Overview of Geographic Atrophy (GA)

Eleonora M. Lad, MD, PhD: Hello and welcome to this Peer Exchange titled, “Emerging Treatment Options for Geographic Atrophy.” I’m Dr Eleonora Lad; I’m a clinician scientist in medical retina and director of clinical research at Duke University School of Medicine in Durham, North Carolina. Joining me today in this virtual discussion are 3 of my colleagues. Would you please introduce yourselves?

David R. Lally, MD: Hello. I’m David Lally, and I’m the director of the Retina Research Institute at New England Retina Consultants, located in Springfield, Massachusetts.

Jayanth Sridhar, MD: I’m Dr Jay Sridhar; I’m an associate professor of clinical ophthalmology at the Bascom Palmer Eye Institute in Miami, Florida.

Nancy M. Holekamp, MD, FASRS: Hi, I’m Dr Nancy Holekamp. I am director of retina services at the Pepose Vision Institute in St. Louis, Missouri.

Eleonora M. Lad, MD, PhD: Thank you. Today we’re going to discuss geographic atrophy [GA] and its great clinical burden to the patient and families. We‘ll also discuss current management and emerging treatment options for geographic atrophy, and the promise of newer therapies that are being offered for this condition. Let’s get started on our first topic. David, would you please discuss the progression of age-related macular degeneration over time, leading to development of geographic atrophy?

David R. Lally, MD: Macular degeneration has multiple stages. The hallmark feature of the earliest stage of macular degeneration is the presence of drusen, which are these deposits or waste material build-up under the retina that’s associated with aging. Over time some patients will progress to the intermediate stage of the disease, where we start to see larger sized drusen and/or the presence of pigment abnormalities in the retina. From there, some patients will progress to the late form of the disease, which is characterized by either the presence of what we call geographic atrophy, or the development of neovascularization of the retina, called wet macular degeneration.

Eleonora M. Lad, MD, PhD: Nancy, what are the risk factors for developing geographic atrophy?

Nancy M. Holekamp, MD, FASRS: The major risk factor is of course, age. I don’t want to overlook that because when we look at the clinical trials for geographic atrophy, the median age is about 77; that’s much later than the median age for clinical trials for wet macular degeneration, which is in the early 70s, or even our diabetic clinical trials, which would be in the 60s. The No. 1 risk factor is age. In my clinical practice I find that people struggle with vision in their early to mid-80s, so age is the number 1 risk factor. We also know it has a strong genetic component, and again in clinical practice, when you see patients with GA, they’ll mention that their parent had it, or a sibling has it, and it tends to run in the family. The genetics are not Mendelian, it’s not autosomal dominant or recessive, it’s polygenic; it’s a complex inherited disease, where multiple different DNA variations come together to create this inherited risk for age-related macular degeneration and the advanced form, which is GA.

Eleonora M. Lad, MD, PhD: Excellent. Jay, as a retina specialist, what anatomical changes are seen in the patients with geographic atrophy on your exam?

Jayanth Sridhar, MD: That’s a fantastic question. One of the first things we start to see is the loss of the retinal and RP [retinitis pigmentosa] architecture, as well as the prominence of the choroidal vessels that are underlying. They’re always there, but we don’t see them with the same prominence. As you see these areas vary, the geographic term comes from the map-like distribution of these areas where you have that prominence of the choroidal vessels. That ties into some of the findings when you do the more sophisticated imaging besides the exam.

Eleonora M. Lad, MD, PhD: Speaking of which, David, please tell us about imaging modalities used for the diagnosis of geographic atrophy.

David R. Lally, MD: Historically, we had fundus photography as the gold standard for imaging geographic atrophy, where we see these atrophic, well-demarcated lesions in the macula that can be either in the center, foveal, or nonfoveal region. Sometimes there are multifocal lesions, and we see loss of the RPE [retinal pigment epithelium]. There’s a window defect where you can clearly visualize the underlying choroidal vasculature. Over time, there’s been an explosion of new technology in imaging, it’s a very exciting part of our field. We now have what we call fundus autofluorescence, where we can measure the fluorescence levels of some of the lipofuscin pigments that are located in the RPE cells and in the outer retinal cells, and that’s been very helpful for our clinical trials. Recently, we’ve had a consortium group come up with a new definition for defining atrophy-related macular degeneration based on OCT imaging, or optical coherence tomography imaging. This might be the future, in terms of diagnosing, managing, and following these diseases, as we think this instrument may be the most sensitive tool for following the disease.

Transcript edited for clarity