Macular pigment response to lutein, zeaxanthin and meso-zeaxanthin supplementation in open angle glaucoma: a randomized controlled trial

Abstract Purpose To evaluate the macular pigment response to carotenoid supplementation in glaucomatous eyes. Design A double masked, randomized and placebo-controlled clinical trial, the European Nutrition In Glaucoma Management (ENIGMA) study ( ClinicalTrials.gov Identifier: NCT04460365). Participants Sixty-two participants (38 male, 24 female) with a diagnosis of open-angle glaucoma were enrolled in this trial. Forty-two were randomized to receive the active supplement, while 20 participants were allocated to placebo. Methods Macular pigment optical density (MPOD) was measured by autofluorescence using the Heidelberg Spectralis confocal scanning laser ophthalmoscope. MPOD volume within the central 6° of retinal eccentricity as well as MPOD at 0.23, 0.51, 0.74 and 1.02 degrees retinal eccentricity were recorded at baseline and at six-monthly intervals over 18-months. Visual function was assessed using visual acuity, mesopic and photopic contrast sensitivity under glare conditions, photostress recovery time, microperimetry and glaucoma activities limitation (GAL-9) questionnaire. Advanced glaucoma module scans of retinal nerve fiber layer thickness and ganglion cell complex thickness over the central six degrees of retinal eccentricity were also completed at each study visit. Main Outcome Measures Change in MPOD following supplementation with 10mg lutein, 2 mg zeaxanthin and 10mg meso-zeaxanthin or placebo over 18 months. Results A mixed model repeated measures ANOVA analysis revealed a statistically significant increase in MPOD volume during the study period (significant time effect - F(3,111)=89.31, MSE=1656.9, 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 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.