METHODS. Subjects consumed daily a formulation containing 10 mg L, 2 mg Z, and 10 mg MZ (active group; n ¼ 53) or placebo (n ¼ 52) for a period of 12 months. Study visits were at baseline, 3, 6, and 12 months. Contrast sensitivity at 6 cycles per degree (cpd) was the primary outcome measure (POM). Secondary outcome measures included CS at other spatial frequencies, best-corrected visual acuity (BCVA), glare disability, photostress recovery, and light scatter. Macular pigment optical density (MPOD) was measured using dual-wavelength autofluorescence, and serum carotenoid concentrations were analyzed using high performance liquid chromatography (HPLC).RESULTS. Compared to placebo, statistically significant improvements from baseline CS were detected at 6 (P ¼ 0.002) and 1.2 (P ¼ 0.004) cpd in the active group. Additionally, improvements in CS were commensurate with the observed increases in retinal concentrations of these carotenoids (r ¼ 0.342, P ¼ 0.002 at 6 cpd). CONCLUSIONS.These results indicate that dietary fortification with the macular carotenoids can have meaningful effects on visual function.

Antioxidant supplementation in patients with nonadvanced age-related macular degeneration results in significant increases in macular pigment and improvements in CS and other measures of visual function. (Clinical trial, http://www.isrctn.com/ISRCTN13894787).

We note the letter from Professors Richard Bone and John Landrum 1 in response to our recently published clinical trial entitled ''Enrichment of Macular Pigment Enhances Contrast Sensitivity in Subjects Free of Retinal Disease: Central Retinal Enrichment Supplementation Trials -Report 1'' 2 and we thank our colleagues for their positive comments on our study. We acknowledge also their concerns about our Figure 1, which was prepared and included in our manuscript to help with the description of what we know about the distribution of lutein, zeaxanthin, and meso-zeaxanthin at the macula, and, more importantly, what we have learned from interventional trials using the macular carotenoids.3 In other words, we believe our figure reflects the totality of available evidence. For example, we know that, in subjects with central dips (i.e., at 0.258 eccentricity) in their macular pigment, supplementation with a formulation containing meso-zeaxanthin (and not lutein) is required to rebuild their central macular pigment, 3 and this observation is important because it indicates that mesozeaxanthin is the candidate composite of central macular pigment.It is important to point out that Figure 1 in our manuscript does not claim to quantify the carotenoids at the macula, but rather showcase what we have learned regarding the relative distribution of the macular carotenoids. Also, and in reply to the main concern raised by Bone and Landrum in their letter, we do not feel that our figure presents ''L as an annular ring around the fovea.'' Review of Figure 1 and the accompanying legend suggests that lutein is also present in the central macula but is distributed further into the periphery, where mesozeaxanthin is not. The high concentration of meso-zeaxanthin presented centrally in our figure, and only centrally, may influence the interpretation of this figure, so it is important that it is clarified here, as per the explanation above. However, we do not doubt that there is room for improvement in our illustrative attempt, and we will take on board Bone and Landrum's comments in any further refinements of the Figure in question.Of course, the pioneering work by Bone and Landrum must also be acknowledged, as it informed all those working on macular pigment with respect to the distribution of the carotenoids at the macula.4,5 However, it is our view that additional work is needed, and across differing populations (e.g., healthy control eyes, eyes with AMD, eyes with Macular Telangiectasia) using the now sensitive and further developed HPLC methods available, to further understand the distribution of the carotenoids at the macula. This is particularly important because (unlike in 1997) we now know from the literature that the distribution of macular pigment is not as simple as originally proposed (i.e., it cannot just be described as a firstorder exponential decline with increasing retinal eccentricity) (Delori FC, et al. IOVS 2004;45:ARVO E-Abstract 1288).6-9 Also, careful review of the papers cited by Professors Bone and Landrum, sh...