What it is
The age-related macular degeneration (AMD) is, in industrialised countries, the major cause of severe and irreversible visual impairment in people over the age of 65. It is a condition that affects the central portion of the retina, the macula, responsible for clear vision. AMD occurs when the portions of the retina responsible for the nutrition of the rods and cones and for the elimination of metabolic products lose their effectiveness in carrying out these functions due to ageing. Consequently, the photoreceptors deteriorate and die, causing the loss of vision in the central part of the visual field, the macula, more delicate and sensitive, while leaving peripheral vision intact.
In most cases it is a progressive disease that often affects both eyes, usually one eye being affected within a few years from the other. The anatomical site in which the pathological events that characterise AMD are developed is represented by the external retina-choriocapillary complex.
Types of AMD
There are two different forms of this condition: Dry (non-exudative or atrophic): All age-related macular degenerations begin as a dry form. About 85% of people with age-related macular degeneration only show the dry form. Wet (exudative or neovascular): The wet form occurs in about 15% of subjects. Although only 15% of patients with age-related macular degeneration show the wet form, 80 to 90% of cases of severe vision loss in patients with age-related macular degeneration are related to the wet form. The dry form of age-related macular degeneration causes changes in the retinal pigment epithelium, typically seen as dark, pin point areas. The retinal pigment epithelium plays a vital role in keeping rods and cones healthy and well-functioning. The accumulation of waste products from cones and rods can lead to the formation of drusen, visible as yellow spots. Areas of chorioretinal atrophy (referred to as geographic atrophy) occur in more advanced cases of the dry form of age-related macular degeneration. There are no signs of macular scar thickening (disciform scar) nor of oedema, haemorrhage or exudation.
The wet form of age-related macular degeneration occurs when new abnormal blood vessels are developed under the retina in a process called choroidal neovascularisation (abnormal formation of new vessels). Focal macular oedema or haemorrhage can cause an elevation of a macular area or a localised detachment of the retinal pigment epithelium. Finally, untreated neovascularisation results in a submacular disciform scar.
The currently known risk factors, in addition to ageing, are the following: cigarette smoking (3 times greater risk than non-smokers), family history (4 times greater risk in relatives of subjects affected by the disease), sex (higher prevalence in women), race and ethnicity (higher prevalence in whites), refractive error (for each dioptre of hypermetropia there is a 5% increased risk of developing AMD), iris colour (eyes with dark irises rich in melanin and therefore well pigmented seem more protected from light-induced oxidative damage), cataract (subjects with a history of cataract surgery have a statistically significant risk of progression or development of advanced AMD), arterial hypertension, alcohol consumption, exposure to sunlight. Recent studies have shown a correlation between the vitamin D level (serum quantity of 25(OH)D) and the risk of early or late AMD.
In atrophic (dry) age-related macular degeneration, loss of central vision occurs over the years and is painless; the majority of patients maintain sufficient vision for reading and driving. Areas of central blindness (scotomas) usually occur late during the disease and can sometimes become severe. Symptoms are usually bilateral. Ocular fundus changes include: changes in the retinal pigment epithelium; drusen; areas of chorioretinal atrophy.
Rapid loss of visual function, usually over days or weeks, is more typical of the wet form. The first symptom is usually visual distortion, such as a central area of blindness (scotoma) or curvature of straight lines (metamorphopsia). Peripheral vision and colour vision are generally not impaired; however, the patient can become legally blind in the affected eye, especially if age-related macular degeneration is not treated. Exudative age-related macular degeneration usually affects one eye at a time. Ocular fundus changes include: subretinal oedema which appears as focal thickening of the retina, retinal oedema, gray-green discoloration under the macula, exudates in or around the macula, detachment of the retinal pigment epithelium (visible as an area of retinal thickening), subretinal haemorrhage in or around the macula.
Ocular fundus examination
Ocular fundus colour photograph
Optical coherence tomography
Both forms of age-related macular degeneration are diagnosed by fundus examination. Changes in the visual function can often be detected with an Amsler grid. Colour photography and fluorescein angiography are done when the findings suggest the exudative form. Angiography shows and characterises the subretinal choroidal neovascular membranes and makes it possible to delimit the areas of geographical atrophy. Optical coherence tomography (OCT) is useful in identifying intraretinal or subretinal oedemas and may help assess the response to treatment.
Prevention Prevention undoubtedly represents the first step in the treatment of macular pathologies. The AREDS (Age-Related Eye Disease Study) and AREDS 2 (Age-Related Eye Disease Study 2) studies have highlighted the efficacy of using high doses of antioxidants and zinc to reduce the risk of progression towards the advanced form in patients affected by AMD with drusen in both eyes or advanced AMD in one eye only.
Antiangiogenic therapy, for some years now there has been an increasing use of antiangiogenic drugs in the treatment of the wet form. These drugs act by inhibiting the VEGF (Vascular Endotelial Growth Factor), the growth factor at the base of the development of the new vessels responsible for the most advanced and aggressive forms of the disease, thus preventing their growth.
Photodynamic therapy, among the first therapies born for the treatment of neovascular AMD, still used today only in some and particular forms of neovascularisation. This method is based on the selective destruction of the walls of the newly formed vessel through the photochemical activation of a substance injected at a systemic level, Verteporfin.
Photocoagulative thermal laser therapy, used only for the treatment of some forms of macular degeneration, intended only for cases in which the lesion appears localised outside the central portion of the macula (extrafoveal neovascularisation).