Macular Pigment Response to Lutein, Zeaxanthin, and Meso-zeaxanthin Supplementation in Open-Angle Glaucoma: A Randomized Controlled Trial

James Loughman, Ekaterina Loskutova, John S Butler, We Fong Siah, Colm O'Brien, James Loughman, Ekaterina Loskutova, John S Butler, We Fong Siah, Colm O'Brien

Abstract

Purpose: To evaluate macular pigment response to carotenoid supplementation in glaucomatous eyes.

Design: Double-masked, randomized, placebo-controlled clinical trial, the European Nutrition in Glaucoma Management Study (ClinicalTrials.gov identifier, NCT04460365).

Participants: Sixty-two participants (38 men, 24 women) with a diagnosis of open-angle glaucoma were enrolled. Forty-two were randomized to receive the active supplement, 20 participants were allocated to placebo.

Methods: Macular pigment optical density (MPOD) was measured by autofluorescence using the Heidelberg Spectralis scanning laser ophthalmoscope. Macular pigment optical density volume within the central 6° of retinal eccentricity as well as MPOD at 0.23°, 0.51°, 0.74°, and 1.02° were recorded at baseline and at 6-month intervals over 18 months. Visual function was assessed using visual acuity, mesopic and photopic contrast sensitivity under glare conditions, photo stress recovery time, microperimetry, and Glaucoma Activities Limitation 9 questionnaire. Advanced glaucoma module scans of retinal nerve fiber layer thickness and ganglion cell complex thickness over the central 6° of retinal eccentricity also were completed at each study visit.

Main outcome measures: Change in MPOD after supplementation with 10 mg lutein, 2 mg zeaxanthin, and 10 mg meso-zeaxanthin or placebo over 18 months.

Results: A mixed-model repeated measures analysis of variance revealed a statistically significant increase in MPOD volume (significant time effect: F(3,111) = 89.31, mean square error (MSE) = 1656.9; P < 0.01). Post hoc t tests revealed a significant difference in MPOD volume at each study visit for the treatment group (P < 0.01 for all), but no change in the placebo group (P > 0.05 for all). A statistically significant increase in mesopic contrast sensitivity under glare conditions was noted at 18 months in the treatment group, but not placebo. No other structural or functional changes were observed. No serious adverse events were noted during the trial.

Conclusions: Macular pigment can be augmented in glaucomatous eyes by supplementation with a formulation containing the carotenoids lutein, zeaxanthin, and meso-zeaxanthin. The greatest relative benefit was observed in those with the lowest baseline levels, but increases were noted across all participants and each retinal eccentricity. The potential benefits of MP augmentation for macular health in glaucoma merit further long-term evaluation.

Keywords: AMD, age-related macular degeneration; BMI, body mass index; CAREDS, Carotenoids in Age-Related Eye Disease Study; CS, contrast sensitivity; CSg, contrast sensitivity under glare; ENIGMA, European Nutrition in Glaucoma Management; GAL-9, Glaucoma Activities Limitation 9 questionnaire; GCC, ganglion cell complex; Glaucoma; HVF, Humphrey visual field; LZQ, Lutein and Zeaxanthin Questionnaire; Lutein; MD, mean deviation; MMSE, Mini-Mental State Examination; MP, macular pigment; MPOD; MPOD, macular pigment optical density; MSE, mean square error; Macular carotenoids; Macular pigment; Meso-zeaxanthin; OAG, open-angle glaucoma; RGC, retinal ganglion cell; RNFL, retinal nerve fiber layer; VA, visual acuity; VAR, visual acuity rating; Zeaxanthin; cpd, cycles per degree; dB, decibel; logCS, logarithm of contrast sensitivity units.

© 2021 by the American Academy of Ophthalmology.

Figures

Figure 1
Figure 1
Consolidated Standards of Reporting Trials flow diagram illustrating participant progress through the European Nutrition in Glaucoma Management trial. M = months.
Figure 2
Figure 2
A, Boxplot of macular pigment optical density (MPOD) volume illustrating MPOD values for the carotenoid treatment group (red) and the placebo group (green) for the baseline period (0m), 6 months (6m), 12 months (12m), and 18 months. Dots represent individual participant values at each time point. B, Line graph illustrating individual MPOD change for each participant in the active treatment group (left panel) and placebo treatment group (right panel).
Figure 3
Figure 3
Graph showing change in macular pigment optical density (MPOD) across retinal eccentricity (Ecc) in the carotenoid treatment group (upper) and placebo group (lower) over time. Error bars represent standard error of mean.
Figure 4
Figure 4
Scatterplot showing the percent change of macular pigment optical density (MPOD) volume after 18 months of carotenoid supplementation (treatment group) as a function of baseline MPOD volume.
Figure 5
Figure 5
Graph showing the change in mesopic contrast sensitivity (CS) under glare conditions during an 18-month period of supplementation with macular carotenoids (lutein 10 mg, zeaxanthin 2 mg, and meso-zeaxanthin 10 mg) or placebo. Data are presented as mean CS at each spatial frequency. Error bars represent standard error of the mean. cpd = cycles per degree.

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