Can frequent anti-VEGF injections increase glaucoma surgery risk?

Too much of a common age-related macular degeneration (AMD) treatment course in one year's time could inadvertently tip the scales toward another sight-threatening disease, a new study claims.

Published online in March's JAMA Ophthalmology, the study found that patients receiving seven or more intravitreous injections yearly of the anti-vascular endothelial growth factor (VEGF) drug, bevacizumab, were at a higher risk of eventually needing glaucoma surgery. Such results prove an especially concerning dilemma in patients with exudative (wet) AMD, who typically require more frequent anti-VEGF injections in a given year.  

To examine the correlation, researchers analyzed a dataset of more than 800 people in British Columbia who received bevacizumab injections for AMD between 2009 and 2013. Of those, only 74 were identified as eventually needing glaucoma surgery. Researchers found that patients receiving seven or more injections yearly were associated with a nearly 2.5-times greater risk of needing glaucoma surgery compared with those receiving only three or fewer.

Anti-VEGF injections have become the standard of care among patients with exudative AMD. A 2016 National Eye Institute-funded study showed that anti-VEGF injections preserved at least 20/40 vision—good enough to drive or read standard print—after five years of treatment, an outcome unthinkable only a decade earlier.

Bevacizumab, and other anti-VEGF drugs, work by stifling the growth of new or abnormal blood vessels in the eye that are the hallmark of exudative AMD. Leaking of these new blood vessels under the macula blurs central vision and can lead to rapid vision loss. However, advanced exudative AMD necessitates repeated monthly injections that can inadvertently elevate intraocular pressure (IOP) and potentially endanger the optic nerve.  

Injections' toll on IOP  

Although the study doesn't specifically examine the consequences of excessive anti-VEGF injections on IOP, the study infers glaucoma surgery is the end result of elevated IOP, says Murray Fingeret, O.D., founding member of the Optometric Glaucoma Society, who serves on the board of directors for The Glaucoma Foundation.  

"With the more injections that occur, the IOP goes up—that's been observed and there are a host of papers that have detailed this," Dr. Fingeret says. "But what makes this particular study unique is that it tracked how often glaucoma surgery is performed with the idea that the only reason glaucoma surgery would be performed is if intraocular pressure has gotten out of control, causing extensive damage."  

Researchers stress the findings aren't a causal relationship, but an association between the AMD treatment and glaucoma surgery. Additionally, it's still unclear why injections might elevate IOP. But what is clear is that anti-VEGF treatments are effective against AMD-related vision loss, and therefore, shouldn't be thrown out with the bath water, so to speak.  

"Because of the devastating nature of wet AMD, the downside is so significant that you really don't have a choice," Dr. Fingeret says. "This is really the best therapy for a blinding condition."  

Given that optometry is intimately involved in the comanagement and monitoring of AMD patients, this study underscores the need for doctors to continue checking IOP and examining the optic nerve throughout an anti-VEGF treatment course.  

Access AOA's clinical practice guidelines, Care of the Patient with Age-Related Macular Degeneration, and Care of the Patient with Open-Angle Glaucoma.