Emergence of dual VEGF and PDGF antagonists in the treatment of exudative age-related macular degeneration

References

• Congdon N, O’Colmain B, Klaver CC et al. Causes and prevalence of visual impairment among adults in the United States. Arch. Ophthalmol. 122(4), 477–485 (2004).
   PubMed Web of Science ®Google Scholar
• Rein DB, Wittenborn JS, Zhang X, Honeycutt AA, Lesesne SB, Saaddine J. Forecasting age-related macular degeneration through the year 2050: the potential impact of new treatments. Arch. Ophthalmol. 127(4), 533–540 (2009).
   PubMedGoogle Scholar
• Bressler NM, Bressler SB, Fine SL. Age-related macular degeneration. Surv. Ophthalmol. 32(6), 375–413 (1988).
   PubMed Web of Science ®Google Scholar
• Ferris FL 3rd, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch. Ophthalmol. 102(11), 1640–1642 (1984).
   PubMed Web of Science ®Google Scholar
• Young RW. Pathophysiology of age-related macular degeneration. Surv. Ophthalmol. 31(5), 291–306 (1987).
   PubMed Web of Science ®Google Scholar
• The Age-Related Eye Disease Study (AREDS): design implications. AREDS report no. 1. Control Clin. Trials 20(6), 573–600 (1999).
   Google Scholar
• Ferris FL, 3rd, Wilkinson CP, Bird A et al. Clinical classification of age-related macular degeneration. Ophthalmology 120(4), 844–851 (2013).
   PubMed Web of Science ®Google Scholar
• Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY. Age-related macular degeneration. Lancet 379(9827), 1728–1738 (2012).
   PubMed Web of Science ®Google Scholar
• Maiman TH. Stimulated optical radiation in ruby. Nature 187(4736), 493–494 (1960).
   Web of Science ®Google Scholar
• Krauss JM, Puliafito CA. Lasers in ophthalmology. Lasers Surg. Med. 17(2), 102–159 (1995).
   PubMed Web of Science ®Google Scholar
• Bridges WB. Laser oscillation in singly ionized argon in visible spectrum (method - pulsed d-c discharge transitions - 4p to 4s, 4p to 3d e). Appl. Phys. Lett. 4(7), 128 (1964).
   Web of Science ®Google Scholar
• Argon laser photocoagulation for senile macular degeneration. Results of a randomized clinical trial. Arch. Ophthalmol. 100(6), 912–918 (1982).
   PubMedGoogle Scholar
• Yannuzzi LA. A new standard of care for laser photocoagulation of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Data revisited. Arch. Ophthalmol. 112(4), 462–464 (1994).
   PubMedGoogle Scholar
• Schmidt-Erfurth U, Miller JW, Sickenberg M. et al. Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study. Arch. Ophthalmol. 117(9), 1177–1187 (1999).
   PubMedGoogle Scholar
• Miller JW, Schmidt-Erfurth U, Sickenberg M. et al. Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of a single treatment in a phase 1 and 2 study. Arch. Ophthalmol.117(9), 1161–1173 (1999).
   PubMedGoogle Scholar
• Schmidt-Erfurth U, Miller J, Sickenberg M et al. Photodynamic therapy of subfoveal choroidal neovascularization: clinical and angiographic examples. Graefes Arch. Clin. Exp. Ophthalmol. 236(5), 365–374 (1998).
   PubMed Web of Science ®Google Scholar
• Bressler NM. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-tap report 2. Arch. Ophthalmol. 119(2), 198–207 (2001).
   PubMed Web of Science ®Google Scholar
• Barr H, Tralau CJ, Macrobert AJ et al. Photodynamic therapy in the normal rat colon with phthalocyanine sensitisation. Br. J. Cancer 56(2), 111–118 (1987).
   PubMed Web of Science ®Google Scholar
• Chen J, Keltner L, Christophersen J et al. New technology for deep light distribution in tissue for phototherapy. Cancer J. 8(2), 154–163 (2002).
   PubMed Web of Science ®Google Scholar
• Moore JV, West CM, Whitehurst C. The biology of photodynamic therapy. Phys. Med. Biol. 42(5), 913–935 (1997).
   PubMed Web of Science ®Google Scholar
• Ferrara N. Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy. Nat. Med. 16(10), 1107–1111 (2010).
   PubMed Web of Science ®Google Scholar
• Terman BI, Dougher-Vermazen M, Carrion ME et al. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem. Biophys. Res. Commun. 187(3), 1579–1586 (1992).
   PubMed Web of Science ®Google Scholar
• Kim KJ, Li B, Winer J et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362(6423), 841–844 (1993).
   PubMed Web of Science ®Google Scholar
• Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935), 1306–1309 (1989).
   PubMed Web of Science ®Google Scholar
• Aiello LP, Avery RL, Arrigg PG et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N. Engl. J. Med. 331(22), 1480–1487 (1994).
   PubMed Web of Science ®Google Scholar
• Adamis AP, Miller JW, Bernal MT et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am. J. Ophthalmol. 118(4), 445–450 (1994).
   PubMed Web of Science ®Google Scholar
• Lopez PF, Sippy BD, Lambert HM, Thach AB, Hinton DR. Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes. Invest. Ophthalmol. Vis. Sci. 37(5), 855–868 (1996).
   PubMed Web of Science ®Google Scholar
• Kvanta A, Algvere PV, Berglin L, Seregard S. Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor. Invest. Ophthalmol. Vis. Sci. 37(9), 1929–1934 (1996).
   PubMed Web of Science ®Google Scholar
• Aiello LP, Pierce EA, Foley ED et al. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc. Natl Acad. Sci. USA 92(23), 10457–10461 (1995).
   PubMed Web of Science ®Google Scholar
• Adamis AP, Shima DT, Tolentino MJ et al. Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. Arch. Ophthalmol. 114(1), 66–71 (1996).
   PubMed Web of Science ®Google Scholar
• Campochiaro PA, Hackett SF. Ocular neovascularization: a valuable model system. Oncogene 22(42), 6537–6548 (2003).
   PubMed Web of Science ®Google Scholar
• Nussenblatt RB, Ferris F. 3rd. Age-related macular degeneration and the immune response: implications for therapy. Am. J. Ophthalmol. 144(4), 618–626 (2007).
   PubMed Web of Science ®Google Scholar
• FDA approves new drug treatment for age-related macular degeneration. FDA News Release, 20th December (2004).
   Google Scholar
• Gragoudas ES, Adamis AP, Cunningham ET. Jr, Feinsod M, Guyer DR. Pegaptanib for neovascular age-related macular degeneration. N. Engl. J. Med. 351(27), 2805–2816 (2004).
   PubMed Web of Science ®Google Scholar
• Rosenfeld PJ, Brown DM, Heier JS et al. Ranibizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 355(14), 1419–1431 (2006).
   PubMed Web of Science ®Google Scholar
• Brown DM, Kaiser PK, Michels M et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N. Engl. J. Med. 355(14), 1432–1444 (2006).
   PubMed Web of Science ®Google Scholar
• Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology 116(1), 57–65 e55 (2009).
   PubMed Web of Science ®Google Scholar
• Chen Y, Wiesmann C, Fuh G et al. Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen. J. Mol. Biol. 293(4), 865–881 (1999).
   PubMed Web of Science ®Google Scholar
• Krzystolik MG, Afshari MA, Adamis AP et al. Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch. Ophthalmol. 120(3), 338–346 (2002).
   PubMed Web of Science ®Google Scholar
• Martin DF, Maguire MG, Ying GS et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. The CATT Research Group. N. Engl. J. Med. 364(20), 1897–1908 (2011).
   PubMed Web of Science ®Google Scholar
• Stewart MW, Grippon S, Kirkpatrick P. Aflibercept. Nat. Rev. Drug Discov. 11(4), 269–270 (2012).
   PubMed Web of Science ®Google Scholar
• Allergan and Molecular Partners enter into a license agreement for MP0112. (2011).
   Google Scholar
• Souied EH, Mauget-Faysse M, Devin F et al.; Mp0112 Wet Amd Study Group. Phase I MP0112 Wet AMD Study Imaging Results: Darpin® MP0112 Shows Potential For Quarterly Dosing In Wet AMD. 2011 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO 2011), Fort Lauderdale, FL, USA, 1–5 May 2011 (Poster 3541/A339).
   Google Scholar
• Wolf S, Souied EH, Mauget-Faysse M et al.; Mp0112 Wet Amd Study Group. Phase I Mp0112 Wet AMD Study: Results Of A Single Escalating Dose Study With DARPin® MP0112 In Wet AMD. 2011 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO 2011), Fort Lauderdale, FL, USA, 1–5 May 2011 (Poster 1655).
   Google Scholar
• Research and Markets: Stakeholder Opinions: Ophthalmology. Business Wire, 11th August (2010).
   Google Scholar
• Benjamin LE, Hemo I, Keshet E. A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 125(9), 1591–1598 (1998).
   PubMed Web of Science ®Google Scholar
• Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J. Clin. Invest. 111(9), 1287–1295 (2003).
   PubMed Web of Science ®Google Scholar
• Erber R, Thurnher A, Katsen AD et al. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J. 18(2), 338–340 (2004).
   PubMed Web of Science ®Google Scholar
• Ferrara N, Gerber HP, Lecouter J. The biology of VEGF and its receptors. Nat. Med. 9(6), 669–676 (2003).
   PubMed Web of Science ®Google Scholar
• Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13(1), 9–22 (1999).
   PubMed Web of Science ®Google Scholar
• Otrock ZK, Makarem JA, Shamseddine AI. Vascular endothelial growth factor family of ligands and receptors: review. Blood Cells Mol. Dis. 38(3), 258–268 (2007).
   PubMed Web of Science ®Google Scholar
• Zachary I, Gliki G. Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc. Res. 49(3), 568–581 (2001).
   PubMed Web of Science ®Google Scholar
• Alvarez RH, Kantarjian HM, Cortes JE. Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin. Proc. 81(9), 1241–1257 (2006).
   PubMed Web of Science ®Google Scholar
• Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol. Rev. 79(4), 1283–1316 (1999).
   PubMed Web of Science ®Google Scholar
• Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 22(10), 1276–1312 (2008).
   PubMed Web of Science ®Google Scholar
• Karkkainen MJ, Makinen T, Alitalo K. Lymphatic endothelium: a new frontier of metastasis research. Nat. Cell Biol. 4(1), E2–E5 (2002).
   PubMed Web of Science ®Google Scholar
• Carmeliet P, Ferreira V, Breier G et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380(6573), 435–439 (1996).
   PubMed Web of Science ®Google Scholar
• Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol. Endocrinol. 5(12), 1806–1814 (1991).
   PubMed Web of Science ®Google Scholar
• Tischer E, Mitchell R, Hartman T et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J. Biol. Chem. 266(18), 11947–11954 (1991).
   PubMed Web of Science ®Google Scholar
• Maharaj AS, Saint-Geniez M, Maldonado AE, D’amore PA. Vascular endothelial growth factor localization in the adult. Am. J. Pathol. 168(2), 639–648 (2006).
   PubMed Web of Science ®Google Scholar
• Shalaby F, Rossant J, Yamaguchi TP et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376(6535), 62–66 (1995).
   PubMed Web of Science ®Google Scholar
• Semenza GL. HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J. Appl. Physiol. 88(4), 1474–1480 (2000).
   PubMed Web of Science ®Google Scholar
• Li X, Ponten A, Aase K et al. PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. Nat. Cell Biol. 2(5), 302–309 (2000).
   PubMed Web of Science ®Google Scholar
• Larochelle WJ, Jeffers M, Mcdonald WF et al. PDGF-D, a new protease-activated growth factor. Nat. Cell Biol. 3(5), 517–521 (2001).
   PubMed Web of Science ®Google Scholar
• Bergsten E, Uutela M, Li X et al. PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat. Cell Biol. 3(5), 512–516 (2001).
   PubMed Web of Science ®Google Scholar
• Vassbotn FS, Havnen OK, Heldin CH, Holmsen H. Negative feedback regulation of human platelets via autocrine activation of the platelet-derived growth factor alpha-receptor. J. Biol. Chem. 269(19), 13874–13879 (1994).
   PubMed Web of Science ®Google Scholar
• Hart CE, Forstrom JW, Kelly JD et al. Two classes of PDGF receptor recognize different isoforms of PDGF. Science 240(4858), 1529–1531 (1988).
   PubMed Web of Science ®Google Scholar
• Heldin CH, Backstrom G, Ostman A et al. Binding of different dimeric forms of PDGF to human fibroblasts: evidence for two separate receptor types. Embo J. 7(5), 1387–1393 (1988).
   PubMed Web of Science ®Google Scholar
• Hoch RV, Soriano P. Roles of PDGF in animal development. Development 130(20), 4769–4784 (2003).
   PubMed Web of Science ®Google Scholar
• Kazlauskas A, Cooper JA. Phosphorylation of the PDGF receptor beta subunit creates a tight binding site for phosphatidylinositol 3 kinase. Embo J. 9(10), 3279–3286 (1990).
   PubMed Web of Science ®Google Scholar
• Vanhaesebroeck B, Leevers SJ, Panayotou G, Waterfield MD. Phosphoinositide 3-kinases: a conserved family of signal transducers. Trends Biochem. Sci. 22(7), 267–272 (1997).
   PubMed Web of Science ®Google Scholar
• Bos JL. Ras-like GTPases. Biochim. Biophys. Acta 1333(2), M19–M31 (1997).
   Web of Science ®Google Scholar
• Lowenstein EJ, Daly RJ, Batzer AG et al. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell 70(3), 431–442 (1992).
   PubMed Web of Science ®Google Scholar
• Kaplan DR, Morrison DK, Wong G, Mccormick F, Williams LT. PDGF beta-receptor stimulates tyrosine phosphorylation of GAP and association of GAP with a signaling complex. Cell 61(1), 125–133 (1990).
   PubMed Web of Science ®Google Scholar
• Valius M, Kazlauskas A. Phospholipase C-gamma 1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor’s mitogenic signal. Cell 73(2), 321–334 (1993).
   PubMed Web of Science ®Google Scholar
• Lindahl P, Johansson BR, Leveen P, Betsholtz C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277(5323), 242–245 (1997).
   PubMed Web of Science ®Google Scholar
• Robbins SG, Mixon RN, Wilson DJ et al. Platelet-derived growth factor ligands and receptors immunolocalized in proliferative retinal diseases. Invest. Ophthalmol. Vis. Sci. 35(10), 3649–3663 (1994).
   PubMed Web of Science ®Google Scholar
• Provis JM, Leech J, Diaz CM, Penfold PL, Stone J, Keshet E. Development of the human retinal vasculature: cellular relations and VEGF expression. Exp. Eye Res. 65(4), 555–568 (1997).
   PubMed Web of Science ®Google Scholar
• Gariano RF, Gardner TW. Retinal angiogenesis in development and disease. Nature 438(7070), 960–966 (2005).
   PubMed Web of Science ®Google Scholar
• Hoffmann S, He S, Ehren M, Ryan SJ, Wiedemann P, Hinton DR. MMP-2 and MMP-9 secretion by rpe is stimulated by angiogenic molecules found in choroidal neovascular membranes. Retina 26(4), 454–461 (2006).
   PubMed Web of Science ®Google Scholar
• Steen B, Sejersen S, Berglin L, Seregard S, Kvanta A. Matrix metalloproteinases and metalloproteinase inhibitors in choroidal neovascular membranes. Invest. Ophthalmol. Vis. Sci. 39(11), 2194–2200 (1998).
   PubMed Web of Science ®Google Scholar
• Grossniklaus HE, Ling JX, Wallace TM et al. Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization. Mol. Vis. 8, 119–126 (2002).
   PubMed Web of Science ®Google Scholar
• Otani A, Takagi H, Oh H, Koyama S, Matsumura M, Honda Y. Expressions of angiopoietins and Tie2 in human choroidal neovascular membranes. Invest. Ophthalmol. Vis. Sci. 40(9), 1912–1920 (1999).
   PubMed Web of Science ®Google Scholar
• Nagai N, Oike Y, Izumi-Nagai K et al. Angiotensin II type 1 receptor-mediated inflammation is required for choroidal neovascularization. Arterioscler. Thromb. Vasc. Biol. 26(10), 2252–2259 (2006).
   PubMed Web of Science ®Google Scholar
• Ng EWM, Adamis AP. Anti-VEGF aptamer (pegaptanib) therapy for ocular vascular diseases. Ann. NY Acad. Sci. 1082, 151–171 (2006).
   PubMed Web of Science ®Google Scholar
• Homsi J, Daud AI. Spectrum of activity and mechanism of action of VEGF/PDGF inhibitors. Cancer Control 14(3), 285–294 (2007).
   PubMedGoogle Scholar
• Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359(4), 378–390 (2008).
   PubMed Web of Science ®Google Scholar
• Perez-Santonja JJ, Campos-Mollo E, Lledo-Riquelme M, Javaloy J, Alio JL. Inhibition of corneal neovascularization by topical bevacizumab (Anti-VEGF) and sunitinib (Anti-VEGF and Anti-PDGF) in an animal model. Am. J. Ophthalmol. 150(4), 519–528 e511 (2010).
   PubMed Web of Science ®Google Scholar
• Chung EJ, Yoo S, Lim HJ, Byeon SH, Lee JH, Koh HJ. Inhibition of choroidal neovascularisation in mice by systemic administration of the multikinase inhibitor, sorafenib. Br. J. Ophthalmol. 93(7), 958–963 (2009).
   PubMed Web of Science ®Google Scholar
• Takahashi K, Saishin Y, King AG, Levin R, Campochiaro PA. Suppression and regression of choroidal neovascularization by the multitargeted kinase inhibitor pazopanib. Arch. Ophthalmol. 127(4), 494–499 (2009).
   PubMedGoogle Scholar
• D.S. Boyer Oa-PIaSGO, Retina Vitreous Assoc Med Group, Los Angeles, Ca. combined inhibition of platelet derived (PDGF) and vascular endothelial (VEGF) growth factors for the treatment of neovascular age-related macular degeneration (NV-AMD) - results of a phase 1 study (2009).
   Google Scholar
• Jo N, Mailhos C, Ju M et al. Inhibition of platelet-derived growth factor B signaling enhances the efficacy of anti-vascular endothelial growth factor therapy in multiple models of ocular neovascularization. Am. J. Pathol. 168(6), 2036–2053 (2006).
   PubMed Web of Science ®Google Scholar
• Mendel DB, Laird AD, Xin X et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin. Cancer Res. 9(1), 327–337 (2003).
   PubMed Web of Science ®Google Scholar
• FDA approves new treatment for gastrointestinal and kidney cancer. FDA Press Release, 26th January (2006).
   Google Scholar
• FDA approves Sutent for rare type of pancreatic cancer. FDA Press Release, 20th May (2011).
   Google Scholar
• Sternberg CN, Davis ID, Mardiak J et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J. Clin. Oncol. 28(6), 1061–1068 (2010).
   PubMed Web of Science ®Google Scholar
• FDA approves Votrient® for treatment of patients with certain types of advanced soft tissue sarcoma. PR Newswire, 26th April (2012).
   Google Scholar
• Ferrara N, Mass RD, Campa C, Kim R. Targeting VEGF-A to treat cancer and age-related macular degeneration. Annu. Rev. Med. 58, 491–504 (2007).
   PubMed Web of Science ®Google Scholar
• Akiyama H, Kachi S, Silva RL et al. Intraocular injection of an aptamer that binds PDGF-B: a potential treatment for proliferative retinopathies. J. Cell Physiol. 207(2), 407–412 (2006).
   PubMed Web of Science ®Google Scholar
• Saika S, Kono-Saika S, Tanaka T et al. Smad3 is required for dedifferentiation of retinal pigment epithelium following retinal detachment in mice. Lab. Invest. 84(10), 1245–1258 (2004).
   PubMed Web of Science ®Google Scholar
• Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 356(2), 125–134 (2007).
   PubMed Web of Science ®Google Scholar
• Diago T, Pulido JS, Molina JR, Collett LC, Link TP, Ryan EH. Jr. Ranibizumab combined with low-dose sorafenib for exudative age-related macular degeneration. Mayo Clin. Proc. 83(2), 231–234 (2008).
   PubMed Web of Science ®Google Scholar
• Slakter JS, Tolentino MJ, Berger BB et al. A phase I/II study of oral pazopanib, a receptor tyrosine kinase inhibitor, in neovascular age related macular degeneration. Presented at: ARVO 2012 Annual Meeting Abstracts, Fort Lauderdale, FL, USA, 7 May 2012 (Abstract D1056).
   Google Scholar
• Ophthotech’s novel anti-PDGF combination agent fovista™ demonstrated superior efficacy over lucentis® monotherapy in large controlled wet AMD trial. Business Wire 13th June (2012).
   Google Scholar
• Xcovery Holdings Raises $6M in Series B Financing; Xcovery Vision Set to Begin Phase I/II Macular Degeneration Trial with its Oral Drug Candidate. Xcovery Holdings, 19th September (2012).
   Google Scholar
• Moore KN, Jones SF, Kurkjian C et al. Phase I, first-in-human trial of an oral VEGFR tyrosine kinase inhibitor (TKI) x-82 in patients (pts) with advanced solid tumors. J. Clin. Oncol. 30 (Suppl.), Abstract 3041 (2012).
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Hutson TE, Tomczak P et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N. Engl. J. Med. 356(2), 115–124 (2007).
   PubMed Web of Science ®Google Scholar
• Demetri GD, Van Oosterom AT, Garrett CR et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368(9544), 1329–1338 (2006).
   PubMed Web of Science ®Google Scholar
• Rakic JM, Lambert V, Devy L et al. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 44(7), 3186–3193 (2003).
   PubMed Web of Science ®Google Scholar
• Rosenthal R, Wohlleben H, Malek G et al. Insulin-like growth factor-1 contributes to neovascularization in age-related macular degeneration. Biochem. Biophys. Res. Commun. 323(4), 1203–1208 (2004).
   PubMed Web of Science ®Google Scholar
• Dawson DW, Volpert OV, Gillis P et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 285(5425), 245–248 (1999).
   PubMed Web of Science ®Google Scholar
• Mori K, Duh E, Gehlbach P et al. Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization. J. Cell Physiol. 188(2), 253–263 (2001).
   PubMed Web of Science ®Google Scholar
• Campochiaro PA, Nguyen QD, Shah SM et al. Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: results of a phase I clinical trial. Hum. Gene Ther. 17(2), 167–176 (2006).
   PubMed Web of Science ®Google Scholar
• Heier JS, Brown DM, Chong V et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119(12), 2537–2548 (2012).
   PubMed Web of Science ®Google Scholar