Correlations Between Macular, Skin, and Serum Carotenoids

Abstract

PurposeOcular 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.MethodsEighty-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.ResultsSkin 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.ConclusionsLarger 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.

What do we know about the macular pigment in AMD: the past, the present, and the future

“…Groups have argued that visual axis opacities such as cataracts may alter measurements; however, we did not find a significant 'cataract effect' on volume measurements [71,76]. The technique is also highly reproducible even in the face of significant ocular pathology such as exudative AMD and diabetic macular edema [71]. Unfortunately, dual wavelength autofluorescence is not perfect either, as it requires pupillary dilation and expensive equipment to obtain the measurements.…”

“…7), we have found that volumetric measurements appear to be superior to previously used optical densities in regards to their correlative power with other carotenoid measurement techniques [71]. Groups have argued that visual axis opacities such as cataracts may alter measurements; however, we did not find a significant 'cataract effect' on volume measurements [71,76]. The technique is also highly reproducible even in the face of significant ocular pathology such as exudative AMD and diabetic macular edema [71].…”

“…From the findings of large epidemiological studies and AREDS2 that found a reduced risk of AMD progressing to advanced form with higher carotenoid consumption, groups became interested in attempting to quantify macular pigment concentrations to identify patients at risk of developing AMD [10,62,68]. Several measurement modalities have been proposed and have been compared elsewhere [71]. The use of high-performance liquid chromatography (HPLC) is the gold standard analytical method to measure MP within the eye, but it is tissue destructive, time-consuming, and provides little-to-no spatial distribution information [18].…”

“…There has been concern that these methods maybe affected by visual axis opacities (e.g., cataract) and are quite expensive to manufacture [61]. Fortunately, most of these methods have been shown to correlate with other previously mentioned techniques including HFP [71,75]. There has been notable measurement discordance between HFP and reflectometry-based techniques [75].…”

“…Unfortunately, HPLC requires time-consuming extractions and analyses, and prior attempts at using dietary assessments have shown that they are both tedious and fraught with recall errors and bias. While skin Raman spectroscopy can be easily performed, it cannot readily differentiate various carotenoids and requires specialized equipment; it correlates well with HPLC total serum, biopsied skin tissue, and volumetric concentrations obtained by dual wavelength autofluorescence [71]. While there are numerous techniques available to quantify MP both invasively and non-invasively, each technique is hindered by either its availability, cost of production, and/or expertise in implementation.…”