Geographic atrophy (GA), the advanced atrophic form of age-related macular degeneration (AMD), is being diagnosed more often: among US Medicare beneficiaries 65 and older, GA prevalence more than doubled from 0.34% in 2014 to 0.73% in 2021.1
Untreated GA lesions grow a mean of 1.6 mm2 per year, and in a long-term natural history cohort, 30% of fovea-sparing eyes progressed to foveal involvement over a median of 24 months.2 With complement inhibitors now supported by more than 3 years of data, the clinical question is shifting from whether GA progression can be slowed to which patients should commit to years of injections to slow it.
Join Priya Vakharia, MD, and Jonathan Brugger, MD, MBA, as they discuss how long-term data from the GATHER2 and GALE studies are helping clinicians approach treatment decisions for patients with geographic atrophy.
Dr. Vakharia is a vitreoretinal surgeon at Retina Vitreous Associates of Florida. She regularly speaks at industry conferences and events and serves as a reviewer for multiple medical journals. Dr. Brugger, a practicing surgeon at Carolina Eyecare, is actively involved in research and has functioned as an investigator on new treatments for diabetic retinopathy and macular degeneration.
Complement inhibitor therapy for GA fast facts
- Data from the GATHER2 and GALE studies suggests the benefits of complement inhibition treatments may increase the longer they’re used.
- Functional data, such as microperimetry findings from GALE, are helping clinicians better understand how these treatments could help preserve retinal function.
- Clinicians should weigh the potential benefits of intravitreal injections against the treatment burden for their patients.
- Long-term safety data is helping clinicians better understand potential complications, such as neovascular AMD and intraocular inflammation.
- When developing treatment plans, clinicians should consider factors such as patient preference, disease progression, and existing vision.
Deeper dive: Redefining GA treatment decisions
GA is a retinal disease that can be challenging to manage because of the permanent damage it causes and the large treatment burden.
Dr. Vakharia and Dr. Brugger discussed how long-term data from the GALE and GATHER2 studies has given clinicians a better understanding of emerging treatments, and how they can use this new information to support patients and their families.
How long-term data is changing treatment expectations
Dr. Vakharia and Dr. Brugger explained that long-term data from the GALE and GATHER2 studies suggests the benefits of treatment with complement inhibitors may increase over time.
Specifically, they noted that:
- The GATHER2 study found a 40.5% reduction in GA lesion growth versus projected sham at 42 months with continuous avacincaptad pegol treatment.3
- The GALE study found that patients who received a monthly injection of pegcetacoplan experienced a 45% reduction in GA growth at 30 months, with the treatment's effects improving over time.4
- GALE functional data showed an 18% reduction in the development of new scotomatous points at 36 months with monthly injections compared to projected sham.5
Taken together, these findings suggest the potential benefits of complement inhibition may increase over time. However, both doctors acknowledged that this means changing the way these treatment options are presented to patients. It’s important they understand there’s no quick fix, so clinicians need to set expectations.
“I think that the most important thing is that these treatments are a commitment, and that the effects increase over time.”
Some GA patients may benefit from earlier treatment
Since long-term data suggest the benefits of complement inhibition could potentially increase over time, Dr. Brugger and Dr. Vakharia said that clinicians should start thinking about when to begin GA treatment.
For instance, functional data from the GALE study found that treatment was associated with a reduction in the development of new scotomatous points as GA progresses. This is especially important, since slowing vision loss could mean a patient can maintain their independence longer or witness important life events.
Dr. Brugger noted, “18 months can really be a lifetime if aligned with [a patient’s] immediate life goals, [such as] births in the family, graduations, weddings, [and] anniversaries.” Still, a GA diagnosis doesn’t necessarily mean treatment needs to begin right away.
Dr. Vakharia shared that she often makes recommendations based on a patient's symptoms and disease progression. Someone who’s already experiencing blurry vision, blind spots, or vision loss in their fellow eye may need to start receiving injections sooner than someone who isn’t.
Safety and treatment burden are important considerations
Next, Dr. Brugger and Dr. Vakharia explained how long-term data has helped clinicians better understand safety concerns around complement inhibitors. Early results suggested that patients using these medications might be more likely to experience complications such as neovascular AMD, inflammation, and retinal vasculitis.
While it’s true these complications are possible, both doctors noted they’re now less concerned about the risk. That’s because if something like wet AMD is detected, clinicians can monitor it via OCT and manage it with effective treatments. Dr. Brugger even shared that he tends to prescribe avacincaptad pegol over pegcetacoplan because studies show it may present a lower risk of inflammation and retinal vasculitis.6
At the same time, both Dr. Brugger and Dr. Vakharia said treatment burden should always be considered when counseling patients with GA. Complement inhibitors require monthly or every-other-month (EOM) injections for years, which can be a big ask for certain individuals, especially those who are older or living with other health conditions.
“I understand that committing a patient to years of monthly or every other month intravitreal injections can be burdensome. But also, now that we have durability data that extends past that 3-year mark…I think that really changes things.”
Dr. Vakharia shared that she typically uses EOM dosing to make long-term treatment more manageable, while Dr. Brugger moved to a monthly approach after reviewing long-term efficacy data. Both doctors emphasized that there isn’t a single, “right” way to manage GA. Instead, they encouraged clinicians to weigh the safety, efficacy, and treatment burden for each of their patients.
Take patient preference into account when developing a treatment plan
Even with all of the new data on complement inhibitors, Dr. Brugger and Dr. Vakharia stressed the importance of patient education and preference when making treatment recommendations.
Specifically, they mentioned how important it is that patients understand these treatments can’t restore vision, and instead, will only help slow disease progression. Both acknowledged that some patients may not understand this concept or may have unrealistic expectations about outcomes.
In these situations, clinicians may benefit from asking family members about the patient’s treatment goals. Family members can also help reinforce the information discussed during visits and make sure their loved one understands what treatment involves.
When thinking about which patients will most benefit from complement inhibitors, Drs. Brugger and Vakharia suggested considering several factors, including the individual’s:
- Symptoms
- Fellow-eye status
- Remaining vision
- Medical co-morbidities
- Willingness and ability to participate in ongoing treatment
Keeping these factors in mind can help you determine if a patient is a good candidate.
“When I see GA, I'm definitely going to talk to the patient about it. If I see GA that's progressing, I'm going to talk to them about treatment. [At the same time,] I think everyone deserves to make their own decision. It's not my decision to make.”
This article was written by Chad Birt based on the recorded conversation between Drs. Vakharia and Brugger.
