AMD is a painless condition and people with the early and intermediate stages of the condition do not usually experience any symptoms. Regular (annual/biennial) eye examinations are recommended in order to detect the early signs of AMD. These examinations also allow the detection of other eye diseases, many of which may also be painless and without obvious symptoms in their early stages (e.g. glaucoma).

Definitive diagnosis of AMD relies on a dilated eye examination using imaging techniques typically undertaken in specialist ophthalmology clinics. It is important to note that visual acuity tests (reading letters on a chart) alone are not sufficient for the detection of AMD. This is because sight measured by the visual acuity test can remain unaffected, even in the presence of nAMD or GA, if the central part of the retina is not affected by the condition. Therefore, it is essential that any person suspected of having AMD is referred to a specialist clinic for accurate diagnosis and follow-up.

Several retinal imaging techniques may be used by the ophthalmologist to diagnose and monitor patients with AMD in clinical practice. These non-invasive imaging techniques include Colour Fundus Photography (CFP), Fundus Auto-Fluorescence (FAF), Fluorescein Angiography, Optical Coherence Tomography (OCT) and a very new technique called OCT angiography.

AMD pathology is characterized by degenerative changes in the outer portion of the retina, photoreceptors, retinal pigment epithelium (RPE), Bruch’s membrane, and the choriocapillaris, which ultimately lead to central vision loss in the later stages of the disease. The earliest visible sign of AMD during an eye exam is the appearance of yellowish deposits of an extracellular lipoprotein, called drusen, which accumulate underneath the retina, between the retinal pigment epithelium (RPE) and Bruch’s membrane.¹

Progression and severity of AMD can be classified as ‘early’ or ‘intermediate’ or ‘late’ based on the size of drusen and the presence of pigmentary abnormalities in the retina of the affected eye.⁴

Early AMD is diagnosed based on the presence of medium-sized drusen (>63 and ≤125 μm), but is not usually associated with any loss of visual function or other symptoms. (Small drusen particles (≤63 μm) can appear in the retina as part of the normal aging process, and are not associated with an increased risk of progression to late-stage AMD.)

Intermediate AMD is characterised by the presence of large drusen (>125 μm), abnormalities in the retinal pigment, or both. Intermediate AMD also tends to be asymptomatic. People who develop intermediate AMD are at an increased risk of developing late-stage AMD.

Late-AMD, associated with central vision loss that occurs as a result of damage to the macula, can be classified into two types: ⁴

Geographic atrophy (GA) (also known as ‘dry’ or ‘non-exudative’ AMD) ) is characterised by the progressive, irreversible loss of the retinal pigment epithelium (RPE), photoreceptor cells, and underlying choriocapillaris layer of the macula, resulting in a decline in visual function.

Neovascular AMD (also known as ‘wet’ or ‘exudative’ AMD) is defined by growth and invasion of immature blood vessels from the underlying choroid into the retina. Leakage from these fragile blood vessels can cause build-up of blood and fluid under the retina leading to detachment of the RPE or retina and scarring.

Progression from early/intermediate- to late- AMD (GA and/or neovascular AMD) is a complex process. Some people progress quickly to late-stage AMD (either GA or neovascular AMD), whereas others may progress slowly over several years.⁵ The underlying mechanisms that cause an eye to develop GA versus neovascular AMD are not fully understood. No reliable genetic or environmental risk factors have been identified to predict whether a patient will develop one form or the other.⁶ Both types can occur simultaneously in the same eye, or simultaneously in different eyes; it has in fact been suggested that GA and neovascular AMD are not mutually exclusive diseases, but that they lie on the same disease continuum.⁷ Eyes developing both types may in fact be at a more advanced stage than either GA or neovascular AMD alone.

Access the full bibliography here.

Early and Intermediate AMD

People with early and intermediate stages of AMD do not usually experience symptoms. Therefore, it is very important that regular eye examinations are performed in order to detect the early signs of AMD. These examinations also allow the detection of other eye diseases, many of which may also be painless and without obvious symptoms in their early stages (e.g. glaucoma).

Late-stage AMD (GA and nAMD)

Common symptoms relating to vision deterioration reported by people with late-stage AMD, either geographic atrophy (GA) or neovascular AMD (nAMD) include:

Blurring of central vision/Loss of visual acuity (gradual or rapid onset) – reduced ability to see in detail (e.g. greater difficulty reading small print in newspaper or a reduction in reading rate). Tends to occur gradually in persons with GA but can be rapid in people with nAMD; this can affect one or both eyes. GA and nAMD may occur alone, separately in each eye or simultaneously in the same eye.

Metamorphopsia – A type of distorted vision where straight lines in a grid appear wavy; this is a common symptom among people who have neovascular AMD. (The Amsler Grid is a useful tool for monitoring your central visual field and testing metamorphopsia.)

Blind spots (scotomas) in the central field of vision – an area of partial alteration in the field of vision consisting of a partially diminished or entirely degenerated visual acuity that is surrounded by a field of normal – or relatively well-preserved vision.

Reduced contrast sensitivity – difficulty seeing an image against a ‘similar’ background.

Delayed dark adaptation – difficulty adjusting when moving from bright to dimly lit environments.

Access the full bibliography here.

Early & Intermediate AMD

While there are no therapies to completely cure AMD there are a few therapies that have demonstrated promising results in clinical trials that aim to slow progression of intermediate AMD to sight threatening advanced stages such as Geographic Atrophy and nAMD. Antioxidant and mineral supplementation have been shown to reduce the risk of progression of early & intermediate AMD to late AMD (AREDS & AREDS2).​¹⁰​ Supplements containing vitamins C & E, zinc & copper and lutein & zeaxanthin are recommended. Similarly, light-based therapies also known and photobiomodulation such as Valeda Light Delivery system have recently demonstrated encouraging results. ​¹¹​

Late AMD

Geographic Atrophy (GA) – Two FDA approved therapies (Pegcetacoplan and avacincaptad pegol) are available in the US with none currently available in Europe.​¹²​Both these therapies aim to slow down the progression of GA to advanced stages and hence delay sight loss. A recent study that conducted a post hoc analysis of the Age-Related Eye Disease Study (AREDS) studies showed that the AREDS supplements slow progression of disease in late GA also and may be a potential therapeutic option.​¹³​

Neovascular AMD – Photodynamic Therapy and Laser photocoagulation for neovascular AMD have been available since the 1990s. However, more recently anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized the treatment of neovascular AMD.  Anti-VEGF treatments are a group of medicines which reduce new blood vessel growth or oedema (swelling). There are a number of licensed anti-VEGF treatments on the market bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab. These therapies are administered by intravitreal injection and research is ongoing to improved drug delivery and reducing the frequency of the dose with innovative solutions such as ocular implants for sustained drug delivery and one time gene therapies.​¹⁴

Access the full bibliography here.

AMD results from a combination of environmental and genetic factors. Environmental factors associated with AMD include age, gender, smoking and diet. Evidence for genetic risk has also been supported by several family studies and twin studies. Results from these studies revealed that people with an affected parent have approximately twice the risk of getting AMD than someone whose parent does not have AMD.

DNA is the chemical in our cells that gives our bodies instructions about how to grow, develop and function. DNA is a string of coded messages organised into specific instructions called genes. Humans have 30,000 different genes, arranged on a number of thread-like structures, called chromosomes. We inherit our chromosomes from our parents, 23 from our mother and 23 from our father, so we have two sets of 23 chromosomes, or 23 ‘pairs’. A good description is If you think of genetics as the book of life, then the DNA are the letters, the genes are words, and the chromosomes are the chapters.

If you think of a mutation as a spelling mistake or a series of words changed in a sentence, then this causes a problem in the meaning and interpretation, and it is just this that happens when there is a mistake or a mutation occurs in a gene – it can cause a condition like inherited AMD.
Sometimes a mutation will have no effect at all. This depends on environmental factors, an element of chance, or mutations in other genes. Mutations can cause problems if they stop the gene or chromosome communicating the correct instructions needed for the body to function properly.

In the largest study of the complete set of human genes to date, it was reported that AMD is associated with a number of types of mutations, 45 common single nucleotide polymorphisms (SNPs) and 7 rare variants across 34 genetic loci, which explain 34% of AMD risk​³​. Many of these genetic variants reside in the complement factor H (CFH) gene on chromosome 1 and ARMS2/HTRA genes on chromosome 10. Other variants can be seen in and around genes involved in the cholesterol metabolism, collagen production and cell signalling. This suggests that AMD is a complex disease associated with multiple genetic risk factors​⁴​.

Access the full bibliography here.