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Combination Therapy with Ocular Photodynamic Therapy for Age-Related Macular Degeneration

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Age-related Macular Degeneration Diagnosis and Treatment

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Abstract

Exudative AMD is the leading cause of blindness in people over 50 years old in the Western world. Choroidal neovascularization found in exudative AMD appears to be a multifactoral process involving inflammatory, vascular, and angiogenic components. Commercially available treatments for exudative AMD primarily target a solitary component of this multifactoral disease. Combining various treatment modalities for exudative AMD targets multiple components of choroidal neovascularization and has the potential for improving efficacy and reducing treatment frequency.

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References

  1. Rubin GS, Roche KB, Prasada-Rao P, Fried LP. Visual impairment and disability in older adults. Optom Vis Sci. 1994;71:750–60.

    Article  PubMed  CAS  Google Scholar 

  2. Williams RA, Brody BL, Thomas RG, Kaplan RM, Brown SI. The psychosocial impact of macular degeneration. Arch Ophthalmol. 1998;116:514–20.

    PubMed  CAS  Google Scholar 

  3. Friedman DS, O’Colmain BJ, Munoz B, et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122:564–72.

    Article  PubMed  Google Scholar 

  4. Kourlas H, Abrams P. Ranibizumab for the treatment of neovascular age-related macular degeneration: a review. Clin Ther. 2007;29:1850–61.

    Article  PubMed  CAS  Google Scholar 

  5. Pauleikhoff D. Neovascular age-related macular degeneration: natural history and treatment outcomes. Retina. 2005;25:1065–84.

    Article  PubMed  Google Scholar 

  6. Kaiser PK. Verteporfin photodynamic therapy and anti-angiogenic drugs: potential for combination therapy in exudative age-related macular degeneration. Cur Med Res Opin. 2007;23:477–87.

    Article  CAS  Google Scholar 

  7. Kent D, Sheridan C. Choroidal neovascularization: a wound healing perspective. Mol Vis. 2003;9:747–55.

    PubMed  CAS  Google Scholar 

  8. Zarbin MA. Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol. 2004;122:598–614.

    Article  PubMed  Google Scholar 

  9. Gille J. Antiangiogenic cancer therapies get their act together: current developments and future prospects of growth factor- and growth factor receptor-targeted approaches. Exp Dermatol. 2006;15:175–86.

    Article  PubMed  CAS  Google Scholar 

  10. Caprioni F, Fornarini G. Bevacizumab in the treatment of metastatic colorectal cancer. Future Oncol. 2007;3:141–8.

    Article  PubMed  CAS  Google Scholar 

  11. Giaccone G. The potential of antiangiogenic therapy in non-small cell lung cancer. Clin Cancer Res. 2007;13:1961–70.

    Article  PubMed  CAS  Google Scholar 

  12. Mancuso A, Calabro F, Sternberg CN. Current therapies and advances in the treatment of pancreatic cancer. Crit Rev Oncol Hematol. 2006;58:231–41.

    Article  PubMed  Google Scholar 

  13. Han ES, Monk BJ. Bevacizumab in the treatment of ovarian cancer. Expert Rev Anticancer Ther. 2007;7:1339–45.

    Article  PubMed  CAS  Google Scholar 

  14. Taiwo BO. Antiretroviral treatment: current approach and future prospects. Afr J Med Med Sci. 2006;35:S1–11.

    Google Scholar 

  15. Sturmer M, Staszewski S, Doerr HW. Quadruple nucleoside therapy with zidovudine, lamivudine, abacavir and tenofovir in the treatment of HIV. Antivir Ther. 2007;12:695–703.

    PubMed  Google Scholar 

  16. Weir MR. Risk-based classification of hypertension and the role of combination therapy. J Clin Hypertens (Greenwich). 2008;10:4–12.

    Article  Google Scholar 

  17. Elliott WJ. What factors contribute to the inadequate control of elevated blood pressure? J Clin Hypertens (Greenwich). 2008;10:20–6.

    Article  Google Scholar 

  18. Klein R, Klein BE, Jensen SC, et al. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 1997;104:7–21.

    PubMed  CAS  Google Scholar 

  19. Pe’er J, Shweiki D, Itin A, et al. Hypoxia-induced expression of vascular endothelial growth factor by retinal cells is a common factor in neovascularizing ocular diseases. Lab Invest. 1995;72:638–45.

    PubMed  Google Scholar 

  20. Grunwald JE, Metelitsina TI, Dupont JC, et al. Reduced foveolar choroidal blood flow in eyes with increasing AMD severity. Invest Ophthalmol Vis Sci. 2005;46:1033–8.

    Article  PubMed  Google Scholar 

  21. Yoshida S, Yoshida A, Ishibashi T. Induction of IL-8, MCP-1, and bFGF by TNF-alpha in retinal glial cells: implications for retinal neovascularization during post-ischemic inflammation. Graefes Arch Clin Exp Ophthalmol. 2004;242:409–13.

    Article  PubMed  CAS  Google Scholar 

  22. Spaide RF. Rationale for combination therapies for choroidal neovascularization. Am J Ophthalmol. 2006;141:149–56.

    Article  PubMed  Google Scholar 

  23. Campochiaro PA. Ocular neovascularisation and excessive vascular permeability. Expert Opin Biol Ther. 2004;4:1395–402.

    Article  PubMed  CAS  Google Scholar 

  24. Shima DT, Adamis AP, Ferrara N, et al. Hypoxic induction of endothelial cell growth factors in retinal cells: identification and characterization of vascular endothelial growth factor (VEGF) as the mitogen. Mol Med. 1995;1:182–93.

    PubMed  CAS  Google Scholar 

  25. Keyt BA, Berleau LT, Nguyen HV, et al. The carboxyl-terminal domain (111–165) of vascular endothelial growth factor is critical for its mitogenic potency. J Biol Chem. 1996;271:7788–95.

    Article  PubMed  CAS  Google Scholar 

  26. Park JE, Keller GA, Ferrara N. The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell. 1993;4:1317–26.

    PubMed  CAS  Google Scholar 

  27. Ng EW, Adamis AP. Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration. Can J Ophthalmol. 2005;40:352–68.

    PubMed  Google Scholar 

  28. Shima DT, Kuroki M, Deutsch U, et al. The mouse gene for vascular endothelial growth factor. Genomic structure, definition of the transcriptional unit, and characterization of transcriptional and post-­transcriptional regulatory sequences. J Biol Chem. 1996;271:3877–83.

    Article  PubMed  CAS  Google Scholar 

  29. Ishida S, Usui T, Yamashiro K, et al. VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization. J Exp Med. 2003;198:483–9.

    Article  PubMed  CAS  Google Scholar 

  30. McColm JR, Geisen P, Hartnett ME. VEGF isoforms and their expression after a single episode of hypoxia or repeated fluctuations between hyperoxia and hypoxia: relevance to clinical ROP. Mol Vis. 2004;10:512–20.

    PubMed  CAS  Google Scholar 

  31. Hiromatsu Y, Toda S. Mast cells and angiogenesis. Microsc Res Tech. 2003;60:64–9.

    Article  PubMed  Google Scholar 

  32. Miyamoto K, Khosrof S, Bursell SE, et al. Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability is mediated by intercellular adhesion molecule-1 (ICAM-1). Am J Pathol. 2000;156:1733–9.

    Article  PubMed  CAS  Google Scholar 

  33. Cursiefen C, Chen L, Borges LP, et al. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest. 2004;113:1040–50.

    PubMed  CAS  Google Scholar 

  34. 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. 1995;92:10457–61.

    Article  PubMed  CAS  Google Scholar 

  35. Krzystolik MG, Afshari MA, Adamis AP, et al. Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch Ophthalmol. 2002;120:338–46.

    PubMed  CAS  Google Scholar 

  36. 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. 1994;331:1480–7.

    Article  PubMed  CAS  Google Scholar 

  37. Malecaze F, Clamens S, Simorre-Pinatel V, et al. Detection of vascular endothelial growth factor messenger RNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophthalmol. 1994;112:1476–82.

    PubMed  CAS  Google Scholar 

  38. Schwesinger C, Yee C, Rohan RM, et al. Intrac­horoidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium. Am J Pathol. 2001;158:1161–72.

    Article  PubMed  CAS  Google Scholar 

  39. Tolentino MJ, Miller JW, Gragoudas ES, et al. Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primate. Arch Ophthalmol. 1996;114:964–70.

    PubMed  CAS  Google Scholar 

  40. Tolentino MJ, McLeod DS, Taomoto M, et al. Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate. Am J Ophthalmol. 2002;133:373–85.

    Article  PubMed  CAS  Google Scholar 

  41. He S, Jin ML, Worpel V, Hinton DR. A role for connective tissue growth factor in the pathogenesis of choroidal neovascularization. Arch Ophthalmol. 2003;121:1283–8.

    Article  PubMed  CAS  Google Scholar 

  42. Kliffen M, Sharma HS, Mooy CM, et al. Increased expression of angiogenic growth factors in age-­related maculopathy. Br J Ophthalmol. 1997;81:154–62.

    Article  PubMed  CAS  Google Scholar 

  43. Holekamp NM, Bouck N, Volpert O. Pigment epithelium derived factor is deficient in the vitreous of patients with choroidal neovascularization due to age-related macular degeneration. Am J Ophthalmol. 2002;134:220–7.

    Article  PubMed  CAS  Google Scholar 

  44. Kaiser PK. Verteporfin therapy in combination with triamcinolone: published studies investigating a potential synergistic effect. Curr Med Res Opin. 2005;21:705–13.

    Article  PubMed  CAS  Google Scholar 

  45. Schmidt-Erfurth U, Schlotzer-Schrehard U, Cursiefen C, et al. Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2003;44:4473–80.

    Article  PubMed  Google Scholar 

  46. Kaiser PK. Steroids for choroidal neovascularization. Am J Ophthalmol. 2005;139:533–5.

    Article  PubMed  Google Scholar 

  47. Bandi N, Kompella UB. Budesonide reduces vascular endothelial growth factor secretion and expression in airway (Calu-1) and alveolar (A549) epithelial cells. Eur J Pharmacol. 2001;425:109–16.

    Article  PubMed  CAS  Google Scholar 

  48. Folkman J. Ingber DE Angiostatic steroids. Method of discovery and mechanism of action. Ann Surg. 1987;206:374–83.

    Article  PubMed  CAS  Google Scholar 

  49. Tatar O, Shinoda K, Kaiserling E, et al. Early effects of triamcinolone on vascular endothelial growth factor and endostatin in human choroidal neovascularization. Arch Ophthalmol. 2008;126:193–9.

    Article  PubMed  CAS  Google Scholar 

  50. Wang YS, Friedrichs U, Eichler W, Hoffmann S, Wiedemann P. Inhibitory effects of triamcinolone acetonide on bFGF-induced migration and tube formation in choroidal microvascular endothelial cells. Graefes Arch Clin Exp Ophthalmol. 2002;240:42–8.

    Article  PubMed  CAS  Google Scholar 

  51. Fischer S, Renz D, Schaper W, Karliczek GF. In vitro effects of dexamethasone on hypoxia-induced hyperpermeability and expression of vascular endothelial growth factor. Eur J Pharmacol. 2001;411:231–43.

    Article  PubMed  CAS  Google Scholar 

  52. Ingber DE, Madri JA, Folkman J. A possible mechanism for inhibition of angiogenesis by angiostatic steroids: induction of capillary basement membrane dissolution. Endocrinology. 1986;119:1768–75.

    Article  PubMed  CAS  Google Scholar 

  53. Penfold PL, Wen L, Madigan MC, Gillies MC, King NJ, Provis JM. Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular degeneration. Clin Exp Immunol. 2000;121:458–65.

    Article  PubMed  CAS  Google Scholar 

  54. Penfold PL, Wen L, Madigan MC, King NJ, Provis JM. Modulation of permeability and adhesion molecule expression by human choroidal endothelial cells. Invest Ophthalmol Vis Sci. 2002;43:3125–30.

    PubMed  Google Scholar 

  55. Lewis GD, Campbell WB, Johnson AR. Inhibition of prostaglandin synthesis by glucocorticoids in human endothelial cells. Endocrinology. 1986;119:62–9.

    Article  PubMed  CAS  Google Scholar 

  56. Umland SP, Nahrebne DK, Razac S, et al. The inhibitory effects of topically active glucocorticoids on IL-4, IL-5, and interferon-gamma production by cultured primary CD4+ T cells. J Allergy Clin Immunol. 1997;100:511–9.

    Article  PubMed  CAS  Google Scholar 

  57. Bhattacherjee P, Williams RN, Eakins KE. A comparison of the ocular anti-inflammatory activity of steroidal and nonsteroidal compounds in the rat. Invest Ophthalmol Vis Sci. 1983;24:1143–6.

    PubMed  CAS  Google Scholar 

  58. Ciulla TA, Criswell MH, Danis RP, Hill TE. Intravitreal triamcinolone acetonide inhibits choroidal neovascularization in a laser-treated rat model. Arch Ophthalmol. 2001;119:399–404.

    PubMed  CAS  Google Scholar 

  59. Danis RP, Bingaman DP, Yang Y, Ladd B. Inhibition of preretinal and optic nerve head neovascularization in pigs by intravitreal triamcinolone acetonide. Ophthalmology. 1996;103:2099–104.

    PubMed  CAS  Google Scholar 

  60. Antoszyk AN, Gottlieb JL, Machemer R, Hatchell DL. The effects of intravitreal triamcinolone acetonide on experimental preretinal neovascularization. Graefes Arch Clin Exp Ophthalmol. 1993;231:34–40.

    Article  PubMed  CAS  Google Scholar 

  61. Wilson CA, Berkowitz BA, Sato Y, Ando N, Handa JT, de Juan Jr E. Treatment with intravitreal steroid reduces blood-retinal barrier breakdown due to retinal photocoagulation. Arch Ophthalmol. 1992;110:1155–9.

    PubMed  CAS  Google Scholar 

  62. Gillies MC, Simpson JM, Luo W, et al. A randomized clinical trial of a single dose of intravitreal triamcinolone acetonide for neovascular age-related macular degeneration: one-year results. Arch Ophthalmol. 2003;121:667–73.

    Article  PubMed  CAS  Google Scholar 

  63. Gillies MC, Simpson JM, Billson FA, et al. Safety of an intravitreal injection of triamcinolone: results from a randomized clinical trial. Arch Ophthalmol. 2004;122:336–40.

    Article  PubMed  CAS  Google Scholar 

  64. Bakri SJ, Beer PM. The effect of intravitreal triamcinolone acetonide on intraocular pressure. Ophthalmic Surg Lasers Imaging. 2003;34:386–90.

    PubMed  Google Scholar 

  65. Moshfeghi DM, Kaiser PK, Scott IU, et al. Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol. 2003;136:791–6.

    Article  PubMed  CAS  Google Scholar 

  66. Nelson ML, Tennant MT, Sivalingam A, Regillo CD, Belmont JB, Martidis A. Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection. Retina. 2003;23:686–91.

    Article  PubMed  Google Scholar 

  67. Schmidt-Erfurth U, Hasan T. Mechanisms of action of photodynamic therapy with verteporfin for the treatment of age-related macular degeneration. Surv Ophthalmol. 2000;45:195–214.

    Article  PubMed  CAS  Google Scholar 

  68. Schmidt-Erfurth U, Hasan T, Schomacker K, Flotte T, Birngruber R. In vivo uptake of liposomal benzoporphyrin derivative and photothrombosis in experimental corneal neovascularization. Lasers Surg Med. 1995;17:178–88.

    Article  PubMed  CAS  Google Scholar 

  69. Schmidt-Erfurth U, Hasan T, Gragoudas E, Michaud N, Flotte TJ, Birngruber R. Vascular targeting in photodynamic occlusion of subretinal vessels. Ophthalmology. 1994;101:1953–61.

    PubMed  CAS  Google Scholar 

  70. Schlotzer-Schrehardt U, Viestenz A, Naumann GO, Laqua H, Michels S, Schmidt-Erfurth U. Dose-related structural effects of photodynamic therapy on choroidal and retinal structures of human eyes. Graefes Arch Clin Exp Ophthalmol. 2002;240:748–57.

    Article  PubMed  CAS  Google Scholar 

  71. Debefve E, Pegaz B, van den Bergh H, et al. Video monitoring of neovessel occlusion induced by photodynamic therapy with verteporfin (Visudyne), in the CAM model. Angiogenesis. 2008;11(3):235–43. Epub 2008 Mar 7.

    Google Scholar 

  72. Verteporfin Roundtable Participants. Guidelines for using verteporfin (Visudyne) in photodynamic therapy for choroidal neovascularization due to age-related macular degeneration and other causes: update. Retina. 2005;25:119–34.

    Article  Google Scholar 

  73. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. 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. 2001;119:198–207.

    Google Scholar 

  74. Verteporfin in Photodynamic Therapy (VIP) Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization – verteporfin in photodynamic therapy report 2. Am J Ophthalmol. 2001;131:541–60.

    Article  Google Scholar 

  75. Visudyne in Minimally Classic CNV (VIM) Study Group. Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial. Arch Ophthalmol. 2005;123:448–57.

    Article  Google Scholar 

  76. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) and Verteporfin in Photodynamic Therapy (VIP) Study Groups. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: meta-analysis of 2-year safety results in three randomized clinical trials: treatment of age-related macular degeneration with photodynamic therapy and verteporfin in photodynamic therapy study report no. 4. Retina. 2004;24:1–12.

    Article  Google Scholar 

  77. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) and Verteporfin in Photodynamic Therapy (VIP) Study Groups. Acute severe visual acuity decrease after photodynamic therapy with verteporfin: case reports from randomized clinical trials – TAP and VIP Report No. 3. Am J Ophthalmol. 2004;137:683–96. Curr Med Res Opin.

    Article  CAS  Google Scholar 

  78. Kaiser PK, Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: 5-year results of two randomized clinical trials with an open-label extension – TAP Report No. 8. Graefes Arch Clin Exp Ophthalmol. 2006;244:1132–42.

    Article  PubMed  CAS  Google Scholar 

  79. Michels S, Schmidt-Erfurth U, Rosenfeld PJ. Promising new treatments for neovascular age-related macular degeneration. Expert Opin Investig Drugs. 2006;15:779–93.

    Article  PubMed  CAS  Google Scholar 

  80. Adamis AP, Shima DT. The role of vascular endothelial growth factor in ocular health and disease. Retina. 2005;25:111–8.

    Article  PubMed  Google Scholar 

  81. Gragoudas ES, Adamis AP, Cunningham Jr ET, et al. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med. 2004;351:2805–16.

    Article  PubMed  CAS  Google Scholar 

  82. Ruckman J, Green LS, Beeson J, et al. 2’-Fluoropyrimidine RNA-based aptamers to the 165-amino acid form of vascular endothelial growth factor (VEGF165). Inhibition of receptor binding and VEGF-induced vascular permeability through interactions requiring the exon 7-encoded domain. J Biol Chem. 1998;273:20556–67.

    Article  PubMed  CAS  Google Scholar 

  83. Chakravarthy U, Adamis AP, Cunningham Jr ET, et al. Year 2 efficacy results of 2 randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration. Ophthalmology. 2006;113:1508–25.

    PubMed  Google Scholar 

  84. Gaudreault J, Fei D, Rusit J, et al. Preclinical pharmacokinetics of Ranibizumab (rhuFabV2) after a single intravitreal administration. Invest Ophthalmol Vis Sci. 2005;46:726–33.

    Article  PubMed  Google Scholar 

  85. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419–31.

    Article  PubMed  CAS  Google Scholar 

  86. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432–44.

    Article  PubMed  CAS  Google Scholar 

  87. Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration: a phase I/II multicenter, controlled, multidose study. Ophthalmology. 2006;113(4):642.e1–4.

    Article  Google Scholar 

  88. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.

    Article  PubMed  CAS  Google Scholar 

  89. Waisbourd M, Loewenstein A, Goldstein M, Leibovitch I. Targeting vascular endothelial growth factor: a promising strategy for treating age-related macular degeneration. Drugs Aging. 2007;24:643–62.

    Article  PubMed  CAS  Google Scholar 

  90. Avery RL, Pieramici DJ, Rabena MD, et al. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology. 2006;113:363–72.

    Article  PubMed  Google Scholar 

  91. Bashshur ZF, Bazarbachi A, Schakal A, et al. Intravitreal bevacizumab for the management of choroidal neovascularization in age-related macular degeneration. Am J Ophthalmol. 2006;142:1–9.

    Article  PubMed  CAS  Google Scholar 

  92. Costa RA, Jorge R, Calucci D, et al. Intravitreal bevacizumab for choroidal neovascularization caused by AMD (IBeNA Study): results of a phase I dose-escalation study. Invest Ophthalmol Vis Sci. 2006;47:4569–78.

    Article  PubMed  Google Scholar 

  93. Spaide RF, Laud K, Fine HF, et al. Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina. 2006;26:383–90.

    Article  PubMed  Google Scholar 

  94. Rich RM, Rosenfeld PJ, Puliafito CA, et al. Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Retina. 2006;26:495–511.

    Article  PubMed  Google Scholar 

  95. Manzano RP, Peyman GA, Khan P, Kivilcim M. Testing intravitreal toxicity of bevacizumab (Avastin). Retina. 2006;26:257–61.

    Article  PubMed  Google Scholar 

  96. Slakter JS, Bochow TW, D’Amico DJ, et al. Anecortave acetate (15 milligrams) versus photodynamic therapy for treatment of subfoveal neovascularization in age-related macular degeneration. Ophthalmology. 2006;113:3–13.

    Article  PubMed  Google Scholar 

  97. Clark AF. AL-3789: a novel ophthalmic angiostatic steroid. Expert Opin Investig Drugs. 1997;6:1867–77.

    Article  PubMed  CAS  Google Scholar 

  98. Kwak N, Okamoto N, Wood JM, Campochiaro PA. VEGF is major stimulator in model of choroidal neovascularization. Invest Ophthalmol Vis Sci. 2000;41:3158–64.

    PubMed  CAS  Google Scholar 

  99. Shen J, Samul R, Silva RL, et al. Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1. Gene Ther. 2006;13:225–34.

    Article  PubMed  CAS  Google Scholar 

  100. Ciulla TA, Criswell MH, Danis RP, et al. Squalamine lactate reduces choroidal neovascularization in a laser-injury model in the rat. Retina. 2003;23:808–14.

    Article  PubMed  Google Scholar 

  101. Campochiaro PA, Dong NQ, Mahmood SS, 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. 2006;17:177–9.

    Article  Google Scholar 

  102. Rosenfeld PJ, Rich RM, Lalwani GA. Ranibizumab: phase III clinical trial results. Ophthalmol Clin North Am. 2006;19:361–72.

    PubMed  Google Scholar 

  103. Regillo CD, Brown DM, Abraham P, et al. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study Year 1. Am J Ophthalmol. 2008;145:239–48.

    Article  PubMed  CAS  Google Scholar 

  104. Bergers G, Song S, Meyer-Morse N, et al. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003;111:1287–95.

    PubMed  CAS  Google Scholar 

  105. Bradley J, Ju M, Robinson GS. Combination therapy for the treatment of ocular neovascularization. Angiogenesis. 2007;10:141–8.

    Article  PubMed  CAS  Google Scholar 

  106. 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. 2006;168:2036–53.

    Article  PubMed  CAS  Google Scholar 

  107. Azab M, Boyer DS, Bressler NM, et al. Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial. Arch Ophthalmol. 2005;123:448e57.

    Google Scholar 

  108. Schmidt-Erfurth U, Schlotzer-Schrehard U, Cursiefen C, et al. Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2003;44:4473e80.

    Article  Google Scholar 

  109. Kaiser PK. Combination therapy with verteporfin and anti-VEGF agents in neovascular age-related macular degeneration: where do we stand? Br J Ophthalmol. 2010;94(2):143–5.

    Article  PubMed  Google Scholar 

  110. Shah GK, Sang DN, Hughes MS. Verteporfin combination regimens in the treatment of neovascular AMD. Retina. 2009;29(2):133–48.

    Article  PubMed  Google Scholar 

  111. Alon T, Hemo I, Itin A, Pe’er J, Stone J, Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med. 1995;1:1024–8.

    Article  PubMed  CAS  Google Scholar 

  112. Emerson MV, Lauer AK. Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema. BioDrugs. 2007;21:245–57.

    Article  PubMed  CAS  Google Scholar 

  113. Nishijima K, Ng YS, Zhong L, 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. Am J Pathol. 2007;171:53–67.

    Article  PubMed  CAS  Google Scholar 

  114. Schlingemann RO. Role of growth factors and the wound healing response in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2004;242:91–101.

    Article  PubMed  CAS  Google Scholar 

  115. Rogers AH, Martidis A, Greenberg PB, Puliafito CA. OCT findings following PDT of CNV. Am J Ophthalmol. 2002;240:748–57.

    Google Scholar 

  116. Schmidt-Erfurth U, Laqua H, Schlotzer-Schrehard U, et al. Histopathological changes following photodynamic therapy in human eyes. Arch Ophthalmol. 2002;120:835–44.

    PubMed  Google Scholar 

  117. Spaide RF, Sorenson J, Maranan L. Combined photodynamic therapy with verteporfin and intravitreal triamcinolone acetonide for choroidal neovascularization. Ophthalmology. 2003;110:1517–25.

    Article  PubMed  Google Scholar 

  118. Spaide RF, Sorenson J, Maranan L. Photodynamic therapy with verteporfin combined with intravitreal injection of triamcinolone acetonide for ­choroidal neovascularization. Ophthalmology. 2005;112:301–4.

    Article  PubMed  Google Scholar 

  119. Rechtman E, Danis RP, Pratt LM, Harris A. Intravitreal triamcinolone with photodynamic therapy for subfoveal choroidal neovascularisation in age related macular degeneration. Br J Ophthalmol. 2004;88:344–7.

    Article  PubMed  CAS  Google Scholar 

  120. Moshfeghi A, Puliafito C, Rosenfeld P. Combination verteporfin therapy and intravitreal triamcinolone n neovascular age-related macular degeneration. Presented at the 2004 Meeting of the Retina Society, Baltimore, 30 Sept–3 Oct 2004.

    Google Scholar 

  121. Roth DB, Walsman S, Modi A, et al. Intravitreal triamcinolone combined with photodynamic therapy for exudative macular degeneration. Presented at the American Academy of Ophthalmology and European Society of Ophthalmology 2004 Joint Meeting; New Orleans, 23–26 Oct 2004.

    Google Scholar 

  122. Augustin AJ, Schmidt-Erfurth U. PDT and triamcinolone for the treatment of occult CNV in AMD. Presented at the 27th Annual Macula Society Meeting, Las Vegas, 26 Feb–1 Mar 2004.

    Google Scholar 

  123. El Matri L, Baklouti K, Mghaieth F, et al. Photodynamic therapy and intravitreal triamcinolone for exudative [sic] age related macular degeneration. Invest Ophthalmol Vis Sci. 2004;45:EAbstract 3162.

    Google Scholar 

  124. Bhavsar AR. Combined verteporfin therapy and intravitreal triamcinolone in the treatment of minimally classic subfoveal CNV with or without RAP lesions. Presented at the American Academy of Ophthalmology and European Society of Ophthalmology 2004 Joint Meeting, New Orleans, 23–26 Oct 2004.

    Google Scholar 

  125. Spaide RF, Sorenson J, Maranan L. Combined photodynamic therapy with verteporfin and intravitreal triamcinolone for juxtafoveal and extrafoveal choroidal neovascularization. Presented at the American Academy of Ophthalmology and European Society of Ophthalmology 2004 Joint Meeting, New Orleans, 23–26 Oct 2004.

    Google Scholar 

  126. Johnson RN, Yang S, McDonald HR, Ai E, Jumper JM. Combined photodynamic therapy and intravitreal triamcinolone acetonide for AMD. Presented at the American Academy of Ophthalmology and European Society of Ophthalmology 2004 Joint Meeting, New Orleans, 23–26 Oct 2004.

    Google Scholar 

  127. Augustin AJ, Schmidt-Erfurth U. Verteporfin therapy combined with intravitreal triamcinolone in all types of CNV due to AMD. Ophthalmology. 2006;113(1):14–22.

    Article  PubMed  Google Scholar 

  128. Chan WM, Lai TY, Wong AL, Tong JP, Liu DT, Lam DS. Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of subfoveal choroidal neovascularisation in age related macular degeneration: a comparative study. Br J Ophthalmol. 2006;90:337–41.

    Article  PubMed  Google Scholar 

  129. Ergun E, Maar N, Ansari-Shahrezaei S, Wimpissinger B, Krepler K, Wedrich A, et al. Photodynamic therapy with verteporfin and intravitreal triamcinolone acetonide in the treatment of neovascular age-related macular degeneration. Am J Ophthalmol. 2006;142:10–6.

    Article  PubMed  CAS  Google Scholar 

  130. Arias L, Garcia-Arumi J, Ramon JM, Badia M, Rubio M, Pujol O. Photodynamic therapy with intravitreal triamcinolone in predominantly classic choroidal neovascularization: one-year results of a randomized study. Ophthalmology. 2006;113:2243–50.

    Article  PubMed  Google Scholar 

  131. Ruiz-Moreno JM, Montero JA, Barile S, Zarbin MA. Photodynamic therapy and high-dose intravitreal triamcinolone to treat exudative age-related macular degeneration: 2-year outcome. Retina. 2007;27:458–61.

    Article  PubMed  Google Scholar 

  132. Maberley D et al. Photodynamic therapy and intravitreal triamcinolone for neovascular age-related macular degeneration a randomized clinical trial. Ophthalmology. 2009;116(11):2149–57.

    Article  PubMed  Google Scholar 

  133. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials — TAP report 1. Arch Ophthalmol. 1999;117:1329–45.

    Google Scholar 

  134. Eyetech Pharma. Division of Anti-inflammatory, Analgesic and Ophthalmic Drug Products Advisory Committee Meeting Briefing Package for Macugen 2004. Available at http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-053B1_02_FDABackgrounder.pdf. Accessed January 23, 2010.

  135. Antoszyk AN et al. Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration (FOCUS): year 2 results. Am J Ophthalmol. 2008;145(5):862–74.

    Article  PubMed  CAS  Google Scholar 

  136. Lazic R, Gabric N. Veteporfin therapy and intravitreal bevacizumab combined and alone in CNV due to AMD. Ophthalmology. 2007;114(6):1179–85.

    Article  PubMed  Google Scholar 

  137. Kaiser PK et al. Verteporfin photodynamic therapy combined with intravitreal bevacizumab for neovascular age-related macular degeneration. Ophthalmology. 2009;116:747–55.

    Article  PubMed  Google Scholar 

  138. QLT Annouces 12-Month Results From Novartis Sponsored MONT BLANC Study. Available at http://www.qltinc.com/newsCenter/2009/090615.htm. Accessed June 9, 2011

  139. Augustin AJ, Puls S, Offermann I. Triple therapy for CNV due to AMD. Retina. 2007;27(2):133–40.

    Article  PubMed  Google Scholar 

  140. Yip PP, Woo CF, Tang HHY, Ho CK. Triple therapy for neovascular AMD using single-session PDT combined with intravitreal bevacizumab and triamcinolone. Br J Ophthalmol. 2009;93(6):754–8.

    Article  PubMed  CAS  Google Scholar 

  141. Ehmann D, García R. Triple therapy for neovascular age-related macular degeneration (verteporfin photodynamic therapy, intravitreal dexamethasone, and intravitreal bevacizumab). Can J Ophthalmol. 2010;45(1):36–40.

    Article  PubMed  Google Scholar 

  142. Bakri SJ, Couch SM, McCannel CA, Edwards AO. Same-day triple therapy with photodynamic therapy, intravitreal dexamethasone, and bevacizumab in wet age-related macular degeneration. Retina. 2009;29(5):573–8.

    Article  PubMed  Google Scholar 

  143. Ahmadieh H et al. Single-session photodynamic therapy combined with intravitreal bevacizumab and triamcinolone for neovascular AMD. BMC Ophthalmol. 2007;7:10.

    Article  PubMed  CAS  Google Scholar 

  144. Reduced Fluence Visudyne-Anti-VEGF-Dexamethasone In Combination for AMD Lesions (RADICAL). Available at http://www.clinicaltrials.gov/ct2/show/NCT00492284. Accessed June 9, 2011.

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Authors and Affiliations

  1. Cole Eye Institute, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH, 44195, USA

    Nathan Steinle M.D.

  2. Cole Eye Institution, Cleveland Clinic, Cleveland, OH, USA

    Peter K. Kaiser M.D.

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  1. Nathan Steinle M.D.
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Correspondence to Nathan Steinle M.D. .

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  1. Wills Eye Hospital, Walnut St. 840, Philadelphia, 19107, Pennsylvania, USA

    Allen C. Ho

  2. Wills Eye Hospital, Walnut St. 840, Philadelphia, 19107, Pennsylvania, USA

    Carl D. Regillo

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Steinle, N., Kaiser, P.K. (2011). Combination Therapy with Ocular Photodynamic Therapy for Age-Related Macular Degeneration. In: Ho, A., Regillo, C. (eds) Age-related Macular Degeneration Diagnosis and Treatment. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0125-4_7

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