Three anti-VEGF drugs are in clinical use for treatment of wet age-related macular degeneration (wAMD). These are Lucentis (ranibizumab), off-label Avastin (bevacizumab), and Eylea (ranibizumab).
- The rate of stroke from intravitreal injections of Lucentis was found in the early clinical trials to be 0.2% (1 of 525) in the combined group of patients compared to 0.4% (1 of 260) in the control arms. No followup studies, however, were done to confirm the risk. (1)
- In 2015, The Centre for Adverse Reactions Monitoring (CARM) received two reports of stroke after intravitreal injection of Avastin. Again, the association was not confirmed by further research. (2)
- In addition, some evidence has been reported (3,4) showing a possible association between Eylea and incidence of stroke, with followup research still to come.
This evidence has caused concern among patients who must undergo anti-VEGF injections to save their eyesight. Even though the evidence has been empirical only, doctors have been rightfully warned to initiate the treatment only if the benefits outweighed the risk of harm. And then, patients have been instructed to seek immediate medical attention if they developed any symptoms of stroke.
Good News
A 5-year cohort study of 504 patients from Olmsted County, Minnesota has found no consistent associations in the risk of stroke, myocardial infarction, or death among wAMD patients receiving anti-VEGF injections compared with control groups with and without wAMD.(5)
This appears to be the first effort to scientifically pursue the evidence, and the findings may help to ease the concern of both patients and doctors. More such studies, however, should be initiated before any change in protocol is made.
REFERENCES
1 https://www.lucentis.com/hcp.html
2 Risk of Stroke with Ranibizumab (Lucentis), Bevacizumab (Avastin) and Aflibercept (Eylea), Administered by Intravitreal Injection (Prescriber Update 36(1): 9. 5. March 2015)
3 Bressler NM, Boyer DS, Williams DF et al. 2012 Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials (Retina. 32: 1821-1828.)
4 Pratt NL, Ramsay EN, Kemp A, et al. Ranibizumab and risk of hospitalisatino for ischaemic stroke and myocardial infarction in patients with age-related macular degeneration: a self-controlled case-series analysis (Drug Safety. 37: 1021-1027. 2014)
5 Association of Intravitreal Anti–Vascular Endothelial Growth Factor Therapy With Risk of Stroke, Myocardial Infarction, and Death in Patients With Exudative Age-Related Macular Degeneration. Lauren A. Dalvin, MD , et al (JAMA Ophthalmol. Published online January 31, 2019. doi:10.1001/jamaophthalmol.2018.6891)