Using Complement Inhibitors in GA Comes With Pros and Cons

A vote taken by the sound of applause rang out during an early morning session at the American Academy of Ophthalmology (AAO) 2026 annual meeting, where 2 experts discussed the pros and cons of using complement inhibitors to treat geographic atrophy (GA). Expert sentiment regarding complement inhibitors was assessed at the end of the debate, with many voting against their use in GA at this time.

Use of Complement Inhibitors Has Its Benefits

Diana V. Do, MD, vice chair of clinical affairs and professor of ophthalmology at the Byers Eye Institute at Stanford University, took up the pro side of the argument, and she started out with a simple question, asking how many in the room were either using complement inhibitors or were discussing them with their patients. “If I could just get 1 more person to consider it, then I would’ve won this debate,” she joked.

GA is not slowing down, said Do, which necessitates figuring out how to address the increased incidence that will come. The FDA has approved 2 complement inhibitors that can be used to treat GA, pegcetacoplan and avacincaptad pegol. “We’ve seen through randomized clinical trials that complement inhibitors…can slow the progression of GA by 21%. And this can be done through monthly treatment,” she said.

This slowing of progression can help patients preserve their vision longer, therefore keeping their independence and quality of life intact for longer as a result. Lesion growth was lessened, and the benefit improves the longer that the patient is using complement inhibitors. Do also sought to address the usual counterarguments, which include that visual acuity did not improve. She reiterated that this medication seeks to preserve what the patient has rather than resuscitate any vision.

She also noted that patients displayed a higher incidence of exudative age-related macular degeneration (AMD) and 1 in 4000 injections led to vasculitis. However, the incidence of vasculitis has diminished over time, which should address some safety concerns.

“By considering complement inhibitors for some patients, we can slow it, keep some of the retina, and preserve some of the vision function in our patients,” Do concluded. “It’s not perfect, but it is an option, so please consider it.”

Despite Promise, Complement Inhibitors Have Their Cons

Jennifer I. Lim, MD, a UIC distinguished professor of ophthalmology at the University of Illinois at Chicago, presented the counterargument for complement inhibitors, with an opening statement that she would not recommend their use at this time.

Lim noted that the Age-Related Eye Disease Study (AREDS) found that the Mediterranean diet and other types of treatment can safely achieve similar reductions in GA growth rate toward the foveal center. Along with this, she pushed back on Do’s presentation by noting that complement inhibitors do not restore vision and the risks outweigh the benefits for use in GA specifically.

AREDS1 Rx was shown to slow the rate of progression in GA by 36% whereas AREDS2 Rx slowed progression by 35%,² both exceeding that of complement inhibitors. The rate of GA progression was also slowed with the Mediterranean diet, with a HR of 0.71.³ On top of this, visual function and visual acuity showed no difference between treatment and control eyes when pegcetacoplan was tested. Lastly, Lim pointed out that complement inhibitors bring an increased risk of conversion to wet AMD, a risk of endophthalmitis, and a risk of severe visual acuity loss due to retinal vasculitis, all of which occurred more often in the treatment eyes than in control eyes.

“So it’s not surprising that the [Preferences and Trends] survey showed that the majority of GA patients are not treated with complement inhibitors,” said Lim. About 11% of US physicians do not use it, and only 11% of physicians in the US use it in more than 25% of their patients with GA. A total of 63% of US physicians were uncertain about the benefit of complement inhibitors or do not believe that complement inhibitors alter outcomes.

“I do not recommend complement inhibitors for GA at this time, because the AREDS and the [Mediterranean] diet can safely achieve similar reductions in GA growth rate toward foveal center,” Lim concluded.

Ultimately, most of the audience agreed with Lim in a vote taken by applause, but a considerable number of physicians voted on the pro side as well. Overall, eye doctors in the space should continue to use their best judgement and talk to their patients about options to approach their GA before starting treatment, as all methods demonstrate their own pros and cons.

References

1. Mukamal R. What to know about syfovre and izervay for geographic atrophy. American Academy of Ophthalmology. April 17, 2025. Accessed October 11, 2026. https://www.aao.org/eye-health/tips-prevention/syfovre-izervay-geographic-atrophy-amd-macular-deg
2. Keenan TDL, Agrón E, Keane PA, Domalpally A, Chew EY; Age-Related Eye Disease Study Research Group; Age-Related Eye Disease Study 2 Research Group. Oral antioxidant and lutein/zeaxanthin supplments slow geographic atrophy progression to the fovea in age-related macular degeneration. Ophthalmology. 2025;132(1):14-29. doi:10.1016/j.ophtha.2024.07.014
3. Keenan TD, Agrón E, Mares J, et al; Age-Related Eye Disease Studies (AREDS) 1 and 2 Research Groups. Adherence to the Mediterranean diet and progression to late age-related macular degeneration in the age-related eye disease studies 1 and 2. Ophthalmology. 2020;127(11):1515-1528. doi:10.1016/j.ophtha.2020.04.030