Macular pigment imaging in AREDS2 participants: an ancillary study of AREDS2 subjects enrolled at the Moran Eye Center

Abstract

Purpose: Age-Related Eye Disease Study 2 (AREDS2) is a randomized, placebo-controlled study designed to determine whether supplementation with 10 mg of lutein and 2 mg of zeaxanthin per day can slow the rate of progression of age-related macular degeneration (AMD). Although some biomarkers of response to carotenoid supplementation such as serum concentrations are part of the AREDS2 protocol, measurement of carotenoid concentrations in the eye and other tissues is not. In this approved ancillary study, macular pigment optical density (MPOD), macular pigment distributions, and skin carotenoid levels at enrollment and at each annual visit were measured to assess baseline carotenoid status and to monitor response to assigned interventions.

Methods: All subjects enrolled at the Moran Eye Center had MPOD and macular pigment spatial distributions measured by dual-wavelength autofluorescence imaging and total skin carotenoids measured by resonance Raman spectroscopy. Results. Baseline MPOD in enrolled subjects was unusually high relative to an age-matched control group that did not consume carotenoid supplements regularly, consistent with the high rate of habitual lutein and zeaxanthin consumption in Utah AREDS2 subjects prior to enrollment. MPOD did not correlate with serum or skin carotenoid measurements.

Conclusions: Useful information is provided through this ancillary study on the ocular carotenoid status of AREDS2 participants in the target tissue of lutein and zeaxanthin supplementation: The macula. When treatment assignments are unmasked at the conclusion of the study, unique tissue-based insights will be provided on the progression of AMD in response to long-term, high-dose carotenoid supplementation versus diet alone. (ClinicalTrials.gov number, NCT00345176.).

Conflict of interest statement

Disclosure: P.S. Bernstein, None; F. Ahmed, None; A. Liu, None; S. Allman, None; X. Sheng, None; M. Sharifzadeh, None; I. Ermakov, None; W. Gellermann, None

Figures

Figure 1

  Examples of macular pigment autofluorescence images obtained from AREDS2 participants. Most subjects have radially symmetric patterns, but a few have very low MP levels with fragmented distributions (scale is expanded 3-fold for clarity for fragmented distribution).

Figure 2

  Correlation of peak macular pigment optical density (MPOD) in right and left eyes of subjects who had both eyes measured by autofluorescence imaging (AFI) (n = 33; r = 0.9206; P < 0.0001).

Figure 3

  MP spatial distributions in normal and AREDS2 subjects. In the top panel we show examples of five different radially symmetric patterns seen when performing autofluorescence imaging: Category (A) has very low MP levels (peak MPOD <0.05). (B) Enhanced central MP levels and lower eccentric levels. (C) Has only a sharp, central MP distribution. (D) Has a central MP concentration surrounded by lower amounts arranged as a ring or shoulder. (E) Has both central and parafoveal MP levels. Bottom left panel is the MP distribution in a normal population.Bottom right panel is the MP distribution in the Moran Eye Center AREDS2 population.

Figure 4

  Peak MPOD versus age in the study population. The solid line is the regression line of peak MPOD versus age (n = 44; r = −0.2268; P = 0.1388). The dashed lines denote the mean ± SD of an age-matched unsupplemented control population measured with the same instrumentation.

Figure 5

  Skin Raman counts versus age in the study population. The solid line is the regression line of skin Raman counts versus age (n = 50; r = 0.1758; P = 0.2219). The dashed lines denote the mean ± SD of a normal unsupplemented control population measured with the same instrumentation.

Figure 6

  Skin Raman counts versus total serum carotenoids (top panel: n = 45; r = 0.4727; P = 0.0010) and serum lutein + zeaxanthin (bottom panel: n = 45; r = 0.1843; P = 0.2256) in the study population.

Figure 7

  Peak MPOD versus total serum carotenoids (top panel: n = 41; r = −0.1436; P = 0.3705) and serum lutein + zeaxanthin (bottom panel: n = 41; r = 0.0261; P = 0.8714).

Figure 8

  Skin Raman counts versus peak MPOD in the study population (n = 44; r = −0.0167; P = 0.9144).