David Lally, MD: Geographic atrophy is considered the advanced stage of dry age-related macular degeneration (AMD), and dry AMD really has three stages. It starts as what we call the early stage and the hallmark feature of macular degeneration is the presence of drusen, so we see that in the early stage. Some patients will progress to the intermediate stage, which is the second stage of disease, where we can observe either larger size drusen and or the presence of pigment abnormalities in the retina. And from there, some patients will progress over time to the advanced dry stage called geographic atrophy. That is where we observe the sharply demarcated areas of atrophy in the macula. And specifically, we see death of the retinal pigment epithelial cells with the photoreceptors and the outer retina and the choriocapillaris.

These atrophic lesions of atrophy can develop in different locations, and in different patterns for different patients. Some patients will develop an area of geographic atrophy that develops in the center of the macula, in the fovea. Other patients will develop areas of atrophy that begin outside the very center of the retina, so we'd call the non-foveal region. Some patients develop one atrophic lesion over time, while other patients can develop multifocal lesions, meaning more than one area begins to develop geographic atrophy over time. We know that when these areas of atrophy develop, the natural history of these lesions is to expand over time and enlarge in their area over time.

Depending on where these lesions develop initially, will result in different symptoms that the patients will notice when they first arise. If a lesion develops within the fovea, then that's involving the center of the macula and typically those patients will start to complain of problems with their central vision, as that area of geographic atrophy appears. As that area expands over the years, the patients will notice a progressive, unrelenting decline in their central visual acuity that corresponds to the area of atrophy enlarging over time. This is different than a patient who would have a lesion that initially arises in the non foveal, non-central region of the macula. In those cases, when the lesion first arises, patients may not have any symptoms at all, and it might just be detected by the eye care provider. However, as that lesion grows and expands over the years, it typically enlarges and gets closer to the center of the fovea. And as it begins to encroach on the center of the fovea, the patients then will typically start to complain of problems with their central vision.

What are the main complaints we hear from patients with geographic atrophy? Well, the number one complaint we hear would be trouble with reading and tasks up close. They say when I'm reading, certain letters might be missing in the words I'm reading, or I might miss words all together in the line of a sentence. Patients might complain that I can still see the letters but they're kind of blurred and distorted, certain letters may be distorted. Other complaints we would hear besides reading issues would be trouble with driving. Patients will say I'm starting to have trouble seeing street signs and seeing the exit I need to get off of the road. So those are the two main complaints we hear with patients with geographic atrophy.

Now, as the lesions progress over the years, and they enlarge, eventually, the central visual acuity does become impacted significantly. And, and the progression of problems with vision can progress to a point where the patient someday says, I can no longer see the face of the person standing in front of me. When patients ask me, ‘what's the worst case scenario in the future for me with geographic atrophy?’ I tell them the absolute worst case with this disease is you're looking at somebody's face, and it's black. But you can see everything around the face. So macular degeneration never affects your peripheral vision, it can only affect your central vision. Patients often ask, what's the speed that I'm going to get to that point where I cannot see somebody's face? And the answer is that this is a highly variable disease in terms of its progression rates.

We talked that lesions can appear in different locations in the retina, they can appear in the center or off to the side, some patients have multifocal lesions, many lesions developing, others just have one. And depending on the pattern, and the progression rate, we can see that level of progression of the visual symptom deterioration over time, we can see it vary dramatically among patients. Some patients can lose significant vision in the course of a few years. Other patients, it can take a much longer time, until they have severe visual impairment. I think that's important for the audience to understand is that it's a very heterogeneous disease, with many different types of presentations. Typically, I tell patients, when I first see them, and I first diagnosed them with geographic atrophy. I don't know what their progression rate is going to be until I see them back in follow up examinations, and I get repeat imaging. I can start to understand what sorts of rates of progression I'm seeing in terms of the enlargements of those geographic atrophy lesions.

Once I follow that eye for a few years, I can then start to predict better for patients, what I anticipate happening to their vision in the future. In terms of risk factors for developing geographic atrophy, far and away the greatest risk factor is is the age of the patient. We know that the older you are, the greater the risk of developing atrophy. And that risk does not increase in a linear fashion, but it increases exponentially as you get older, over the age of 70 and 80 years old. There's something about aging, which we haven't figured out yet, that is the number one driving factor in the development of geographic atrophy.