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Robert L Avery, Gabriel M Gordon; Does Anti-VEGF Treatment for AMD Lower the Risk of Neovascularization in the Fellow Eye? A Meta-analysis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1474.
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Anti-VEGF agents escape into the systemic circulation after intravitreal injection (IVI), and reduce circulating VEGF. These drugs have been detected in fellow eyes, and numerous case reports as well as several retrospective studies have demonstrated retinal effects in fellow eyes after IVI. The systemic exposure (area under the concentration curve) of ranibizumab after IVI is >10 fold less than bevacizumab or aflibercept, and it is conceivable that it would be less likely to demonstrate an effect on development of neovascular age-related macular degeneration (nAMD) in fellow eyes than bevacizumab or aflibercept. Evaluation of individual clinical trials has not demonstrated a significant difference in fellow eye nAMD development, only trends. To evaluate larger numbers of patients, a meta-analysis was performed.
Meta-analysis of prospective, randomized studies of anti-VEGF treatment of nAMD in which the development of fellow eye nAMD was evaluated. As pharmacokinetic studies have demonstrated ranibizumab to have much less systemic exposure following IVI than bevacizumab or aflibercept, it was considered the lower systemic exposure agent when compared to these agents, and the higher systemic exposure agent when compared to sham arms.
Literature search revealed 3 studies of 5 trials (ANCHOR, MARINA, CATT, VIEW 1, VIEW 2) in which development of fellow eye nAMD was assessed. When comparing the arms with more systemic exposure to anti-VEGF agents to arms with less or no systemic exposure, a decreased risk of fellow eye nAMD was found with greater systemic anti-VEGF exposure, odds ratio 0.80 (0.66-0.97), p=0.02. (Table 1)
This study provides evidence of the biologic plausibility that following IVI, anti-VEGF agents escape the eye at concentrations sufficient to potentially have effects on distant organs, such as fellow eyes.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Forest plot of the development of nAMD in fellow eyes.
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