Ryan Haumschild, PharmD, MS, MBA: One thing that’s really important to payers and employers is making sure we improve the quality of life of the patients we’re treating. We talked about this being an aging disease, and one of the things we want to be thoughtful of is there are a lot of other comorbidities by that time that patients need to take care of, let alone having independent living. You have fall risk and things like that, and so quality of life becomes really important as we monitor it. It’s also a leading indicator for a lot of payers as they’re evaluating treatments; it’s clinical efficacy and safety, but quality of life is something we’re looking at. Dr Lally, I want to turn this to you because I know you’re treating a lot of patients and you have a lot of experience. How does vision loss associated with geographic atrophy [GA] impact patient quality of life, and how can this vision loss even impact a patient’s mental health?

David Lally, MD: It’s a really important question, and I think to start it’s a hard question to answer with science with our clinical trials. The first important take-home message is that it is a heterogeneous disease in terms of its presentation. Some patients will develop the first sign of atrophy right in the center of the retina in the fovea, the part of the retina that we use for visual acuity when we’re reading an eye chart. If that patient develops center-involving foveal GA, they’re going to start noting sudden decreased central vision immediately as that’s happening. This disease is progressive and it’s chronic and it’s unrelenting, and we know that it gets worse. I typically follow these patients in my office every 6 months. And I can tell you that every 6 months when that patient is coming in to see me, they’re complaining they’re getting worse, and they’re very concerned.

It’s a very different presentation than our patients with neovascular age-related macular degeneration [nAMD], where those patients have a real sudden, acute loss of vision. Often we can restore a lot of the vision with our treatments and maintain the patient’s vision to where they’re coming in after their treatment saying, “my vision has been the same.” That’s very different from our patients with GA, especially the foveal-involving patients, where every 6 months I find they’re saying it’s getting worse. So what are they noting? The most common thing they note far and away is that things up close are tougher, specifically with reading. They make complaints like, “It’s harder to read, it’s harder to see the checkbook, certain letters are missing when I’m reading,” and it’s unrelenting. It’s every couple of months they’re noticing it getting worse and worse, and that’s very concerning for these patients.

You talk about their mental health. There are no good studies I’ve seen that have looked at mental health changes related to GA. I’ve seen it related to nAMD, and certainly, we can see that as you progress along the spectrum of nAMD and get worsening disease and vision, we see associations with worsening mental health. That study needs to be done in GA as well, but I can tell you anecdotally with my patients that they are very concerned. Anxiety would be No. 1 on their list, and depression would be No. 2. If we look at what type of health issue they fear the most, losing vision in my understanding is the No. 2 thing patients are most concerned about with their health in the world, No. 1 being developing cancer. We all cherish our vision, and when you’re a patient with GA and you’re noticing this unrelenting progressive deterioration over the years, it causes a lot of mental health issues. Reading would be No. 1, I think 100% of patients would complain of that. No. 2 would be driving. If patients are still legal to drive, they start to complain that it gets harder to see the street signs. It gets harder to find the exit to get off of the highway. They can’t drive at night any longer, and those things continue to progress over time.

If we have a patient who has nonfoveal GA, so they present where their atrophic lesion develops first off of center, they might have more nonspecific complaints; again a little more trouble driving, a bit tougher reading, where maybe a letter off to the side of the word is missing. As those atrophic lesions grow over time and they start to encroach on the foveola or the center of the retina, that’s when they really start to notice an uptick in the speed of vision loss. They might be noting more nondescript symptoms for a few years, but I find as soon as those atrophy lesions expand and get very close to the foveola, they start complaining dramatically as they notice that atrophy get into the center.

If you’re a payer listening on the call, it’s very hard for us to measure this because of the heterogeneity of these patients. Some patients have atrophic lesions in the center, some off to the side, some have 1 spot of atrophy, and some have multifocal spots of atrophy. When it’s a heterogeneous bucket, it’s hard to pull and tease out really good clinical trial results for looking at these patient-reported outcomes. But rest assured that doctors seeing these patients in the clinics are noting unrelenting vision loss, and they have severe mental health issues because of this.

Ryan Haumschild, PharmD, MS, MBA: Wow, that was a great overview, and I appreciate you bringing in your real-world experience when treating patients. I know this is something you’re very close to. That may not be teased out or studied as clearly, but I think your anecdotal stories and experience go a long way. Dr Khanani, because you also are practicing and you’re seeing patients, I wanted to give you an opportunity to respond to this question as well. Do you see an impact on your patients’ quality of life, and do you also see it potentially impacting the mental health of the patients?

Arshad Khanani, MD: Definitely, Ryan. I think what Dr Lally said was pretty comprehensive, but I’ll add a few things here. No.1 is these patients are scared to lose their independence, and they know that their grandmother, or mother, or parents, or sibling went blind from this disease. There’s this fear about, “How much longer do I have before I won’t be able to drive and I will need help to write my checks?” It’s a very difficult situation for these patients because we kept telling them, up until now, “There’s no treatment, and we know you’re going to go blind, and we hope your disease doesn’t grow that fast.” In my opinion, there are 2 tranches of vision loss that happen with GA. One is as Dr Lally was saying, when nonfoveal hits the fovea, then you go from 20/20, 20/30, 20/40, to one day they’ll come in and say, “I can’t see anymore,” and it will be 20/80, 20/100, and even legal blindness. They adapt to that, and then over time they lose more cells, and now they have small areas of functioning photoreceptors. And then they drop, and now they are completely miserable because they can’t function.

I think our job is to intervene early, to make sure we have treatment available for all patients at different stages of disease because we are going to make an impact in terms of slowing it. Once you are legally blind with poor vision, many of these patients have what’s called Charles Bonnet syndrome, where they start hallucinating. They know these are not real, but they start to see flowers, they start to see things, and that also affects them mentally. To Dr Lally’s point, I think many of these patients end up with depression.

From a payer perspective, if you have a patient who loses their independence, they’re at a higher risk for car accidents because many of them may drive even though we recommend not to because they have no help. Many of the patients fall, break their hips, injure themselves, because they can’t see. There are accidents, they cut their fingers while cooking, or cannot see the fire, etc. There are all these aspects that are part of having poor vision. I think that’s why it’s important to preserve vision, so the quality of life of the patient is much better. And actually the health care cost will be much less because they will not end up in the emergency department with a major fracture because they fell when they didn’t see the piece of furniture that was in their way.

Ryan Haumschild, PharmD, MS, MBA: Great comments, thank you so much for going through that.

Transcript edited for clarity.