‘Unclear’ if Serial Anti-VEGF Injections Result in Sustained IOP Increases

No clear difference in patients’ intraocular pressures (IOP) occur following treatment with anti-vascular endothelial growth factor (VEGF) agents at either 12- or 24-months compared with controls, according to a study in Ophthalmology. But, researchers explain, “imprecision precludes definitive conclusions with the available data.”

The investigators conducted a network meta-analysis of 26 randomized control trials of 12,522 eyes comparing anti-VEGF agents with each other or with a control for the treatment of neovascular age-related macular degeneration (nAMD), retinal vein occlusions (RVO), or diabetic macular edema (DME). Anti-VEGFs analyzed included aflibercept (2.0mg), bevacizumab (1.25mg), ranibizumab (0.3mg and 0.5mg), along with noninjection controls. They also performed pairwise meta-analysis and Bayesian network meta-analysis examining the proportion of patients at 12- and 24-months whose IOP: 

• Increased ≥5 mm Hg from baseline on consecutive visits 
• Increased ≥10 mm Hg from baseline at any visit 
• Was ≥21 mm Hg on consecutive visits
• Was ≥25 mm Hg at any visit 
• Was ≥30 mm Hg at any visit 
• Prompted initiation of IOP lowering medications and 
• Increased as per the clinicians’ discretion. The certainty of evidence was determined using Cochrane Collaboration’s Risk of Bias Tool and GRADE (Grading of Recommendations Assessments, Development and Evaluations) guidelines

Researchers found 83 of 84 network estimates for comparisons between anti-VEGF agents demonstrated no statistically significant difference between groups. Ranibizumab 0.5mg had higher rates than bevacizumab of IOP measurements ≥30 mm Hg at 12-months. In addition, 53 of 56 network estimates for comparisons between anti-VEGF agents and controls found no statistically significant difference between groups. 

“Ranibizumab 0.5mg had higher rates of consecutive IOP increases ≥5 mm Hg at 24-months (low certainty of evidence) and higher rates of IOP increases as per the clinicians’ discretion at 12 and 24 months (low and very low certainty of evidence respectively),” investigators report. “The 95% credible intervals in all comparisons without statistically significant effects did not rule out important clinical effects.”

The study’s limitations include, because IOP was not the primary outcome of included trials, no standardized method of measuring IOP or standardized time at which IOP was measured across included trials existed. Also, follow-up frequency varied across and sometimes in trials, possibly making IOP rate increases more biased by more frequent measurement. IOP increase definitions differed too, which might have limited the power of outcome assessments. 

“While the current study found no conclusive evidence of IOP increases in patients receiving anti-VEGF therapy, the analysis was limited by imprecision and may not be sensitive enough to identify small proportions of patients who do experience clinically meaningful increases in IOP,” according to the study. 

More follow-up study is needed. Researchers of this meta-analysis have ideas about how to conduct those studies, too. “We propose that future studies utilize the recommended thresholds for defining ocular hypertension as defined by the National Institute for Health and Care Excellence (NICE) of 24 mm Hg. We also propose further standardization in IOP measurement protocols to help unify future studies, and suggest that future studies include measurements related to glaucomatous disease to facilitate evidence synthesis to inform clinical decision-making.”

Reference

Nanji K, Sarohia GS, Kennedy K, Ceyhan T, McKechknie T, et al. The 12- and 24-month effects of intravitreal ranibizumab, aflibercept and bevacizumab on intraocular pressure: a network meta-analysis. Ophthalmol. Published online December 3, 2021. doi:10.1016/j.ophtha.2021.11.024