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Research into Age-related Macular Degeneration

Types and Stages of Macular Degeneration

Types of Macular Degeneration

There are two types of age-related macular degeneration (AMD), commonly referred to as “dry” or “wet.” They are named for the kinds of physical changes that affect the retina, and in particular the macula, the central area of the retina which gives us our visual acuity, color vision and ability to perceive contrast. 

All AMD starts as the dry form, which may progress from early to intermediate and advanced stages, the last of which is called geographic atrophy. 

In 10 – 15% of patients with dry AMD, the disease converts to the wet form, which is also an advanced form of AMD. The conversion to wet AMD can occur at any stage of dry AMD, but is more likely in the intermediate and advanced stages.  In wet AMD, faulty blood vessels grow and leak fluid behind the retina, causing sudden, dramatic visual distortion and irreversible vision loss.  

Patients may have dry AMD, wet AMD, or both at the same time, in either or both eyes.  This may sound confusing, but the dry and wet forms of AMD are not mutually exclusive, which means that the dry form may continue to progress in an eye that has developed the wet form, and vice versa.

Many patients report that they were first diagnosed as having wet AMD.  If you noticed changes in your vision, went to an eye care specialist, and received a diagnosis of wet AMD, that means that your dry AMD was undetected — usually because people don’t start seeing an eye doctor until there are problems — and transformed into wet.  

This is why it is important to learn the risk factors for AMD — especially family history, a history of smoking, obesity and poor diet — and to schedule regular eye exams, starting as early as 40 years of age, if you are at increased risk.

Click here to learn more about the risk factors for AMD.


Dry AMD is a broad term that covers all forms of AMD that are not wet AMD.  In dry AMD, waste material, generated by the intense metabolic activity of photoreceptors in the retina, accumulates behind the macula and forms deposits called drusen.  In older people, having some, smaller drusen is considered normal, but in a person with AMD the body’s waste removal system cannot adequately remove this material, and over time the drusen increase in number and size. 

Drusen are made of fats combined with proteins (much like the plaque that line blood vessels in cardiovascular disease), and they hinder the absorption of nutrients that normally are delivered to the photoreceptors by the capillary-rich tissue of the retina called the retinal pigmented epithelium (RPE).  With less access to necessary nutrients, photoreceptors start to die, which leads to reduced visual acuity, color vision and also to a loss of contrast sensitivity.  When drusen become larger, they can physically push photoreceptors out of their normal position, which can create distortion that causes straight lines to appear wavy.  When enough photoreceptors die, a dead zone appears in our central visual field.

According to the American Academy of Ophthalmology, drusen are not the underlying cause of AMD, but the presence of a significant number of large, soft drusen is a sign of dry AMD. 

Dry AMD is also referred to as atrophic AMD because it causes a thinning — or atrophy — of the macula.  Non-exudative AMD is another term for dry AMD, which simply means that it is not wet (exudative) AMD.

While no treatments currently are available for dry AMD, several are in clinical trials and may soon reach patients.  Until then, the best way to manage dry AMD is to slow its progression by making risk-reducing lifestyle choices: stop smoking, eat an AMD-beneficial diet, maintain proper weight and blood pressure, exercise, and protect your eyes from the damaging light of the sun.

Learn more about Dry Macular Degeneration.


Progression to the wet form of AMD happens in about 10-15% of AMD patients. It is called “wet” due to the development of leaky blood vessels that have grown to compensate for the functional problems created by the dry form of AMD.  The excessive growth of these leaky blood vessels is called neovascularization, which is why wet AMD is also called neovascular AMD, or nAMD for short.

Treatments exist for wet AMD that can stop the development of leaky blood vessels by interfering with the body’s signaling for new blood vessel growth.  These treatments require injections into the eye of drugs called anti-VEGF agents, at regular intervals that you establish with your eye doctor. Over time, based on how you respond to the treatments, your retina specialist may suggest that the time between them can be extended.  A new class of treatments, that combine anti-VEGF agents with agents that also reduce leakage from existing blood vessels, is becoming available.

While treatments for wet AMD are designed to preserve current sight and prevent further vision loss, some patients can experience improved visual acuity as fluids that have leaked behind the retina are reabsorbed and the macula resumes its normal position.

The transition to wet AMD can be sudden, accompanied by dramatic central vision loss.  This can be avoided to a great extent if you work closely with your eye care specialist to monitor the progression of your dry AMD (both at home, using self-testing tools, and through regular office visits) and report any changes to your vision right away. The same holds true for monitoring your wet AMD and not missing treatment appointments, which can allow the disease to progress.

Learn more about Wet Macular Degeneration.

Stages of macular degeneration

There are four stages of AMD, defined by physical and/or functional changes to the retina, the macula, and underlying structures.   

Sub-clinical AMD — Loss of Dark Adaptation

Studies have shown that, several years before drusen are detectable, cholesterol deposits build up between the RPE and photoreceptors, interfering with nutrient transport, causing some photoreceptors to die.  Since drusen are not clinically detectable at this stage (or are so small that they are not considered an indicator of AMD), this stage is referred to as sub-clinical.

This earliest stage of AMD can precede the development of drusen by several years and is characterized by a diminished ability of our eyes to adjust from a bright surrounding to a darker surrounding.  It’s called loss of dark adaptation, and it happens to some degree to everyone as we age. In a person with AMD, however, it can occur at a much earlier age and can be more pronounced.  

Cataracts can cause symptoms that also impair night vision. So, if you are aware that AMD runs in your family, and you are starting to have difficulty seeing at night, or driving at night against the lights of oncoming traffic, or reading in dim light, you may want to have your eyes tested for loss of dark adaptation as early as your 40s.

Early AMD — Drusen of medium size

Early dry AMD is usually asymptomatic and is often diagnosed at a routine dilated eye exam based on the discovery of the presence of medium sized drusen.  Loss of dark adaptation may accelerate at this stage.

Intermediate AMD — Large Drusen

AMD is considered at the intermediate stage if large drusen are detected and/or your doctor detects any retinal pigment abnormalities. Changes in retinal pigment occur as we age, but are accelerated in AMD. 

For some patients, this stage may still be asymptomatic, but many patients experience diminished contrast sensitivity or a blurred spot in their central vision.  These changes could lead to visual distortions, blurred type when reading, a sense that colors are no longer as vibrant as they used to be, and difficulty seeing in low light conditions.

At this stage of the disease, an eye care specialist may recommend that a patient starts to use a nutritional supplement, called the AREDS2 formula, to potentially slow the progression of AMD. Some eye care specialists recommend this supplement even earlier in the course of AMD.

Click here to learn more about AMD nutrition.

Advanced or Late AMD — Geographic Atrophy and/or Wet AMD

At this stage patients begin to experience definitive central vision loss. In addition to the presence of large drusen that may fuse with other drusen, enough photoreceptors have died to cause vision loss. Damage can be due to the development of geographic atrophy (the dry form of advanced AMD) or the onset of neovascular AMD (the wet form of advanced AMD). 

Wet AMD has been discussed, above.

Geographic Atrophy (GA)

Geographic atrophy (also called atrophic AMD) is an advanced form of dry AMD that affects more than 5 million people worldwide and accounts for 20% of all legal blindness attributed to AMD.  According to studies, its development is driven approximately 70% by genetics, and 30% by aging and environmental stressors (including those caused by smoking, poor diet and sun exposure).  

GA is diagnosed at an ophthalmologist’s office, based on imaging taken during a dilated pupil exam, when large, clearly defined areas of the retina have lost pigment and photoreceptors have died.  These lesions represent areas of irreversible vision loss.

Recent studies of GA indicate that AMD patients with early or intermediate AMD progress to GA at a much higher rate than had previously been known, and if you have GA in one eye the likelihood of developing it in the other eye is even higher.   Up to 19% of AMD patients may progress to GA within approximately 2 years of diagnosis with early or intermediate AMD.

As mentioned earlier, having wet AMD does not prevent the development of GA, or vice versa: within approximately 2 years of developing wet AMD, up to 37% of patients develop GA; within approximately 2 years of developing GA, up to 29% of patients develop wet AMD.

While there are no currently available treatments for dry AMD, including for GA, several drugs for GA are entering late-stage clinical trials. These drugs are designed to slow the growth of GA lesions, whose size is connected to reduced functional vision.  For example, while studies have shown that 2 out of every 3 GA patients lose the ability to drive in under 2 years following their GA diagnosis, these emerging treatments may extend GA patients’ ability to drive, along with other quality-of-life activities, such as reading and the ability to perform household chores.

With more information emerging about GA, AMD patients should familiarize themselves with its impact on quality of life and steps they can take to counter that impact.