Macular pigment and its contribution to visual performance in the older human eye A thesis submitted to the University of Manchester for the degree of a Doctor of Philosophy in the Faculty of Life Sciences 2014 Laura Patryas Optometry Contents 1 Introduction 19 1.1 Impact of ageing on the anatomy and physiology of the visual system . 20 1.1.1 The pupil . 22 1.1.2 The crystalline lens . 23 1.1.3 The retina . 24 1.1.4 Rods and cones . 26 1.1.5 Retinal pigment epithelium . 28 1.1.6 The interphotoreceptor matrix . 29 1.1.7 Bruch’s membrane . 30 1.1.8 Choriocapillaris and choroid . 30 1.2 Psychophysical function in ageing . 31 1.2.1 Spatial vision . 31 1.2.1.1 Visual acuity . 31 1.2.1.2 Contrast sensitivity . 32 1.2.2 Temporal vision . 33 1.2.3 Visual adaptation . 33 1.2.3.1 Dark adaptation . 33 1.2.3.2 Glare recovery . 36 1.3 Environmental factors in ageing . 37 1.3.1 Smoking . 38 1.3.2 Alcohol . 39 1.3.3 Radiation exposure . 39 1.3.4 Physical activity . 41 1.4 Ageing and age-related macular degeneration . 41 2 The macular pigment 43 2.1 Bio- and stereochemistry of macular pigment . 43 2.2 Location of macular pigment . 44 2 2.3 The function of macular pigment . 46 2.3.1 The potential role of macular pigment in normal healthy eyes . 49 2.4 Characteristics of macular pigment . 50 2.4.1 Composition . 50 2.4.2 Distribution . 50 2.4.3 Spatial profile . 52 2.4.4 Density and assimilation . 53 2.5 Factors affecting macular pigment density . 54 2.5.1 Age . 54 2.5.2 Gender . 54 2.5.3 Ocular factors . 55 2.5.3.1 Iris pigmentation . 55 2.5.3.2 Crystalline lens optical density . 55 2.5.4 Non-ocular factors . 55 2.5.4.1 Nutrition . 55 2.5.4.2 Smoking . 58 2.5.4.3 Obesity . 58 2.5.4.4 Light exposure . 58 2.5.4.5 Heredity . 59 2.5.4.6 Cultural differences in nutrition . 59 2.5.4.7 Ethnicity . 59 2.6 From plant to supplement . 59 2.6.1 Xanthophyll extraction . 59 2.6.2 Supplement preparation . 60 2.6.3 Recommended dosage . 60 2.6.4 Supplement safety . 60 2.7 Nutritional augmentation of macular pigment . 61 2.7.1 Supplementation studies in healthy eyes . 61 2.7.1.1 Effect on visual function . 62 3 2.7.2 Supplementation studies in ocular disease . 65 2.8 Bioavailability of macular pigment . 68 2.8.1 Dietary factors . 68 2.8.2 Supplement type . 69 2.8.3 Non-dietary factors . 69 2.9 Measurement of macular pigment . 71 3 Development of methods 73 3.1 Dark adaptation . 73 3.1.1 Introduction . 73 3.1.1.1 Retinal disease and dark adaptation . 76 3.1.1.2 General health and dark adaptation . 77 3.1.1.3 Photochemistry . 79 3.1.2 Study apparatus . 82 3.1.3 Calculating the percentage bleach . 83 3.1.4 Procedure . 84 3.1.5 Correcting data for pre-retinal absorption . 86 3.1.6 Modeling of dark adaptation data . 87 3.2 Factors affecting dark adaptation parameters: experimental data . 89 3.2.1 Bleach intensity . 89 3.2.2 Bleach frequency . 91 3.2.3 Pupil dilation . 92 3.2.4 Flash position . 94 3.2.5 Stimulus size in the periphery: rod spatial summation . 95 3.2.6 Stimulus location . 97 3.2.7 Summary . 98 3.3 Macular pigment apparatus . 99 3.3.1 Procedure . 99 3.3.2 MPOD calculation . 101 4 3.3.3 Repeatability . 102 3.4 Study design and protocol . 102 3.4.1 Pilot study . 102 3.4.1.1 Study design . 102 3.4.1.2 Study protocol . 103 3.4.1.3 Objectives . 103 3.4.1.4 Selection of study population . 103 3.4.1.5 Inclusion criteria . 103 3.4.1.6 Exclusion criteria . 104 3.4.1.7 Ethical conduct of the study . 105 3.4.1.8 Patient information sheet . 105 3.4.1.9 Study procedure and visit schedule . 106 3.4.1.10 Statistical analysis . 106 3.4.2 Supplementation study . 106 3.4.2.1 Study design . 106 3.4.2.2 Study protocol . 107 3.4.2.3 Objectives . 107 3.4.2.4 Selection of study population . 107 3.4.2.5 Inclusion criteria . 108 3.4.2.6 Exclusion criteria . 108 3.4.2.7 Ethical conduct of the study . 109 3.4.2.8 Patient information sheet . 109 3.4.2.9 Study procedure and visit schedule . 109 3.4.2.10 Study formulation and randomisation . 110 3.4.2.11 Active and placebo tablet formulation . 111 3.4.2.12 Dispensation and randomisation . 113 3.4.2.13 Directions for use . 113 3.4.2.14 Compliance . 113 3.4.2.15 Sample size calculation . 114 3.4.2.16 Statistical analysis . 115 3.4.2.17 Study protocol alterations . 115 5 4 Assessment of age changes and repeatability for computer based rod dark adaptation 116 4.1 Abstract . 117 4.1.1 Purpose............................... 117 4.1.2 Methods.............................. 117 4.1.3 Results............................... 117 4.1.4 Conclusions............................. 117 4.2 Introduction . 118 4.3 Methods . 119 4.3.1 Subjects . 119 4.3.2 Procedure . 120 4.3.3 Data analysis . 122 4.4 Results . 123 4.4.1 Preliminary data . 123 4.4.2 Repeatability . 124 4.4.3 Dark adaptation in older and younger eyes . 125 4.5 Discussion . 127 4.6 References . 129 5 The association between dark adaptation and macular pigment optical density in healthy subjects 132 5.1 Abstract . 133 5.1.1 Purpose . 133 5.1.2 Methods . 133 5.1.3 Results . 133 5.1.4 Conclusions . ..