The development of geographic atrophy (GA) has emerged as a potential long-term side effect of anti–vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (AMD). A 2014 report from the Comparison of Age-related Macular Degeneration Treatments Trial (CATT) showed that the incidence of GA was approximately 18 percent in patients who were treated for two years with intravitreal anti-VEGF agents. Eyes treated with ranibizumab had a higher risk than those treated with bevacizumab, and eyes treated monthly had a higher risk than those treated pro re nata (PRN).1
More recently, CATT investigators looked at the growth rate of GA and found that GA associated with ranibizumab grew slightly faster than that associated with bevacizumab.2
A surprising finding. “The new CATT results show that although there is a higher incidence of GA in the group receiving monthly injections, once GA develops there is no statistically significant difference in growth rate between monthly and PRN regimens,” said lead author Juan E. Grunwald, MD. Dr. Grunwald is professor of ophthalmology at the Hospital of the University of Pennsylvania and the Presbyterian Medical Center of Philadelphia, director of the Vivian S. Lasko Oculovascular Research Center at the Scheie Eye Institute, and principal investigator of the CATT Fundus Photography Reading Center.
This finding surprised investigators but is in line with recent research focused on genetic abnormalities that can affect the incidence of AMD pathologic features but do not necessarily affect the progression of these features,3 he noted.
Other risk factors. The study identified other potential risk factors associated with faster GA growth in anti-VEGF–treated patients. These include greater distance from the fovea, extrafoveal location of choroidal neovascularization (CNV), predominantly classic CNV, GA in the fellow eye, and epiretinal membrane.
For now, benefits trump risk. Dr. Grunwald said that researchers don’t know whether patients who receive anti-VEGF therapy have a higher risk of GA than those who receive no therapy because there is no natural history arm in CATT.
“Despite the risk of GA, patients’ vision got better over the two years that we looked at GA,” Dr. Grunwald pointed out. “The reason is that most of the GA developed away from the center of the fovea and didn’t interfere with central vision very much. It takes a few years for the GA that develops in a location away from the fovea to reach the fovea and truly disrupt vision and quality of life.”
Though patients need to be followed for a longer period to see if the GA becomes a problem, “What we can say now, at two years, is that the anti-VEGF agents are absolutely worthwhile,” said Dr. Grunwald.
1 Grunwald JE et al; CATT Research Group. Ophthalmology. 2014;121(1):150-161.
2 Grunwald JE et al; CATT Research Group. Ophthalmology. Published online Dec. 24, 2014.
3 Caire J. JAMA Ophthalmol. 2014;132(5):528-534.
Dr. Grunwald reports no related financial interests.
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