9999#73. Accessed 15 September 2009
  183. 183.
    Wooten BR, Hammond BR (2003) Assessment of the Raman method of measuring human macular pigment (II) [Letter] [online]. Investigative Ophthalmology & Visual Science. Available at: http://www.iovs.org/cgi/eletters?lookup=by_date&days=9999#73. Accessed 15 September 2009
  184. 184.
    Hammond BR, Wooten BR (2005) Resonance Raman spectroscopic measurement of carotenoids in the skin and retina. J Biomed Opt 10:054002PubMedGoogle Scholar
  185. 185.
    Gellermann W, Bernstein PS (2006) Assessment of the validity of in vivo methods of measuring human macular pigment optical density [Letter]. Optom Vis Sci 83:254–255PubMedGoogle Scholar
  186. 186.
    Hammond BR, Wooten BR, Smollon B (2006) Assessment of the validity of in vivo methods of measuring human macular pigment optical density — Authors' response [Letter]. Optom Vis Sci 83:256–259Google Scholar
  187. 187.
    Beatty S, van Kuijk F, Chakravarthy U (2008) Macular pigment and age-related macular degeneration: longitudinal data and better techniques of measurement are needed. Invest Ophthalmol Vis Sci 49:843–845PubMedGoogle Scholar
  188. 188.
    Bird AEC, Bressler NM, Bressler SB, Chisholm IH, Coscas G, Davis MD, Dejong P, Klaver CCW, Klein BEK, Klein R, Mitchell P, Sarks JP, Sarks SH, Sourbane G, Taylor HR, Vingerling JR (1995) An international classification and grading system for age-related maculopathy and age-related macular degeneration. Surv Ophthalmol 39:367–374PubMedGoogle Scholar
  189. 189.
    Aleman TS, Duncan JL, Bieber ML, de Castro E, Marks DA, Gardner LM, Steinberg JD, Cideciyan AV, Maguire MG, Jacobson SG (2001) Macular pigment and lutein supplementation in retinitis pigmentosa and Usher syndrome. Invest Ophthalmol Vis Sci 42: 1873–1881Google Scholar
  190. 190.
    Duncan JL, Aleman TS, Gardner LM, De Castro E, Marks DA, Emmons JM, Bieber ML, Steinberg JD, Bennett J, Stone EM, Macdonald IM, Cideciyan AV, Maguire MG, Jacobson SG (2002) Macular pigment and lutein supplementation in choroideremia. Exp Eye Res 74:371–381Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Olivia Howells
    • 1
  • Frank Eperjesi
    • 1
  • Hannah Bartlett
    • 1
  1. 1.Ophthalmic Research Group, School of Life and Health SciencesAston UniversityBirminghamUK

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