Visual acuity outcomes of anti-VEGF treatment for neovascular age-related macular degeneration in clinical trials

Anti-VEGF treatment for neovascular age-related macular degeneration (nAMD) has been evaluated in clinical trials. To select the best anti-VEGF drug and the best treatment regimen for nAMD, a thorough understanding of the characteristics of each anti-VEGF drug and treatment regimen is essential. In this review, we summarized visual acuity (VA) changes in 30 previous clinical trials of anti-VEGF treatment for nAMD. In most studies, ranibizumab, aflibercept, and brolucizumab improved the VA by 6 to 12 letters from the baseline VA of 50-65 letters and maintained the VA improvement regardless of the treatment regimen; the VA improved from 0.2-0.4 to 0.3-0.7 in Snellen equivalents. The improvement was rapid during the first month and became slower after the second injection, and 60% to 90% of the VA improvement was attained within the first 3 months. The upper limit of the VA improvement should be determined according to eyes with nAMD themselves, not according to anti-VEGF drugs or treatment regimens. Since a fixed regimen can result in overtreatment, whilst a pro re nata regimen can result in insufficient treatment, a treat-and-extend regimen would be optimal to treat nAMD. Insufficient treatment fails to improve VA to the upper limit and/or to maintain the improved VA, whereas overtreatment can cause macular atrophy. One study reported no difference in the risk of macular atrophy between ranibizumab and aflibercept, whilst many studies have suggested that aflibercept causes more choroidal thinning, one of the risk factors for macular atrophy, than does ranibizumab. Further evaluation of drugs and regimens should be performed from the viewpoint of complications and minimum number of injections required to improve and maintain VA.