**2. The macula and retina**

The macula is the central part of the retina, the neurosensory portion of the eye, and it is responsible for detailed central and colour vision due to its high concentration of cone photoreceptors. Anatomically, the macula is centred on the foveola, and has a ganglion cell layer of more than one cell in thickness. The macula has a diameter of approximately 5.5 mm. The macula is characterised by a yellowish colour (hence the term *macula lutea*, which is Latin for 'yellow spot'), attributable to the presence of macular pigment (MP).[1] The concentration of MP peaks at the centre of the macula, where the appearance of the 'yellow spot' may be clearly evident on clinical examination or fundus photography [Figure 1]. MP is optically undetectable outside the macula.[2] Within the layer structure of the retina, the highest concentration of MP is seen in the receptor axon layer and the inner plexiform layer.[1]

The retina consists of a neurosensory portion comprised of nine individual layers, and an external retinal pigment epithelium (RPE). The RPE plays an important physiological role in the maintenance of neurosensory retinal health, through functions including Vitamin A metabolism, phagocytosis of photoreceptor outer segments, maintenance of the outer bloodretina barrier, heat exchange, and the active transport of substances in and out of the RPE.[3] The blood supply of the retina is derived from the inner retinal vasculature and the outer choriocapillaris. Non-pathological changes that occur in the RPE with age include an

increase in cellular pleomorphism and a decrease in cell number, with migration of peripheral RPE cells towards the macula, reduced melanin composition, and an accumulation of the age-pigment lipofuscin.[4;5] These changes may lead to a reduction in the metabolic activity of the RPE, with subsequent apoptosis, which pre-dates pathological change.[5;6] The RPE is separated from the choriocapillaris by Bruch's membrane (BrM). BrM is a semipermeable filtration barrier, comprised of five individual layers.[7;8] Disruption of BrM may result in alteration of its filtration properties, impacting on the function of the RPE and the neurosensory retina.[9] Changes that occur in BrM with age include an increase in its overall thickness, with a reconfiguration of associated lipids and proteins and the accumulation of debris.[10;11] When this debris accumulates between BrM and the RPE, it is referred to as a basal laminar deposit (BlamD) and is not specifically pathological in nature.[12] However, when deposits accumulate within the inner collagenous layer of BrM, they are referred to as basal linear deposits (BlinDs) and are a histopathological hallmark of AMD.[13] These deposits (BlamDs and BlinDs) contain a wide range of constituents including collagen, inflammatory proteins and lipoproteins. When sufficient debris accumulates in BlinDs, they are visible clinically as drusen.[14;15]

#### **3. Age-related macular degeneration**

Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 years of age in the developed world, and it results in loss of central and colour vision if not treated, or if not amenable to treatment.[16-18] The loss of central vision impacts greatly on the individual, as their ability to perform simple daily tasks, such as reading, watching television, driving and recognizing people's faces becomes increasingly difficult. Thus, their quality of life and their ability to lead an independent life diminish significantly as the disease progresses. The peripheral retina is not affected in individuals with AMD, regardless of stage, such that, in the absence of other ocular pathology, peripheral (navigational) vision remains unchanged.

It is currently estimated that late AMD affects 513,000 people in the United Kingdom (2.4% of those over the age of 50), and that this number will increase to 679,000 by the year 2020.[19] Prevalence data from the United States in 2004 estimated that more than 1.75 million individuals were affected by the disease, with this latter figure expected to rise to almost 3 million by the year 2020.[20] The prevalence of this condition is likely to increase dramatically in the future, as a result of increasing life-expectancy and the resultant increasing senescence of society.[21] Data from the National Eye Institute in the United States in 2004 indicated that the prevalence of advanced AMD in people over 40 years of age was 1.47%, rising to 15% in white females aged over 80 years. Beyond its impact on the individual sufferer,[22] the predicted increase in longevity (Figure 2), coupled with the predicted growth in world population (Figure 3) will significantly increase the socio-economic burden that AMD places on countries and their health-care systems.[23-26]

they are visible clinically as drusen.[14;15]

(navigational) vision remains unchanged.

systems.[23-26]

**3. Age-related macular degeneration** 

increase in cellular pleomorphism and a decrease in cell number, with migration of peripheral RPE cells towards the macula, reduced melanin composition, and an accumulation of the age-pigment lipofuscin.[4;5] These changes may lead to a reduction in the metabolic activity of the RPE, with subsequent apoptosis, which pre-dates pathological change.[5;6] The RPE is separated from the choriocapillaris by Bruch's membrane (BrM). BrM is a semipermeable filtration barrier, comprised of five individual layers.[7;8] Disruption of BrM may result in alteration of its filtration properties, impacting on the function of the RPE and the neurosensory retina.[9] Changes that occur in BrM with age include an increase in its overall thickness, with a reconfiguration of associated lipids and proteins and the accumulation of debris.[10;11] When this debris accumulates between BrM and the RPE, it is referred to as a basal laminar deposit (BlamD) and is not specifically pathological in nature.[12] However, when deposits accumulate within the inner collagenous layer of BrM, they are referred to as basal linear deposits (BlinDs) and are a histopathological hallmark of AMD.[13] These deposits (BlamDs and BlinDs) contain a wide range of constituents including collagen, inflammatory proteins and lipoproteins. When sufficient debris accumulates in BlinDs,

Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 years of age in the developed world, and it results in loss of central and colour vision if not treated, or if not amenable to treatment.[16-18] The loss of central vision impacts greatly on the individual, as their ability to perform simple daily tasks, such as reading, watching television, driving and recognizing people's faces becomes increasingly difficult. Thus, their quality of life and their ability to lead an independent life diminish significantly as the disease progresses. The peripheral retina is not affected in individuals with AMD, regardless of stage, such that, in the absence of other ocular pathology, peripheral

It is currently estimated that late AMD affects 513,000 people in the United Kingdom (2.4% of those over the age of 50), and that this number will increase to 679,000 by the year 2020.[19] Prevalence data from the United States in 2004 estimated that more than 1.75 million individuals were affected by the disease, with this latter figure expected to rise to almost 3 million by the year 2020.[20] The prevalence of this condition is likely to increase dramatically in the future, as a result of increasing life-expectancy and the resultant increasing senescence of society.[21] Data from the National Eye Institute in the United States in 2004 indicated that the prevalence of advanced AMD in people over 40 years of age was 1.47%, rising to 15% in white females aged over 80 years. Beyond its impact on the individual sufferer,[22] the predicted increase in longevity (Figure 2), coupled with the predicted growth in world population (Figure 3) will significantly increase the socio-economic burden that AMD places on countries and their health-care

**Figure 1.** Colour fundus photograph showing the macula, surrounding the fovea, which is centred on the foveola (not marked, but evident as the 'yellow spot') of a left eye.
