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Experimental Diabetes Research
Volume 2012 (2012), Article ID 728325, 8 pages
http://dx.doi.org/10.1155/2012/728325
Review Article

The Role of Angiogenesis in the Development of Proliferative Diabetic Retinopathy: Impact of Intravitreal Anti-VEGF Treatment

1Department of Ophthalmology, Vita-Salute University, San Raffaele Scientific Institute, 20132 Milan, Italy
2Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, 20132 Milan, Italy

Received 17 November 2011; Revised 30 January 2012; Accepted 13 February 2012

Academic Editor: Johannes Waltenberger

Copyright © 2012 Gemma Tremolada et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. M. V. Narayan, J. P. Boyle, L. S. Geiss, J. B. Saaddine, and T. J. Thompson, “Impact of recent increase in incidence on future diabetes burden: U.S., 2005–2050,” Diabetes Care, vol. 29, no. 9, pp. 2114–2116, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. J. B. Saaddine, A. A. Honeycutt, K. M. V. Narayan, X. Zhang, R. Klein, and J. P. Boyle, “Projection of diabetic retinopathy and other major eye diseases among people with diabetes mellitus: United States, 2005–2050,” Archives of Ophthalmology, vol. 126, no. 12, pp. 1740–1747, 2008. View at Publisher · View at Google Scholar · View at Scopus
  3. D. S. Fong, L. Aiello, T. W. Gardner et al., “Retinopathy in Diabetes,” Diabetes Care, vol. 27, supplement 1, pp. S84–S87, 2004. View at Google Scholar
  4. X. Zhang, J. B. Saaddine, C. F. Chou et al., “Prevalence of diabetic retinopathy in the United States, 2005–2008,” JAMA - Journal of the American Medical Association, vol. 304, no. 6, pp. 649–656, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. R. Klein, M. D. Knudtson, K. E. Lee, R. Gangnon, and B. E. K. Klein, “The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXII. The twentyfive-year progression of retinopathy in persons with type 1 diabetes,” Ophthalmology, vol. 115, no. 11, pp. 1859–1868, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. P. Hovind, L. Tarnow, K. Rossing et al., “Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes,” Diabetes Care, vol. 26, no. 4, pp. 1258–1264, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Nordwall, M. Bojestig, H. J. Arnqvist, and J. Ludvigsson, “Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of Type 1 diabetes - The Linköping Diabetes Complications Study,” Diabetologia, vol. 47, no. 7, pp. 1266–1272, 2004. View at Google Scholar · View at Scopus
  8. G. A. Lutty, D. S. McLeod, C. Merges, A. Diggs, and J. Plouét, “Localization of vascular endothelial growth factor in human retina and choroid,” Archives of Ophthalmology, vol. 114, no. 8, pp. 971–977, 1996. View at Google Scholar · View at Scopus
  9. B. P. Nicholson and A. P. Schachat, “A review of clinical trials of anti-VEGF agents for diabetic retinopathy,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 248, no. 7, pp. 915–930, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. D. Shweiki, A. Itin, D. Soffer, and E. Keshet, “Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis,” Nature, vol. 359, no. 6398, pp. 843–845, 1992. View at Publisher · View at Google Scholar · View at Scopus
  11. J. W. Miller, A. P. Adamis, and L. P. Aiello, “Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy,” Diabetes/Metabolism Reviews, vol. 13, no. 1, pp. 37–50, 1997. View at Publisher · View at Google Scholar · View at Scopus
  12. L. P. Aiello, R. L. Avery, P. G. Arrigg et al., “Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders,” New England Journal of Medicine, vol. 331, no. 22, pp. 1480–1487, 1994. View at Publisher · View at Google Scholar · View at Scopus
  13. G. S. Robinson, E. A. Pierce, S. L. Rook, E. Foley, R. Webb, and L. E. H. Smith, “Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 10, pp. 4851–4856, 1996. View at Publisher · View at Google Scholar · View at Scopus
  14. M. J. Tolentino, D. S. McLeod, M. Taomoto, T. Otsuji, A. P. Adamis, and G. A. Lutty, “Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate,” American Journal of Ophthalmology, vol. 133, no. 3, pp. 373–385, 2002. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Lu, V. L. Perez, N. Ma et al., “VEGF increases retinal vascular ICAM-1 expression in vivo,” Investigative Ophthalmology and Visual Science, vol. 40, no. 8, pp. 1808–1812, 1999. View at Google Scholar · View at Scopus
  16. B. Barleon, S. Sozzani, D. Zhou, H. A. Weich, A. Mantovani, and D. Marmé, “Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1,” Blood, vol. 87, no. 8, pp. 3336–3343, 1996. View at Google Scholar · View at Scopus
  17. K. Miyamoto, S. Khosrof, S. E. Bursell et al., “Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 19, pp. 10836–10841, 1999. View at Publisher · View at Google Scholar · View at Scopus
  18. S. Ishida, T. Usui, K. Yamashiro et al., “VEGF164 is proinflammatory in the diabetic retina,” Investigative Ophthalmology and Visual Science, vol. 44, no. 5, pp. 2155–2162, 2003. View at Publisher · View at Google Scholar
  19. D. S. McLeod, D. J. Lefer, C. Merges, and G. A. Lutty, “Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid,” American Journal of Pathology, vol. 147, no. 3, pp. 642–653, 1995. View at Google Scholar · View at Scopus
  20. A. M. Joussen, V. Poulaki, W. Qin et al., “Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo,” American Journal of Pathology, vol. 160, no. 2, pp. 501–509, 2002. View at Google Scholar · View at Scopus
  21. J. F. Vander, J. S. Duker, W. E. Benson, G. C. Brown, J. A. McNamara, and R. B. Rosenstein, “Long-term stability and visual outcome after favorable initial response of proliferative diabetic retinopathy to panretinal photocoagulation,” Ophthalmology, vol. 98, no. 10, pp. 1575–1579, 1991. View at Google Scholar · View at Scopus
  22. A. J. Brucker, H. Qin, A. N. Antoszyk et al., “Observational study of the development of diabetic macular edema following panretinal (scatter) photocoagulation given in 1 or 4 sittings,” Archives of Ophthalmology, vol. 127, no. 2, pp. 132–140, 2009. View at Publisher · View at Google Scholar
  23. H. W. Flynn Jr., E. Y. Chew, B. D. Simons, F. B. Barton, N. A. Remaley, and F. L. Ferris, “Pars plana vitrectomy in the Early Treatment Diabetic Retinopathy Study: ETDRS report number 17,” Ophthalmology, vol. 99, no. 9, pp. 1351–1357, 1992. View at Google Scholar · View at Scopus
  24. A. Salam, R. Mathew, and S. Sivaprasad, “Treatment of proliferative diabetic retinopathy with anti-VEGF agents,” Acta Ophthalmologica, vol. 89, no. 5, pp. 405–411, 2011. View at Publisher · View at Google Scholar
  25. W. Abdallah and A. A. Fawzi, “Anti-VEGF therapy in proliferative diabetic retinopathy,” International Ophthalmology Clinics, vol. 49, no. 2, pp. 95–107, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Mirshahi, R. Roohipoor, A. Lashay, S. F. Mohammadi, A. Abdoallahi, and H. Faghihi, “Bevacizumab-augmented retinal laser photocoagulation in proliferative diabetic retinopathy: A randomized double-masked clinical trial,” European Journal of Ophthalmology, vol. 18, no. 2, pp. 263–269, 2008. View at Google Scholar · View at Scopus
  27. M. Tonello, R. A. Costa, F. P. P. Almeida, J. C. Barbosa, I. U. Scott, and R. Jorge, “Panretinal photocoagulation versus PRP plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy (IBeHi study),” Acta Ophthalmologica, vol. 86, no. 4, pp. 385–389, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Rizzo, F. Genovesi-Ebert, E. Bartolo, A. Vento, S. Miniaci, and G. Williams, “Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR),” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 246, no. 6, pp. 837–842, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. A. P. Adamis, J. W. Miller, M. T. Bernal et al., “Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy,” American Journal of Ophthalmology, vol. 118, no. 4, pp. 445–450, 1994. View at Google Scholar · View at Scopus
  30. W. B. Cho, S. B. Oh, J. W. Moon, and H. C. Kim, “Panretinal photocoagulation combined with intravitreal bevacizumab in high-risk proliferative diabetic retinopathy,” Retina, vol. 29, no. 4, pp. 516–522, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Mirshahi, R. Roohipoor, A. Lashay, S. F. Mohammadi, A. Abdoallahi, and H. Faghihi, “Bevacizumab-augmented retinal laser photocoagulation in proliferative diabetic retinopathy: A randomized double-masked clinical trial,” European Journal of Ophthalmology, vol. 18, no. 2, pp. 263–269, 2008. View at Google Scholar · View at Scopus
  32. R. Jorge, R. A. Costa, D. Calucci, L. P. Cintra, and I. U. Scott, “Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (Ibepe study),” Retina, vol. 26, no. 9, pp. 1006–1013, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Moradian, H. Ahmadieh, M. Malihi, M. Soheilian, M. H. Dehghan, and M. Azarmina, “Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 246, no. 12, pp. 1699–1705, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. J. F. Arevalo, M. Maia, H. W. Flynn et al., “Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy,” British Journal of Ophthalmology, vol. 92, no. 2, pp. 213–216, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. W. Abdallah and A. A. Fawzi, “Anti-VEGF therapy in proliferative diabetic retinopathy,” International Ophthalmology Clinics, vol. 49, no. 2, pp. 95–107, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. M. G. Krzystolik, T. Filippopoulos, J. F. Ducharme, and J. I. Loewenstein, “Pegaptanib as an adjunctive treatment for complicated neovascular diabetic retinopathy,” Archives of Ophthalmology, vol. 124, no. 6, pp. 920–921, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. P. T. Yeh, C. M. Yang, Y. C. Lin, M. S. Chen, and C. H. Yang, “Bevacizumab pretreatment in vitrectomy with silicone oil for severe diabetic retinopathy,” Retina, vol. 29, no. 6, pp. 768–774, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. H. Ahmadieh, N. Shoeibi, M. Entezari, and R. Monshizadeh, “Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients a randomized clinical trial,” Ophthalmology, vol. 116, no. 10, pp. 1943–1948, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. K. V. Chalam, S. K. Gupta, S. Grover, V. S. Brar, and S. Agarwal, “Intracameral Avastin dramatically resolves iris neovascularization and reverses neovascular glaucoma,” European Journal of Ophthalmology, vol. 18, no. 2, pp. 255–262, 2008. View at Google Scholar · View at Scopus
  40. C. Costagliola, U. Cipollone, M. Rinaldi, M. Della Corte, F. Semeraro, and M. R. Romano, “Intravitreal bevacizumab (Avastin®) injection for neovascular glaucoma: A survey on 23 cases throughout 12-month follow-up,” British Journal of Clinical Pharmacology, vol. 66, no. 5, pp. 667–750, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. T. H. Lim, S. H. Bae, Y. J. Cho, J. H. Lee, H. K. Kim, and Y. H. Sohn, “Concentration of vascular endothelial growth factor after intracameral bevacizumab injection in eyes with neovascular glaucoma,” Korean Journal of Ophthalmology, vol. 23, no. 3, pp. 188–192, 2009. View at Google Scholar · View at Scopus
  42. T. M. Eid, A. Radwan, W. El-Manawy, and I. El-Hawary, “Intravitreal bevacizumab and aqueous shunting surgery for neovascular glaucoma: safety and efficacy,” Canadian Journal of Ophthalmology, vol. 44, no. 4, pp. 451–456, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. R. A. Cheema, M. M. Al-Mubarak, Y. M. Amin, and M. A. Cheema, “Role of combined cataract surgery and intravitreal bevacizumab injection in preventing progression of diabetic retinopathy. Prospective randomized study,” Journal of Cataract and Refractive Surgery, vol. 35, no. 1, pp. 18–25, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. Y. Takamura, E. Kubo, and Y. Akagi, “Analysis of the effect of intravitreal bevacizumab injection on diabetic macular edema after cataract surgery,” Ophthalmology, vol. 116, no. 6, pp. 1151–1157, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Lanzagorta-Aresti, E. Palacios-Pozo, J. L. Menezo Rozalen, and A. Navea-Tejerina, “Prevention of vision loss after cataract surgery in diabetic macular edema with intravitreal bevacizumab: A pilot study,” Retina, vol. 29, no. 4, pp. 530–535, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. A. P. Adamis, M. Altaweel, N. M. Bressler et al., “Changes in retinal neovascularization after pegaptanib (Macugen) therapy in diabetic individuals,” Ophthalmology, vol. 113, no. 1, pp. 23–28, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. V. H. González, G. P. Giuliari, R. M. Banda, and D. A. Guel, “Intravitreal injection of pegaptanib sodium for proliferative diabetic retinopathy,” British Journal of Ophthalmology, vol. 93, no. 11, pp. 1474–1478, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. M. S. R. Jardeleza and J. W. Miller, “Review of anti-vEGF therapy in proliferative diabetic retinopathy,” Seminars in Ophthalmology, vol. 24, no. 2, pp. 87–92, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. Y. Saishin, Y. Saishin, K. Takahashi et al., “VEGF-TRAPR1R2 suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier,” Journal of Cellular Physiology, vol. 195, no. 2, pp. 241–248, 2003. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Ishida, T. Usui, K. Yamashiro et al., “VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization,” Journal of Experimental Medicine, vol. 198, no. 3, pp. 483–489, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Shen, R. Samul, R. L. Silva et al., “Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1,” Gene Therapy, vol. 13, no. 3, pp. 225–234, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. W. Abdallah and A. A. Fawzi, “Anti-VEGF therapy in proliferative diabetic retinopathy,” International Ophthalmology Clinics, vol. 49, no. 2, pp. 95–107, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Brownlee, “The pathobiology of diabetic complications: A unifying mechanism,” Diabetes, vol. 54, no. 6, pp. 1615–1625, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. R. L. Avery, “Regression of retinal and iris neovascularization after intravitreal bevacizumab (avastin) treatment,” Retina, vol. 26, no. 3, pp. 352–354, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. R. F. Spaide and Y. L. Fisher, “Intravitreal bevacizumab (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage,” Retina, vol. 26, no. 3, pp. 275–278, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. M. Thew, “Rapid resolution of severe retinal neovascularisation in proliferative diabetic retinopathy following adjunctive intravitreal bevacizumab (Avastin),” Clinical and Experimental Optometry, vol. 92, no. 1, pp. 34–37, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. A. M. Minnella, C. M. Savastano, L. Ziccardi et al., “Intravitreal bevacizumab (Avastin®) in proliferative diabetic retinopathy,” Acta Ophthalmologica, vol. 86, no. 6, pp. 683–687, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. G. Schmidinger, N. Maar, M. Bolz, C. Scholda, and U. Schmidt-Erfurth, “Repeated intravitreal bevacizumab (Avastin) treatment of persistent new vessels in proliferative diabetic retinopathy after complete panretinal photocoagulation,” Acta Ophthalmologica, vol. 89, no. 1, pp. 76–81, 2011. View at Publisher · View at Google Scholar
  59. M. E. Torres-Soriano, E. Reyna-Castelán, and M. Hernández-Rojas, “Tractional retinal detachment after intravitreal injection of bevacizumab in proliferative diabetic retinopathy,” Retinal Cases & Brief Reports, vol. 3, no. 1, pp. 70–73, 2009. View at Google Scholar
  60. E. J. Kuiper, F. A. Van Nieuwenhoven, M. D. de Smet et al., “The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy,” PLoS One, vol. 3, no. 7, Article ID e2675, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. P. T. Yeh, C. M. Yang, Y. C. Lin, M. S. Chen, and C. H. Yang, “Bevacizumab pretreatment in vitrectomy with silicone oil for severe diabetic retinopathy,” Retina, vol. 29, no. 6, pp. 768–774, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. J. B. Jonas, M. Schmidbauer, and F. Rensch, “Progression of tractional retinal detachment following intravitreal bevacizumab,” Acta Ophthalmologica, vol. 87, no. 5, pp. 571–572, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. J. F. Arevalo, M. Maia, H. W. Flynn Jr. et al., “Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy,” British Journal of Ophthalmology, vol. 92, no. 2, pp. 213–216, 2008. View at Publisher · View at Google Scholar
  64. P. Tranos, M. Gemenetzi, A. Papandroudis, C. Chrisafis, and D. Papadakos, “Progression of diabetic tractional retinal detachment following single injection of intravitreal Avastin,” Eye, vol. 22, no. 6, p. 862, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Jalil, C. Fenerty, and S. Charles, “Intravitreal bevacizumab (Avastin) causing acute glaucoma: an unreported complication,” Eye, vol. 21, no. 12, p. 1541, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. S. Jun Lee and H. Jun Koh, “Enlargement of the foveal avascular zone in diabetic retinopathy after adjunctive intravitreal bevacizumab (Avastin) with pars plana vitrectomy,” Journal of Ocular Pharmacology and Therapeutics, vol. 25, no. 2, pp. 173–174, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. E. S. Gragoudas, A. P. Adamis, E. T. Cunningham, M. Feinsod, and D. R. Guyer, “Pegaptanib for neovascular age-related macular degeneration,” New England Journal of Medicine, vol. 351, no. 27, pp. 2805–2816, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. D. B. Roth, A. King, M. Weiss, and D. Klein, “Systemic adverse events after bevacizumab,” Ophthalmology, vol. 116, no. 6, pp. 1226–1226.e1, 2009. View at Publisher · View at Google Scholar · View at Scopus
  69. V. Kumar, B. Ghosh, U. K. Raina, and N. Goel, “Efficacy and safety of one intravitreal injection of bevacizumab in diabetic macular oedema,” Acta Ophthalmologica, vol. 88, no. 2, p. e3, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. L. Wu, M. A. Martínez-Castellanos, H. Quiroz-Mercado et al., “Twelve-month safety of intravitreal injections of bevacizumab (Avastin): results of the pan-american collaborative retina study group (PACORES),” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 246, no. 1, pp. 81–87, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. J. O. Mason III, M. F. White, R. M. Feist et al., “Incidence of acute onset endophthalmitis following intravitreal bevacizumab (Avastin) injection,” Retina, vol. 28, no. 4, pp. 564–567, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. J. C. Yang, L. Haworth, R. M. Sherry et al., “A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer,” New England Journal of Medicine, vol. 349, no. 5, pp. 427–434, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. H. Hurwitz, L. Fehrenbacher, W. Novotny et al., “Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer,” New England Journal of Medicine, vol. 350, no. 23, pp. 2335–2342, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. D. J. D'Amico, “Pegaptanib sodium for neovascular age-related macular degeneration. Two-year safety results of the two prospective, multicenter, controlled clinical trials,” Ophthalmology, vol. 113, no. 6, pp. 992–1001.e6, 2006. View at Publisher · View at Google Scholar
  75. L. J. Singerman, H. Masonson, M. Patel et al., “Pegaptanib sodium for neovascular age-related macular degeneration: Third-year safety results of the VEGF inhibition study in ocular neovascularisation (VISION) trial,” British Journal of Ophthalmology, vol. 92, no. 12, pp. 1606–1611, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. P. J. Rosenfeld, D. M. Brown, J. S. Heier et al., “Ranibizumab for neovascular age-related macular degeneration,” New England Journal of Medicine, vol. 355, no. 14, pp. 1419–1431, 2006. View at Publisher · View at Google Scholar
  77. “Lucentis (Ranibizumab injection) Package Insert,” Genentech Corporation.
  78. M. S. R. Jardeleza and J. W. Miller, “Review of anti-vEGF therapy in proliferative diabetic retinopathy,” Seminars in Ophthalmology, vol. 24, no. 2, pp. 87–92, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. C. R. De Almodovar, D. Lambrechts, M. Mazzone, and P. Carmeliet, “Role and therapeutic potential of VEGF in the nervous system,” Physiological Reviews, vol. 89, no. 2, pp. 607–648, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. K. Nishijima, Y. S. Ng, L. Zhong et al., “Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury,” American Journal of Pathology, vol. 171, no. 1, pp. 53–67, 2007. View at Publisher · View at Google Scholar · View at Scopus