Large epidemiologic study reveals anti-VEGF effects on IOP changes. Photo: Leo Skorin, OD. Click image to enlarge.

Generally, few serious adverse events have been reported following intravitreal injections of anti-VEGF agents, but some large randomized clinical trials have suggested that these injections might lead to a sustained rise in intraocular pressure (IOP) to increase the risk of glaucoma. A large epidemiologic study compared the risk of IOP increase among the three intravitreal anti-VEGF agents in non-diabetic patients without pre-existing glaucoma, noting that the incidence of IOP increase was higher among bevacizumab and ranibizumab users compared with aflibercept users.

The researchers used a regional administrative database to identify anti-VEGF patients over a nine-year period and followed them to the first incidence of IOP increase. They excluded those with diabetes, pre-existing IOP increase or previous use of dexamethasone implants. The study identified 6,585 new users of anti-VEGF: 1,749 aflibercept, 1,112 bevacizumab and 3,724 ranibizumab. Women made up 60% of the cohort which had a mean age of 73.6 years.

The study conducted multivariable Cox regression analyses (intention-to-treat and as-treated) to evaluate the risk of IOP increase between aflibercept, bevacizumab and ranibizumab after adjusting for potential confounding variables. IOP increase was defined as the first record of steroid-induced glaucoma or neovascular glaucoma codes, or the use of two glaucoma drugs dispensed within 180 days of each other.

In the intention-to-treat analysis, the adjusted hazard ratio (HR) for incident IOP increase compared with aflibercept was higher for bevacizumab (HR=2.20) and ranibizumab users (HR=1.88) respectively. HRs remained even after excluding patients with a proxy of retinal vascular occlusion. The as-treated analysis confirmed such results (bevacizumab HR=3.76, ranibizumab HR=2.49).

The researchers suggested that repeated intravitreal injections of ranibizumab and bevacizumab may promote an inflammatory response due to increased placental growth factor levels in the eye. This could lead treated eyes to a higher risk of inflammatory-related increases in IOP than aflibercept.

“The results of our study are suggestive of an increased risk of IOP increase in non-diabetic patients who use bevacizumab and ranibizumab compared with users of aflibercept,” they concluded in their paper. “However, future studies are needed to confirm these results.”

Spini A, Giometto S, Donnini S, et al. Risk of intraocular pressure increase with intravitreal injections of vascular endothelial growth factor Inhibitors: a cohort study. Am J Ophthalmol. November 17, 2022. [Epub ahead of print].