Age-related Macular Degeneration (AMD)

Introduction

Age-related Macular Degeneration (AMD) is a disease which affects the macula and is defined as a maculopathy which affects people over the age of 50 and includes the presence of drusen and altered retinal pigment epithelium (RPE) pigmentation. Drusen are extracellular deposits of lipids, proteins, and cellular debris which are found within the layers of the retina and appear as small, yellow deposits on dilated eye exams.

The macula is the central region of the retina and is responsible for fine detailed vision and colour vision. AMD is part of the aging process, where metabolic waste products from the retina build up underneath the retina. These are normally removed in younger patients but accumulate in older patients and damages the sensitive retina at the macula. This leads to a slow and progressive thinning and degeneration of the photoreceptors and the RPE gradually leads to failure of central vision. The larger the drusen, the greater the area and the larger the areas of RPE change, the greater the risk of late AMD.

AMD is the leading cause of blindness in western countries and is responsible for two thirds of all sight impairment registrations in the UK. In 2006 it was estimated that 30-50 million people world-wide were affected, with the incidence increasing with age.¹ More recent studies show that the world-wide prevalence of AMD is expected to increase from 198 million in 2020 to 288 million in 2040.² There are 2 main types of AMD: Dry (non-exudative, non-neovascular) AMD and Wet (exudative, neovascular) AMD. Later stages of the disease are associated with impairment of vision.

Dry (non-exudative, non-neovascular) AMD²

Most common form (80%)
Slower progression, usually bilateral
Geographic atrophy (GA) is the advanced stage of dry AMD

Wet (exudative, neovascular) AMD

Less common than dry
More rapid progression to advanced sight loss
Main manifestations are choroidal neovascular membrane (CNVM) and pigment epithelium detachments (PED)

Approximately 90% of people with dry AMD will only have mild or moderate gradual visual loss and lifestyle measures (not smoking, taking a diet rich in dark green leafy vegetables, Omega 3, etc.) can slow its progression.³Although it is the less aggressive form, advanced late Dry AMD still causes about 20-25% of AMD related severe visual loss.

Wet (neovascular) AMD is caused by the growth of new vessels from the choroidal circulation. Hypoxia in the RPE leads to Vascular Endothelial Growth Factor (VEGF) being released, which causes new vessels to grow, in order to try and stabilize the nutrition and support of the RPE by the choroid. These vessels can leak or bleed, which causes disruption and damage to the macula through:

Sub-RPE fluid (Serous Pigment epithelium detachment)
Sub-retinal fluid
Intra-retinal fluid
Sub-retinal Hyperreflective material (SHRM)
Haemorrhages

The fluid usually causes distortion and rapid visual loss. In some early cases the vision can be preserved. The most extreme vision loss is usually due to large haemorrhages under the macula (sub macula haemorrhage). Wet AMD affects about 10-20% of those who have AMD. It is important to recognise it early as it is potentially treatable. However, if untreated it causes severe visual loss it is responsible for 90% of severe visual acuity loss from AMD.⁴

AMD has a profound effect on patient quality of life. A patient clinical study looking at dry AMD and its impact found most dry AMD patients suffer with difficulty driving, reading, completing activities of daily living, frustration, dependency on other people, stress and anxiety and lack of confidence.²

Macula. Image permission courtesy of Mr Mike Horler

Drusen deposits. Image permission courtesy of Mr Mike Horler

Sub retinal fluid (SRF) and a pigment epithelium detachment (PED) adjacent. Image permission courtesy of Mr Mike Horler

Clinical Evaluation

As laid out by the National Institute for Health and Care Excellence (NICE) guidelines the risk factors of AMD are:⁵

Older age
Presence of AMD in the other eye
Family history of AMD
Smoking
Hypertension
BMI of 30 kg/m2 or higher
Diet low in omega 3 and 6, vitamins, carotenoid and minerals
Diet high in fat
Lack of exercise

Other factors which are key to note are:⁶

Excessive light exposure
Hypercholesterolemia
Female gender
Light complexion
Light coloured irides

Symptoms & Signs of AMD (dry and wet):

	Dry AMD	Wet AMD
Symptoms	Early often asymptomatic Slower progression and more gradual reduced vision, usually bilateral but asymmetrical. Light to dark adaption difficulty Near vision affected (reading) May describe a significant change in vision if they go on to develop wet AMD Symptoms as taken from a study analysing patient effects of dry AMD in order of how many patients had these symptoms: – Blurred vision – Difficulty seeing in low-light environment – Progressive vision loss – Poor depth perception – Distorted vision – straight lines appearing wavy – Poor contract/things appear washed out – Poor light/dark adaptation – Light flashes/floaters – Loss of central visual field/central blind spot – Defective colour vision – Headache – Visual hallucinations (Charles Bonnett Syndrome) – Restricted visual fields	Complain of sudden onset reduced vision or distortion (Micropsia and macropsia) Some types of wet AMD can develop slowly over a few months Sometimes, patients aren’t aware of a drop in vision in the affected eye because the unaffected eye “masks” the effect, until they cover the good e.g at an eye exam
Signs	Drusen Pigmentary abnormalities o Hyperpigmentation o Hypopigmentation The disease classification depends on drusen size and number and other pigmentary changes in the macula. The Beckmann classifications use Normal ageing changes, Early AMD, intermediate AMD and late AMD (which includes advanced atrophic dry AMD and wet AMD).	Macula haemorrhages may cause distortion or acute visual symptoms Larger central haemorrhages can be intra retinal or sub macula and are likely to reduce the VA significantly Fluid associated with Wet AMD can be subretinal fluid (SRF) or intra retinal fluid (IRF)

People with many large soft drusen are more likely to develop atrophy and severe visual loss. The larger the drusen, the greater the area and the larger the areas of RPE change, the greater the risk of developing late AMD-wet AMD and advanced dry AMD.

Management & Advice

Dry AMD

Dry macular degeneration is managed through lifestyle changes, nutritional supplements, and monitoring. Patients are advised to stop smoking, adopt a nutrient-rich diet including the antioxidants vitamins C and E, zinc, copper, and lutein. The Age-Related Eye Disease Study 2 (AREDS2) also concluded that antioxidants supplements may be of benefit in certain patient groups. ^{3, 7-9}
Regular eye exams are crucial to detect changes. While there is no cure, certain therapies may slow progression.
Regular home self-monitoring with Amsler grid.
Low vision aids, like magnifying lenses, help improve daily functioning.
Emerging treatments, such as stem cell therapy and gene therapy are being explored in clinical trials and intravitreal treatments for slowing atrophy progression are licensed in some countries
Patients should consult their eye care professionals to tailor a personalised treatment plan and stay informed about advancements in managing dry macular degeneration.

Wet AMD

Wet macular degeneration demands a rapid intervention to prevent vision loss. The primary treatment is anti-VEGF (vascular endothelial growth factor) intravitreal injections, like bevacizumab (Avastin), ranibizumab (Lucentis), aflibercept (Eylea), and faricimab (Vabysmo) ^{5, 10-12} administered into the eye to inhibit abnormal blood vessel growth and leakage. These injections are typically repeated at regular intervals and have become the standard of care, with a large body of evidence to demonstrate their efficacy and safety. ¹³
Regular monitoring through optical coherence tomography (OCT) imaging tests is crucial to assess response and adjust treatment plans.
Some clinicians adopt a PRN/treat as required approach and inject once fluid is seen on scanning. More commonly now, most hospitals adopt a treat and extend approach. This is where patients are given a loading dose of 3 injections over the course of 2 months and then planned injections are given at set intervals and the interval is gradually extended between injections, as long as the OCT scans remain ‘dry’ or free of oedema. If Fluid reoccurs after an extension, the interval is then shortened until it becomes ‘dry” again.^14,15
Patients may also benefit from nutritional supplements like those used in dry macular degeneration treatment. If they have wet macular degeneration in one eye only and dry macular degeneration in the other eye. Patients should also consider lifestyle modifications such as stopping smoking and maintaining a healthy diet.
Early detection and swift action are paramount in managing wet macular degeneration. Collaborative efforts between patients and eye care professionals are essential to tailor treatment plans, address concerns, and adapt strategies to preserve vision and enhance the quality of life for individuals affected by this sight-threatening condition.

This article serves as an overview of the condition and treatment options. It does not serve as a clinical guidance. Eyecare provider guidelines should be used when managing patients.