No abstract

PurposeThe Central Retinal Enrichment Supplementation Trials (CREST) aim to investigate the potential impact of macular pigment (MP) enrichment, following supplementation with a formulation containing 10 mg lutein (L), 2 mg zeaxanthin (Z) and 10 mg meso-zeaxanthin (MZ), on visual function in normal subjects (Trial 1) and in subjects with early age-related macular degeneration (AMD; Trial 2).MethodsCREST is a single center, double-blind, randomized clinical trial. Trial 1 (12-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ and 2 mg Z (n = 60) or placebo (n = 60). Trial 2 (24-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ, 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention A; n = 75) or 10 mg L and 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention B; n = 75). Contrast sensitivity (CS) at 6 cycles per degree represents the primary outcome measure in each trial. Secondary outcomes include: CS at other spatial frequencies, MP, best-corrected visual acuity, glare disability, photostress recovery, light scatter, cognitive function, foveal architecture, serum carotenoid concentrations, and subjective visual function. For Trial 2, AMD morphology, reading speed and reading acuity are also being recorded.ConclusionsCREST is the first study to investigate the impact of supplementation with all three macular carotenoids in the context of a large, double-blind, randomized clinical trial.

The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the macula, where they are collectively referred to as macular pigment (MP). Augmentation of this pigment, typically achieved through diet and supplementation, enhances visual function and protects against progression of age-related macular degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a highly bioavailable matrix. In this single-blind placebo-controlled study, L- and MZ-enriched eggs and control non-enriched eggs were fed to human subjects (mean age 41 and 35 years, respectively) over an 8-week period, and outcome measures included MP, visual function and serum concentrations of carotenoids and cholesterol. Serum carotenoid concentrations increased significantly in control and enriched egg groups, but to a significantly greater extent in the enriched egg group (P<0·001 for L, Z and MZ). There was no significant increase in MP in either study group post intervention, and we saw no significant improvement in visual performance in either group. Total cholesterol increased significantly in each group, but it did not exceed the upper limit of the normative range (6·5 mmol/l). Therefore, carotenoid-enriched eggs may represent an effective dietary source of L, Z and MZ, reflected in significantly raised serum concentrations of these carotenoids, and consequentially improved bioavailability for capture by target tissues. However, benefits in terms of MP augmentation and /or improved visual performance were not realised over the 8-week study period, and a study of greater duration will be required to address these questions.

Macular pigment (MP) is composed of lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ). The present study reports on serum response to three different MP supplements in normal subjects (n 27) and in subjects with age-related macular degeneration (AMD) (n 27). Subjects were randomly assigned to: Group 1 (20 mg L and 2 mg Z), Group 2 (10 mg L, 2 mg Z and 10 mg MZ) or Group 3 (3 mg L, 2 mg Z and 17 mg MZ). Serum carotenoids were quantified at baseline, and at 4 and 8 weeks using HPLC. Response data for normal and AMD subjects were comparable and therefore combined for analysis. We report response as the average of the 4-and 8-week concentrations (saturation plateau). Serum L increased significantly in Group 1 (0·036 mmol/l per mg (269 %); P,0·001) and Group 2 (0·079 mmol/l per mg (340 %); P,0·001), with no significant change in Group 3 (0·006 mmol/l per mg (7 %); P¼0·466). Serum Z increased significantly in Group 1 (0·037 mmol/l per mg (69 %); P¼ 0·001) and Group 2 (0·015 mmol/l per mg (75 %); P,0·001), with no significant change in Group 3 (20·0002 mmol/l per mg (26 %); P¼0·384). Serum MZ increased significantly in Group 1 (0·0094 mmol/l (absolute value); P¼ 0·015), Group 2 (0·005 mmol/l per mg; P,0·001) and Group 3 (0·004 mmol/l per mg; P,0·001). The formulation containing all three macular carotenoids (Group 2 supplement) was the most efficacious in terms of achieving the highest combined concentration of the three MP constituent carotenoids in serum, thereby potentially optimising the bioavailability of these compounds for capture by the target tissue (retina).

Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Group mean (±sd) MFT reduced significantly from baseline (233 (±59)) to exit (205 (±40)) (P = 0.001). CDVA exhibited no change between baseline and exit visits (P = 0.48 and P = 0.31, resp.). Measures of visual function that did exhibit statistically significant improvements (P < 0.05 for all) included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS), mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition.