Introduction:　Choroidal　neovascularization　(CNV)　is　the　main　pathological　change　of　wet　age-related　macular　degeneration.　Anti-VEGF　drugs　are　the　most　commonly　used　treatment　for　CNV.　The　biggest　drawback　of　antiVEGF　drugs　is　the　recurrence　of　CNV,　which　requires　repeated　therapy　several　times.　Autophagy　activation　may　be　involved　in　reducing　the　therapeutic　effect　of　anti-VEGF　drugs.　So,　this　study　aims　to　elucidate　the　effect　and　mechanism　of　anti-VEGF　drugs　on　endothelial　autophagy　and　neovascularization　in　vitro.　Methods:　RF/6A　cells　were　randomly　divided　into　five　groups:　The　control　group,　hypoxia　group　(1%　O2,　5%　CO2,　94%　N2),　anti-VEGF　group　(group1:　Ranibizumab　100　mu　g/ml;　group2:　Aflibercept,　400　mu　g/ml;　group3:　Conbercept,　100　mu　g/ml).　Autophagy-related　proteins　were　examined　by　Western　blot.　RFP-GFP-LC3　was　used　to　detect　autophagy　and　autophagic　flow.　Subsequently,　we　used　autophagy　inhibitors　(3-MA　or　CQ)　to　inhibit　Conbercept　induced　autophagy　and　to　observe　its　effect　on　angiogenesis　in　vitro.　Proliferation,　migration,　and　tube　formation　of　endothelial　cells　can　be　used　to　study　neovascularization　in　vitro.　In　this　research,　the　CCK-8　assay　was　used　to　detect　cell　proliferation.　Cell　migration　and　tube　formation　were　assessed　by　wound　assay　and　matrix　method,　respectively.　Flow　cytometry　and　Tunel　were　used　to　detect　cell　apoptosis.　Finally,　the　mechanism　of　Conbercept　activated　autophagy　was　studied.　Western　blot　was　used　to　detect　the　expression　of　p53　and　DRAM　(damage-regulated　autophagy　modulator),　upstream　activators　of　autophagy.　Results:　The　protein　levels　of　Beclin-1　and　LC3-2/1　in　Ranibizumab　and　Conbercept　groups　were　significantly　higher　than　in　the　hypoxia　group(P　＜　0.05).　While　the　expression　of　P62　was　decreased　(P　＜　0.05).　The　autophagic　flux　was　showed　the　same　results.　However,　Aflibercept　showed　the　opposite　effect　on　autophagy.　Compared　with　the　Conbercept　group,　autophagy　inhibitor　3-MA　or　CQ　can　further　inhibit　cell　proliferation　and　promotes　cell　apoptosis　(P　＜　0.05).　Conbercept　significantly　inhibited　cell　migration　compared　with　the　hypoxia　group　(633.08　+/-　72.52　vs.　546.33　+/-　24.61),　while　the　autophagy　inhibitor　group　(3-MA　or　CQ)　had　a　more　obvious　inhibition　effect　(309.75　+/-　86.36　and　263.33　+/-　68.67)　(P　＜　0.05).　For　tube　formation,　the　number　of　tube　formation　was　decreased　significantly　in　the　Conbercept　group　(32.00　+/-　2.00)　compared　to　the　hypoxia　group　(39.00　+/-　1.53)　and　even　further　reduced　in　3-MA　or　CQ　group　(24.00　+/-　3.61,　20.00　+/-　2.65).　The　length　of　master　segments　in　the　hypoxia　group　was　15,668.00　+/-　894.11.　It　was　decreased　in　Conbercept　(13,885.34　+/-　730.03).　In　3-MA　or　CQ　group,　the　length　of　master　segments　dropped　further　(11,997.00　+/-　433.66,　10,617.67　+/-　543.21).　Compare　with　the　hypoxia　group,　the　expression　P53　and　DRAM　were　increased　in　the　Conbercept　group　(P　＜　0.05).　Autophagy-related　proteins　LC-3,　Beclin-1,　and　DRAM　were　inhibited　by　P53　inhibitor　Pifithrin-alpha　(PFT　alpha)　(P　＜　0.05).　Conclusion:　Ranibizumab　and　Conbercept　can　trigger　the　autophagy　of　vascular　endothelial　cells　while　Aflibercept　can　inhibit　it.　The　combination　of　Conbercept　and　autophagy　inhibitor　can　significantly　inhibit　the　formation　of　angiogenesis　in　vitro.　The　mechanism　of　autophagy　activation　is　related　to　the　activation　of　the　p53/DRAM　pathway.