An investigation into the spatial profile of macular pigment

INTRODUCTION The macula is the central region of the retina and is responsible for sharpest visual acuity. At the center of the macula, the carotenoids lutein (L), zeaxanthin (Z), and meso-Z, are concentrated, where they are collectively referred to as macular pigment (MP). MP acts as a filter of short-wavelength (blue) light and is a powerful antioxidant. Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. AMD is believed to be caused by cumulative and chronic insult from reactive oxygen intermediates (ROIs), which are mainly generated from oxygen metabolism and short-wavelength (blue) light exposure. MP is believed to protect against AMD due to its short-wavelength (blue) light filtering and antioxidant properties. OBJECTIVES This PhD thesis was designed to: 1) Investigate the reproducibility of the MP spatial profile using customised heterochromatic flicker photometry (cHFP), and to relate the MP spatial profile to foveal architecture (Study One). 2) Investigate the relationship between specific MP spatial profile types and risk factors for AMD (Study Two). 3) Investigate if weight loss is associated with changes in serum concentrations of L and Z, and/or macular pigment optical density (MPOD) (Study Three). METHODS Study One: The Spatial Profile of Macular Pigment and its Relationship with Foveal Architecture We recruited 16 healthy subjects (nine had the typical exponential MP spatial profile [Group 1]; seven had a secondary peak MP spatial profile [Group 2]). MP spatial xxv profile was measured using cHFP on three separate occasions. Six radiance measurements were obtained at each locus (0.25º, 0.5º, 1º, and 1.75º eccentricity; reference point: 7º). Foveal architecture was assessed by optical coherence tomography (OCT). Study Two: The Spatial Profile of Macular Pigment and its Relationship with Risk Factors for AMD The MP spatial profile of 484 healthy subjects was measured using cHFP and categorised into one of two profile types (typical exponential or atypical ‘central dip’). Data on risk factors for AMD were obtained using a general health and lifestyle questionnaire. Dietary intake of L and Z were assessed using a validated food frequency questionnaire (FFQ). Serum concentrations of L and Z were also assessed using high performance liquid chromatography (HPLC). Study Three: Changes in MPOD and serum concentrations of L and Z in response to weight loss We recruited 104 overweight subjects into this randomised-controlled weight loss study. For the intervention group (I group, n = 54), weight was assessed weekly and body composition, including body fat (kg and percentage body fat) were assessed at baseline, six and 12 months using dual energy x-ray absorbtiometry (DEXA). Weight loss was encouraged using dietary and exercise programmes. MPOD was measured by cHFP and serum concentrations of L and Z by HPLC (at baseline, one, three, six and 12- months). The control group (C group, n = 50) were assessed at baseline and 12-months. RESULTS Study One: The Spatial Profile of Macular Pigment and its Relationship with Foveal Architecture Subjects who had the typical decline profile still had this profile after averaging repeated measures (Group 1). Subjects who had a secondary peak displayed the secondary peak after averaging repeated measures (Group 2). Mean SD foveal width, Group 1 was significantly narrower than mean SD foveal width, Group 2 (1306 ± 240 xxvi µm and 1915 ± 161 µm, respectively; p < 0.01). This difference remained after controlling for sex (p < 0.001). Foveal width was significantly related to mean foveal MP, controlling for sex (r = 0.588, p = 0.021). Foveal profile slope was significantly related to MP spatial profile slope, following removal of an outlier (r = 0.591, p = 0.020). Study Two: The Spatial Profile of Macular Pigment and its Relationship with Risk Factors for AMD The presence of the ‘central dip’ MP spatial profile was significantly more common in older subjects (p = 0.004) and in current cigarette smokers, (p = 0.031). Also, there was a significant age-related decline in central MPOD (0.25° retinal eccentricity), but in males only (r = -0.146, p = 0.049). Study Three: Changes in MPOD and serum concentrations of L and Z in response to weight loss Repeated measures analysis of variance (RM ANOVA) demonstrated significant weight loss in the I group over the study period (p = 0.000). There was no significant weight change in the C group (p = 0.993). RM ANOVA of dietary L and Z, serum L and Z, and MPOD demonstrated no significant time, or time/group interaction, effect in any of these parameters (p > 0.05, for all), with the exception of a significant decrease in dietary intake of Z seen in both groups, over the study period (p < 0.05). There was a positive and significant relationship between body fat loss (kg) and increase in serum concentrations of L in the I group (r = 0.521, p = 0.006). CONCLUSIONS Study One: The Spatial Profile of Macular Pigment and its Relationship with Foveal Architecture Customised HFP reproducibly measures MP spatial profile. Secondary peaks seen in the MP spatial profile cannot be attributed to measurement error, and are associated with wider foveas. The slope of an individual’s MP spatial profile is related to foveal slope, with a steeper MP distribution seen with a steeper foveal depression. xxvii Study Two: The Spatial Profile of Macular Pigment and its Relationship with Risk Factors for AMD A ‘central dip’ in the MP spatial profile, seen in older subjects, and in cigarette smokers, is likely to be an undesirable feature of macular pigmentation, and one which may reflect increased risk of AMD. Further research is needed in this area. Study Three: Changes in MPOD and serum concentrations of L and Z in response to weight loss Our finding that a reduction in body composition (e.g. fat mass) is related to increases in serum concentrations of L is consistent with the hypothesis that body fat acts as a reservoir for this carotenoid, and that weight loss can positively influence circulating carotenoid levels.