Aflibercept (Eylea™, Regeneron Pharmaceuticals, Inc., and Bayer Pharma AG, Berlin, Germany) is a decoy receptor fusion protein, composed of the second domain of human VEGF receptor 1 and the third domain of VEGF receptor 2, which are fused to the Fc domain of human IgG1. Aflibercept can downregulate both VEGF-A and placental growth factor, which are synergistic for pathologic angiogenesis. The MYRROR study, a randomize d controlled trial, demonstrated the efficacy of intravitreal aflibercept 2 mg over the sham injection for 121 patients with subfoveal or juxtafoveal mCNV⁽¹⁰⁾. The authors used one injection at baseline then PRN treatment according to (I) reduction in visual acuity more than 5 letters from the previous visual examination; (II) central retinal thickness increases more than 50 μm from the previous optical coherence tomographic examination; (III) new or persistent cystic retinal changes, subretinal fluid, or pigment epithelial detachment; (IV) new or persistent mCNV or bleeding. The 6-month results showed that the aflibercept group gained mean 12.1 letters, significantly better than the sham group having mean 2.0-letter loss. Decrease of central retinal thickness and mCNV size was more prominent in the aflibercept group than in the sham group. The sham group was allowed to receive PRN ranibizumab injections from month 6 to month 12. The 1-year results showed that despite visual improvement in 3.9 letters in the prior sham group after administration of aflibercept, still significantly worse than prior aflibercept group with 13.5-letter visual gain. The median number of prior aflibercept group was nearly two injections over 12 months, mostly before month 2. No significant ocular or nonocular safety events were observed except macular hole after afl ibercept administration in one patient. The authors conclude aflibercept is superior to sham for managing mCNV. Delayed afl ibercept treatment can lead to irreversible visual impairment.

Conclusions

In summary, there are two approved pharmacotherapy for treating mCNV, ranibizumab and aflibercept, categorized as anti-VEGF agents. They all show superior ability to improve vision and reduce macular thickness, comparing with sham injections or vPDT. There is no severe ocular or systemic adverse reaction reported in studies associated with anti-VEGF for mCNV. Intravitreal anti-VEGF requires baseline one injection then PRN retreatment according to either visual acuity or anatomical changes. Prompt treatment with these agents can lead to a better outcome.