Correlations Between Macular, Skin, and Serum Carotenoids

Christopher D Conrady, James P Bell, Brian M Besch, Aruna Gorusupudi, Kelliann Farnsworth, Igor Ermakov, Mohsen Sharifzadeh, Maia Ermakova, Werner Gellermann, Paul S Bernstein, Christopher D Conrady, James P Bell, Brian M Besch, Aruna Gorusupudi, Kelliann Farnsworth, Igor Ermakov, Mohsen Sharifzadeh, Maia Ermakova, Werner Gellermann, Paul S Bernstein

Abstract

Purpose: Ocular and systemic measurement and imaging of the macular carotenoids lutein and zeaxanthin have been employed extensively as potential biomarkers of AMD risk. In this study, we systematically compare dual wavelength retinal autofluorescence imaging (AFI) of macular pigment with skin resonance Raman spectroscopy (RRS) and serum carotenoid levels in a clinic-based population.

Methods: Eighty-eight patients were recruited from retina and general ophthalmology practices from a tertiary referral center and excluded only if they did not have all three modalities tested, had a diagnosis of macular telangiectasia (MacTel) or Stargardt disease, or had poor AFI image quality. Skin, macular, and serum carotenoid levels were measured by RRS, AFI, and HPLC, respectively.

Results: Skin RRS measurements and serum zeaxanthin concentrations correlated most strongly with AFI macular pigment volume under the curve (MPVUC) measurements up to 9° eccentricity relative to MPVUC or rotationally averaged macular pigment optical density (MPOD) measurements at smaller eccentricities. These measurements were reproducible and not significantly affected by cataracts. We also found that these techniques could readily identify subjects taking oral carotenoid-containing supplements.

Conclusions: Larger macular pigment volume AFI and skin RRS measurements are noninvasive, objective, and reliable methods to assess ocular and systemic carotenoid levels. They are an attractive alternative to psychophysical and optical methods that measure MPOD at a limited number of eccentricities. Consequently, skin RRS and MPVUC at 9° are both reasonable biomarkers of macular carotenoid status that could be readily adapted to research and clinical settings.

Figures

Figure 1
Figure 1
Macular pigment tracing from a healthy subject. (a) Macular pigment tracing at 0.5° (red), 2° (blue), and 9° (green) demarcated by the solid lines as indicated. (b) Macular pigment image showing the fovea and the degrees (0.5°, red; 2°, blue; 9°, green) from the center of the macula lutea.
Figure 2
Figure 2
Extremes of macular pigment. A vitamin A–deficient subject (a) was compared with a healthy subject not taking any carotenoid supplements (b) and a patient consuming an excessive amount of carotenoids from her diet and supplements (c) to emphasize differences in MPOD and MPVUC measurements at various eccentricities as indicated in (d).
Figure 3
Figure 3
Reproducibility of RRS and macular pigment and the effect of cataracts. (a, b) MPOD at 0.5° (red) and MPVUC at 2° (blue) and 9° (green) were followed over a year period in two individuals with independent recordings for each eye plotted. The readings showed very consistent results over time and between eyes. (c) Another patient had repeat measurements of skin carotenoids over a 6-month time-period and were relatively consistent as well. (d) Four patients underwent macular pigment evaluation pre- and postcataract surgery. The percent change between these two measurements is shown with MPOD at 0.5° and MPVUC at 0.5°, 2°, and 9°. Red points, MPOD at 0.5°; Blue points, MPVUC at 2°; Green points, MPVUC at 9°.
Figure 4
Figure 4
Comparison of macular pigment and serum zeaxanthin. Linear regression analyses of serum zeaxanthin with (a) MPOD at 0.5° (r = 0.411, P < 0.0001), or (b) MPOD at 2° (r = 0.480, P < 0.0001). (c) Macular pigment volume under the curve at 0.5° (r = 0.394, P = 0.0001), (d) MPVUC at 2° (r = 0.484, P < 0.0001), and (e) MPVUC at 9° (r = 0.614, P < 0.0001). All serum concentrations of carotenoids are in nanograms per milliliter in (a–e).
Figure 5
Figure 5
Comparison of skin RRS and serum carotenoid concentrations. Resonance Raman spectroscopy was compared with (a) total serum carotenoids (r = 0.722, P < 0.0001) and (b) lutein (r = 0.655, P < 0.0001), (c) zeaxanthin (r = 0.656, P < 0.0001), and (d) lutein + zeaxanthin (r = 0.664, P < 0.0001). All serum concentrations of carotenoids are in nanograms per milliliter in (a–d).
Figure 6
Figure 6
Comparison of skin RRS and macular pigment. Resonance Raman spectroscopy was compared with (a) MPOD at 0.5° (r = 0.445, P < 0.0001) and (b) 2° (r = 0.629, P < 0.0001) and (c) MPVUC at 0.5° (r = 0.406, P < 0.0001), and (d) 2° (r = 0.565, P < 0.0001), and (e) 9° (r = 0.663, P < 0.0001).
Figure 7
Figure 7
Effect of oral supplementation on skin, serum, and macular carotenoids. (a, b) Linear regression plots of MPVUC 9° and skin RRS were plotted against serum lutein + zeaxanthin concentrations. (c) Skin RRS and MPVUC 9° were then compared. Red data points represent those patients reporting daily consumption of supplements containing >0.5 mg of lutein and/or zeaxanthin. Blue lines delineate the empirically defined borders between normal and supranormal measurements. Serum carotenoid concentrations are in nanograms per milliliters.

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