Key Risk Factors Associated with GA

David Lally, MD, highlights risk factors associated with geographic atrophy.

Ryan Haumschild, PharmD, MS, MBA: Dr Lally, Dr Khanani did a great job of giving us the patient overview, and we understand it’s a disease of aging. But there are probably some other risk factors that we’ve heard about, like cardiovascular [disease]. Dr Lally, can you go a bit deeper into some of the risk factors that you’ve seen in patients developing geographic atrophy [GA] so our viewing audience has a better understanding, if they were to screen these patients or stratify, what are some of those key risk factors to pay even more attention to?

David Lally, MD: Arshad did a nice job touching on the risk factor part of this discussion. I think of AMD [age-related macular degeneration] as being a very multifactorial disease. I think genetics is a component, the environment is a component, the lifestyle of the patient is a component, and the general physiology of the patient would be a component. All of these things are separate buckets, and they can sum up and result in GA for different patients. As Arshad mentioned, far and away the No. 1 risk factor for developing GA is age. We know that if you’re over the age of 85, you have a 10-fold higher prevalence of developing late AMD than somebody who’s between the ages of 70 and 74. So the older you get, it almost exponentially, as Arshad mentioned, goes higher. Age is No. 1, that’s a nonmodifiable risk factor. But that’s something we look for in our clinic. If you’re an older patient, you want to be on the lookout for that, if they have a history of macular degeneration, are they developing GA?

When we look at the genetics of patients, we’ve learned a lot from our GWAS [genome-wide association studies] over the year that there are a lot of genetic risk factors that can be seen and linked to single nucleotide polymorphisms. We see a lot of them in the complement system, which I think we’ll get into. That was one of the first signals that we should be looking at maybe treatments of blocking complement, that a lot of these patients have these polymorphisms in their complement proteins, such as CFH [complement factor H], CFB, CFI, C2, C3, and some others that put patients at higher risks. So, if we have the availability to look at genetic testing, that can be helpful to give a risk score to these patients.

If we look at the physiology of the patient, certainly having a high body mass index can be a risk factor. Certain dyslipidemias can be risk factors, as well as other comorbidities, such as cardiovascular disease or diabetes. I look at the overall health of the patient. I find a lot of patients with COPD [chronic obstructive pulmonary disease], and this is not one I think we have great evidence for, but a lot of my patients with COPD are coming in with pretty advanced GA over time. Then some patients on certain systemic medications, so if we look at patients with thyroid disease, there are a lot of conflicting studies out there, but there’s some suggestion that patients who take certain thyroid medications or have hyperthyroidism, may be at risk for developing the advanced form of GA. So the systemic health of the patient matters.

If we look at the lifestyle of the patient, as Arshad mentioned, smoking is a big factor. We know that in almost a third of late AMD cases, there is some history of smoking with that patient. Then, what’s the diet intake of the patient? Is it a patient who is eating a lot of saturated, fatty acid, high cholesterol diet? That might be an increased risk for GA. Or a patient who has a low intake of antioxidants, healthy vitamins/minerals, or an unhealthy diet might be at a higher risk as well. Even things like high alcohol intake have been associated with late AMD. Then also, any patient who was employed in a profession that has high sunlight exposure, so they’re working over 8 hours a day, a construction worker who’s outside in the sunlight all day, may have a higher risk of developing [late AMD] further on in life.

There are other risk factors we look for that is also on imaging of the patient. I don’t know if I’m jumping the gun here, but our standard imaging modality in our office for macular degeneration is using the OCT, or optical coherence tomography, imaging device. We see certain features in the picture of patients with the intermediate stage of macular degeneration that are going to put them at higher risk to develop geographic atrophy later. Those features we look for would include the presence of hyper-reflective foci on the OCT image, if there’s a hyporeflective core of drusen, that’s a risk factor to go to atrophy, patients with subretinal drusenoid deposits would be a risk factor, and large pigment epithelial detachment.

The final one I should mention would be drusen volume, so patients with a lot of drusen are going to have a higher risk someday of going to geographic atrophy as opposed to those patients with just a few drusen. We do have a few imaging biomarkers that we can use and that referring doctors could be looking for with proper education, so if they see these features, maybe consider referring them to their local friendly retina specialist to look for the presence of GA.

Ryan Haumschild, PharmD, MS, MBA: That was a great overview, and speaking of local friendly retina specialists, we’ll turn to Dr Khanani for a second here. Can you go into a bit further detail about how patients are diagnosed? Dr Lally gave us a great overview of some of the things to look for and some of the referral patterns, and I really appreciate it. It was a great detail. Dr Khanani, is there anything you want to offer around the diagnosis, and even how you monitor these patients over time?

Arshad Khanani, MD: Absolutely. I think multimodal imaging obviously needs to be utilized on top of doing a dilated fundus exam. So a patient comes into me, we check visual acuity, front of the eye, we dilate, and we look in the back. On examination, you will see an area of atrophy, and if you don’t, you will see some changes as Dr Lally said on OCT, as well as on infrared and FAF [fundus autofluorescence]. Many of the referring doctors who send patients to us may not have FAF, or fundus autofluorescence, which basically tells you whether there is GA. But you can have sometimes incomplete atrophy, and you may not be able to see it on fundus autofluorescence, so that’s why OCT is an important tool to look for geographic atrophy or areas of high risk. That’s called iRORA [incomplete retinal pigment epithelium and outer retinal atrophy], which will be become what’s called cRORA [complete retinal pigment epithelium and outer retinal atrophy], or atrophy.

The bottom line is for the referring doctors, if they have a patient who they think has GA, whether they look for it on an examination, on color fundus photos, on fundus autofluorescence, on infrared imaging or OCT, then they should refer the patient. As you were saying, Ryan, the goal is we have to get these patients in early, and we have to treat them early so we don’t have retinal damage that’s too advanced. Somebody with 20/20 vision with a small GA lesion on the central [line of vision] may be a great candidate for treatment vs somebody who has a very large lesion centrally with legal blindness already.

None of the treatments in the pipeline are going to reverse the damage, none of them are going to stop it completely, but they are going to slow it. It’s an exponential benefit of treatment based on the data we have seen, and I’m sure we’re going to dive into those data, that the longer you treat, the more efficacy you see. That’s what we are looking for. So I think for general ophthalmologists or optometrists listening to this, any patient who you feel has GA, and even if it’s noncentral and away from the center with good vision, it’s time to send those patients in so we can do multimodal imaging and figure out if they are going to be good candidates for treatment.

Transcript edited for clarity.

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