Biomarkers in Geographic Atrophy

David Lally, MD: Historically speaking, we have not had good therapies to treat geographic atrophy. The reason we have not had these good therapies is traditionally in our interventional clinical trials, we use visual acuity as our endpoint, as our measuring stick to determine if a treatment we're using has any effect of helping the patient with disease. We've learned over the years that visual acuity is a poor endpoint for studying geographic atrophy. And that's because this disease is a heterogeneous disease.

If a patient has a non-foveal geographic atrophy lesion, that patient might maintain really good central visual acuity for a prolonged period of time, for many years, until that atrophic lesion expands into the fovea. Only when that lesion expands into the center of the retina will we be able to detect a decline in visual acuity. That's different than patients who present with fovea. geographic atrophy lesions at baseline, where their vision is going to be negatively impacted at the baseline. And we would anticipate their vision to decline as that atrophy lesion progresses over time.

So, visual acuity really has not been a good endpoint. That's one of the reasons why we've not had good therapies for this disease. And we've really struggled with finding other endpoints that we can use in our clinical trials, that can be good biomarkers for studying whether our interventions are meaningful to help patients. Fortunately, we have discovered one, and it's an endpoint that's on an imaging test called a fundus autofluorescence image, which is basically like a photograph of the macula taken in a specific manner. We've been able to discern that the changes in the size of the atrophic lesion on fundus autofluorescence, over time, can be a good biomarker for progression of geographic atrophy. That is currently what has been used in recent clinical trials and is being used in ongoing clinical trials.

Besides fundus autofluorescence, we're still looking for other biomarkers that we can use to to find treatments. So currently, the mainstay of treatments is to recommend things such as good nutritional diet, we recommend patients maintain a healthy green leafy vegetable diet, eating like the Mediterraneans do. We also recommend that patients wear UV protected sunglasses while outdoors. We think exercising a few days a week, getting your heart rate going a few days a week, causes good metabolic changes in the retina to slow progression. And we recommend not smoking. So, doing things that are good for your cardiovascular health, we also think are good at lowering the progression rates of geographic atrophy.