About Age related macular
degeneration (AMD)

Advanced dry AMD and Geographic Atrophy (GA) are the same terms used to describe the advanced form of dry age-related macular degeneration (AMD), which is a leading cause of blindness worldwide.^1,2

Age-related macular degeneration (AMD) is a disease of the macula, the point of sharpest vision at the back of the eye. It is one of the most common causes of serious vision loss in western industrialised countries. One quarter of Europeans over the age of 60 are affected by AMD, be it early, intermediate or late-stage AMD.⁷

The macula and what happens when it ages

The macula has the highest density of photoreceptors. These are light-sensitive cells that convert light stimuli reaching the retina into electrical signals.¹²

The large number and density of photoreceptors enables the high resolution of this specialised part of the retina. Objects that we focus on are projected there, the image signals are converted into electrical impulses and transmitted to the brain through the optic nerve.¹²

Over our lifetime, light with its high energy affects the macula. The light is processed and transmitted by the photoreceptors, and this process produces waste products.¹¹ These waste products must be removed in a timely manner in order not to disrupt the visual process. This workload is not without its effects on the tissue. Over the years, fat-like substances, so-called drusen, accumulate. The drusen develop because the cells responsible for removing them can no longer do it quickly enough. Drusen are deposited under the photoreceptors, causing them to degrade and die over time. When this occurs, it is called Age-related Macular Degeneration (AMD).¹³

Most people are affected by early or intermediate AMD, but approximately 2% of those with AMD are affected by advanced AMD which is discussed in the next sections.

There are two forms of advanced age-related macular degeneration: Dry and Wet⁸

There are various eye disorders affecting the macula at the back of the eye, the central region of the retina. They are referred collectively as «macular degeneration». Since this eye disease mainly affects people over 65, it is also called age-related macular degeneration, in short, AMD.

Advanced AMD which includes both advanced dry AMD and wet AMD is considered the single largest cause of blindness in industrial nations.¹

About 40% of cases are advanced dry AMD, while 60% are wet AMD.⁷

Around 5 million people worldwide are affected by the advanced form of dry AMD.⁹

Advanced dry AMD and wet AMD are different manifestations of advanced AMD. An eye with advanced dry AMD can also naturally develop wet AMD, and vice versa.¹⁷

Next video: Advanced forms of Age-related macular degeneration

In the retina, millions of photoreceptors (light- sensitive cells) and other nerve cells transform light beams into electrical impulses that are sent to the visual cortex of the brain to make us see, what we see.¹²

Next video: How the vision works

A closer look at advanced dry AMD

The most predictive and central feature of developing advanced dry AMD is larger or confluent (flowing or merging) drusen as over 95% of patients with these features develop advanced dry AMD.¹³

Drusen are key features relevant for classification systems to grade the disease of AMD based on their presence and severity.¹⁷

In advanced dry AMD blind spots usually first appear outside of the central field of vision. As the disease progresses the central field of vision is affected and this ultimately leads to blindness.⁵ Advanced dry AMD is also called Geographic Atrophy. The name Geographic Atrophy refers to regions of atrophy, the blind spots, that look like a map to the examining doctor, hence this term.¹⁰

The stages of advanced dry AMD or Geographic Atrophy

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While lesion growth in advanced dry AMD may appear to proceed slowly, disease progression is often constant and irreversible.⁹

What the patient may see:
As the drusen in the retina get bigger and more numerous, they might dim or distort the vision, especially when reading. As the condition gets worse, the light-sensitive cells in the macula get thinner and eventually die. As the disease progresses, blind spots in the centre of the vision may occur and lead to the loss of central vision.

A closer look at wet AMD

Wet or neovascular AMD is the other advanced form of AMD. Wet AMD is the most common and more aggressive form of advanced AMD. It is responsible for most severe visual impairments in patients with advanced AMD, up to and including total loss of central vision.

What happens in wet AMD?

The main difference between dry AMD and wet AMD is how they affect the macula. Whereas dry AMD is associated with thinning and drying out of the macula, the wet type of macular degeneration produces the growth of abnormal blood vessels under the retina and the macula. These new blood vessels may then bleed and leak fluid, causing the macula to bulge or lift up from its normally flat position, thus distorting or destroying central vision. Under these circumstances, vision loss may be rapid and severe.

Unlike advanced dry AMD or GA, there are treatments available for wet AMD.

What the patient may see:
Blood vessels grow from underneath the macula. These blood vessels may leak blood and fluid into the retina. The vision is distorted so that straight lines look wavy. Also blind spots and loss of central vision may occur. Eventually, these blood vessels and their bleeding can form a scar, leading to permanent loss of central vision.

Helpful resources & links

References:

1. Gehrs KM, et al. Ann Med. 2006;38(7):450-471.
2. Fleckenstein, M. et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology 125, 369–390 (2018).
3. Sivaprasad S, et al. Ophthalmol Ther. 2019;8:115-124
4. Kaszubski P, et al. Ophthalmic Res. 2016;55(4):185-193
5. Boyer, D. S., Schmidt-Erfurth, U., Van Lookeren Campagne, M., Henry, E. C. & Brittain, C. The pathophysiology of geographic atrophy secondary to age-related macular degeneration and the complement pathway as a therapeutic target. Retina 37, 819–835 (2017).
6. Young, R. W. Pathophysiology of age-related macular degeneration. Surv. Ophthalmol. 31, (1987).
7. EURETINA. Retinal Diseases in Europe. PDF file. Accessed Apr. 29, 2021.
   https://www.euretina.org/downloads/EURETINA_Retinal_Diseases.pdf
8. Age-Related Macular Degeneration: Facts & Figures. Bright Focus Foundation. Accessed Apr. 29, 2021. https://www.brightfocus.org/macular/article/age-related-macular-facts-figures
9. Wong WL, et al. Lancet Glob Health. 2014;2:e106-116.
10. What is Geographic Atrophy? Bright Focus Foundation. Accessed Apr. 29, 2021. https://www.brightfocus.org/macular/article/what-geographic-atrophy
11. Ardeljan, D. & Chan, C. C. Aging is not a disease: Distinguishing age-related macular degeneration from aging. Progress in Retinal and Eye Research (2013) doi:10.1016/j.preteyeres.2013.07.003.
12. Bear, M., Connors, B. & Paradiso, M. Neuroscience: Exploring the Brain (Third Edition). Library (Lond). (2006) doi:10.1007/BF02234670.
13. Bonnel, S., Mohand-Said, S. & Sahel, J. A. The aging of the retina. Exp. Gerontol. (2003) doi:10.1016/S0531-5565(03)00093-7.
14. Pennington, K. L. & DeAngelis, M. M. Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. Eye Vis. 3, (2016).
15. Patel PJ, et al. Clin Ophthalmol. 2020;15-28

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