Anti-VEGF Injection Frequency Linked With Elevated Risk of Geographic Atrophy

Investigators say the relationship is not necessarily casual and that eyes that receive more injections may have more aggressive disease.

In eyes with neovascular age-related macular degeneration (nAMD), a higher frequency and number of anti-vascular endothelial growth factor (VEGF) injections are associated with the development of geographic atrophy (GA), according to a study published in Retina. 

GA is considered a complication of advanced nAMD that can result in permanent loss of vision, according to the study. Recent research suggests a potential relationship between anti-VEGF treatment administration and the development or progression of GA.  

Researchers in Canada estimated the incidence and progression of GA after intravitreal injections of anti-VEGF agents in patients with nAMD. They searched Ovid MEDLINE, EMBASE, and Cochrane CENTRAL from inception to May 2020. The investigators included studies on the development or progression of GA in eyes with nAMD after anti-VEGF treatment. 

They reviewed 31 articles, including 4609 eyes of 4501 patients (mean age 78.2±2.4 years,  59.6±7.8% women). The researchers found that eyes received a mean of 17.7 injections in 35.2 months. The frequency of GA at baseline was 9.7%. At the conclusion of follow-up, the mean incidence of GA was 30.5%. 

At the final follow-up, there was a positive, moderate linear association between the mean total number of injections and GA incidence (R2 =0.30; P =.01). The analysis showed that monthly treatment was associated with a significantly increased risk for developing GA relative to pro re nata (relative risk=1.40, 95% CI=[1.21–1.61], P <.001). 

“Risk factors for GA development included GA in the fellow eye, retinal angiomatous proliferation, drusen, and reticular pseudodrusen,” the researchers noted. “None of the reviewed articles directly analyzed the causality of this relationship, which could be influenced by the natural progression of nAMD itself. Indeed, eyes that received injections more frequently may have had more aggressive underlying nAMD, which itself is a risk factor for greater natural progression of GA.”

The study noted several limitations. For example, baseline factors that may influence GA outcomes such as smoking, duration of disease and ethnicity, were not taken into account. Additionally, the meta-analysis is limited by the variability of techniques across the various studies. Further, many studies had a short duration of follow-up.

“At present, intravitreal injections of anti-VEGF agents are the most effective treatment to preserve vision in eyes with nAMD,” according to the report. “However, strategies should be used for those at high risk of GA to limit the number of injections whenever possible while preserving visual acuity gains and maintaining close follow-up.”


Eshtiaghi A, Issa M, Popovic MM, Muni RH, Kertes PJ. Geographic atrophy incidence and progression after intravitreal injections of anti-vascular endothelial growth factor agents for age-related macular degeneration. Retina. 2021;41(12):2424-2435. doi:10.1097/IAE.0000000000003207