Skip to main content
Log in

New Pharmacologic Approaches to Therapy for Age-Related Macular Degeneration

  • Novel Therapeutic Strategies
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

As a result of a better understanding of molecular mechanisms, a variety of new Pharmacologic treatments have recently been developed for patients with age-related macular degeneration (AMD). Efficacy and tolerability have been demonstrated for drugs targeting vascular endothelial growth factor (VEGF), a key player in the pathogenesis of choroidal neovascularization. Both pegaptanib (anti-VEGF aptamer) and ranibizumab (anti-VEGF antibody fragment), applied at 4- to 6-week intervals into the vitreous, modified the natural course of the disease in phase III clinical studies. Corticosteroids with anti-angiogenic properties also represent a treatment option for wet AMD. Both intravitreal triamcinolone and anecortave acetate, administered juxtasclerally, are currently being pursued.

The combination of different treatment strategies and potential synergistic effects offers new perspectives. While photodynamic therapy (PDT) combined with intravitreal triamcinolone is already frequently applied, other combinations (e.g. anti-VEGF drugs with PDT or antifibrotic agents) appear to be attractive alternatives. Pigment epithelium-derived factor represents another potential target, as well as inhibitors of matrix-metalloproteinases. With the advent of gene therapy, the use of small interfering RNA (siRNA) is also on the horizon.

Prophylactic measures are still limited. The combination of vitamins C and E, β-carotene, and zinc as used in the AREDS (Age-Related Eye Disease Study) reduces risk for conversion from early- to late-stage disease in patients with high-risk features, at least to some extent. Lutein and zeaxanthin dietary supplements for improvement of macular pigment density need to be investigated in future longitudinal trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Bird A. Age-related macular disease. Br J Ophthalmol 1996; 80(1): 2–3

    Article  PubMed  CAS  Google Scholar 

  2. Holz FG, Pauleikhoff D. Clinical manifestations. In: Holz FG, Pauleikhoff D, Spaide RF, et al., editors. Age-related macular degeneration. Berlin: Springer, 2004: 73–90

    Google Scholar 

  3. Beatty S, Koh H, Phil M, et al. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 2000; 45(2): 115–34

    Article  PubMed  CAS  Google Scholar 

  4. Spaide RF, Ho-Spaide WC, Browne RW, et al. Characterization of peroxidized lipids in Brach’s membrane. Retina 1999; 19(2): 141–7

    Article  PubMed  CAS  Google Scholar 

  5. Schmidt-Erfurth U. Nutrition and retina. Dev Ophthalmol 2005; 38: 120–47

    Article  PubMed  CAS  Google Scholar 

  6. Flamm P. Zur Therapie der degenerativen Makulopathie mit Cosaldon A + E. Klin Monatsbl Augenheilkd 1987; 190(1): 59–66

    Article  PubMed  CAS  Google Scholar 

  7. Karcioglu Z. Zinc in the eye. Surv Ophthalmol 1982; 27: 114–22

    Article  PubMed  CAS  Google Scholar 

  8. Newsome DA, Swartz M, Leone NC, et al. Oral zinc in macular degeneration. Arch Ophthalmol 1988; 106(2): 192–8

    Article  PubMed  CAS  Google Scholar 

  9. Kaminski MS, Yolton DP, Jordan WT, et al. Evaluation of dietary antioxidant levels and supplementation with ICAPS-Plus and Ocuvite. J Am Optom Assoc 1993; 64(12): 862–70

    PubMed  CAS  Google Scholar 

  10. Holz FG, Wolfensberger TJ, Piguet B, et al. Oral zinc-therapy in age-related macular degeneration: a double blind study. Ger J Ophthalmol 1993; 2 Suppl. 2: 391

    Google Scholar 

  11. The Eyetech Study Group. Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Ophthalmol 2003; 110: 979–86

    Article  Google Scholar 

  12. The AREDS Study Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001; 119(10): 1417–36

    Article  Google Scholar 

  13. Schutt F, Pauleikhoff D, Holz FG. Vitamine und Spurenelemente bei altersabhangiger Makuladegeneration. Aktuelle Empfehlungen, basierend auf den Resultaten der AREDS-Studie. Ophthalmologe 2002; 99: 301–3

    Article  PubMed  CAS  Google Scholar 

  14. Seigel D. AREDS investigators distort findings. Arch Ophthalmol 2002; 120(1): 100–1

    Article  PubMed  Google Scholar 

  15. De Luca LM, Ross SA. Beta-carotene increases lung cancer incidence in cigarette smokers. Nutr Rev 1996 Jun; 54(6): 178–80

    Google Scholar 

  16. Augustin AJ, Schmidt-Erfurth U. Critical comments on the ARED study [in German]. Ophthalmologe 2002; 99(4): 299–300

    Article  PubMed  CAS  Google Scholar 

  17. Pauleikhoff D, vanKuijk FJ, Bird AC. Makuläres pigment und altersabhängige makuladegeneration. Ophthalmologe 2001; 98: 511–9

    Article  PubMed  CAS  Google Scholar 

  18. Hammond B, Caruso-Avery M. Macular pigment optical density in a Southwestern sample. Invest Ophthalmol Vis Sci 2000; 41(6): 1492–7

    PubMed  Google Scholar 

  19. Beatty S, Murray IJ, Henson DB, et al. Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci 2001; 42(2): 439–46

    PubMed  CAS  Google Scholar 

  20. Hammond Jr BR, Johnson EJ, Russell RM, et al. Dietary modification of human macular pigment density. Invest Ophthalmol Vis Sci 1997; 38(9): 1795–801

    PubMed  Google Scholar 

  21. Berendschot TT, Goldbohm RA, Klopping WA, et al. Influence of lutein supplementation on macular pigment, assessed with two objective techniques. Invest Ophthalmol Vis Sci 2000; 41(11): 3322–6

    PubMed  CAS  Google Scholar 

  22. Landrum JT, Bone RA, Joa H, et al. A one year study of the macular pigment: the effect of 140 days of a lutein supplement. Exp Eye Res 1997; 65(1): 57–62

    Article  PubMed  CAS  Google Scholar 

  23. Bone RA, Landram JT, Guerra LH, et al. Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans. J Nutr 2003; 133(4): 992–8

    PubMed  CAS  Google Scholar 

  24. Falsini B, Piccardi M, Iarossi G, et al. Influence of short-term antioxidant supple-mentation on macular function in age-related maculopathy: a pilot study including electrophysiologic assessment. Ophthalmology 2003; 110(1): 51–60

    Article  PubMed  Google Scholar 

  25. Ey C. Future clinical trials: AREDS II with lutein/zeaxanthin [E-abstract 1228]. Ophthalmol Vis Sci 2005; 46 Suppl.

  26. Majji AB, Hayashi A, Kim HC, et al. Inhibition of choriocapillaris regeneration with genistein. Invest Ophthalmol Vis Sci 1999; 40(7): 1477–86

    PubMed  CAS  Google Scholar 

  27. Nakajima M, Cooney MJ, Tu AH, et al. Normalization of retinal vascular permeability in experimental diabetes with genistein. Invest Ophthalmol Vis Sci 2001; 42(9): 2110–4

    PubMed  CAS  Google Scholar 

  28. Gruber BL, Marchese MJ, Kew R. Angiogenic factors stimulate mast-cell migration. Blood 1995; 86(7): 2488–93

    PubMed  CAS  Google Scholar 

  29. Fotsis T, Pepper M, Adlercreutz H, et al. Genistein, a dietary ingested isoflavonoid, inhibits cell proliferation and in vitro angiogenesis. J Nutr 1995; 125(3 Suppl.): 790–7

    Google Scholar 

  30. Uyama M, Takahashi K, Ida N, et al. The second eye of Japanese patients with unilateral exudative age related macular degeneration. Br J Ophthalmol 2000 Sep; 84(9): 1018–23

    Article  PubMed  CAS  Google Scholar 

  31. Chang TS, Hay D, Courtright P. Age-related macular degeneration in Chinese-Canadians. Can J Ophthalmol 1999 Aug; 34(5): 266–71

    PubMed  CAS  Google Scholar 

  32. Wilson HL, Schwartz DM, Bhatt HR, et al. Statin and aspirin therapy are associated with decreased rates of choroidal neovascularization among patients with age-related macular degeneration. Am J Ophthalmol 2004; 137(4): 615–24

    PubMed  CAS  Google Scholar 

  33. Blanco-Colio LM, Tunon J, Martin-Ventura JL, et al. Anti-inflammatory and immunomodulatory effects of statins. Kidney Int 2003; 63(1): 12–23

    Article  PubMed  CAS  Google Scholar 

  34. Veillard N, Mach F. Statins: the new aspirin? Cell Mol Life Sci 2002; 51: 1771–86

    Article  Google Scholar 

  35. The Eye Disease Case-Control Study Group. Risk factors for neovascular age-related macular degeneration. Arch Ophthalmol 1992; 110(12): 1701–8

    Article  Google Scholar 

  36. Curcio CA, Presley JB, Malek G, et al. Esterified and unesterified cholesterol in drusen and basal deposits of eyes with age-related maculopathy. Exp Eye Res 2005 Dec; 81(6): 731–41

    Article  PubMed  CAS  Google Scholar 

  37. Malek G, Li CM, Guidry C, et al. Apolipoprotein B in cholesterol-containing drusen and basal deposits of human eyes with age-related maculopathy. Am J Pathol 2003 Feb; 162(2): 413–25

    Article  PubMed  CAS  Google Scholar 

  38. Curcio CA, Millican CL, Bailey T, et al. Accumulation of cholesterol with age in human Brach’s membrane. Invest Ophthalmol Vis Sci 2001 Jan; 42(1): 265–74

    PubMed  CAS  Google Scholar 

  39. Curcio CA, Millican CL, Bailey T, et al. Accumulation of cholesterol with age in human Bruch’s membrane. Invest Ophthalmol Vis Sci 2001; 42(1): 265–74

    PubMed  CAS  Google Scholar 

  40. Hall NF, Gale CR, Syddall H, et al. Risk of macular degeneration in users of statins: cross sectional study. BMJ 2001; 323: 375–6

    Article  PubMed  CAS  Google Scholar 

  41. Yang R, McCollum G, Bingaman D, et al. Inhibition of VEGF-induced endothelial cell proliferation and differentiation by steroidal and non-steroidal COX inhibitors with variable COX-l/COX-2 selectivity [E-abstract 1914]. Invest Ophthalmol Vis Sci 2004; 45 Suppl.

  42. Csaky KG. Phase II trial of Celebrex in photodynamic therapy (C-PDT) for neovascular age-related macular degeneration (AMD): rationale and baseline characteristics [E-abstract 1186]. Invest Ophthalmol Vis Sci 2004; 45 Suppl.

  43. Lutty G, Grunwald J, Majji AB, et al. Changes in choriocapillaris and retinal pigment epithelium in age-related macular degeneration. Mol Vis 1999; 5: 35

    PubMed  CAS  Google Scholar 

  44. Christen WG, Glynn RJ, Ajani UA, et al. Age-related maculopathy in a randomized trial of low-dose aspirin among US physicians. Arch Ophthalmol 2001; 119(8): 1143–9

    PubMed  CAS  Google Scholar 

  45. Goldberg J, Flowerdew G, Smith E, et al. Factors associated with age-related macular degeneration: an analysis of data from the first National Health and Nutrition Examination Survey. Am J Epidemiol 1988; 128(4): 700–10

    PubMed  CAS  Google Scholar 

  46. Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res 2003; 110(5-6): 255–8

    Article  PubMed  CAS  Google Scholar 

  47. Harris A, Ciulla TA, Pratt LM, et al. The effects of dorzolamide on choroidal and retinal perfusion in non-exudative age related macular degeneration. Br J Ophthalmol 2003; 87(6): 753–7

    Article  PubMed  CAS  Google Scholar 

  48. Pauleikhoff D, Chen JC, Chisholm IH, et al. Choroidal perfusion abnormality with age-related Bruch’s membrane change. Am J Ophthalmol 1990; 109(2): 211–7

    PubMed  CAS  Google Scholar 

  49. Folkman J. Tumor angiogenesis. Adv Cancer Res 1974; 19: 331–58

    Article  PubMed  CAS  Google Scholar 

  50. Miller J, Shima DT, Tolentino M, et al. Inhibition of VEGF prevents ocular neovascularization in a monkey model [abstract]. Invest Ophthalmol Vis Sci 1995; 36: 401

    Google Scholar 

  51. Spilsbury K, Garrett KL, Shen WY, et al. Overexpression of vascular endothelial growth factor (VEGF) in the retinal pigment epithelium leads to the development of choroidal neovascularization. Am J Pathol 2000; 157(1): 135–44

    Article  PubMed  CAS  Google Scholar 

  52. Hruby K. Aussichten und Grenzen der Behandlung seniler Makulopathien mit Phosphatiden. Wien Klin Wochenschr 1977; 89(13): 439–42

    PubMed  CAS  Google Scholar 

  53. Garrett K, Shen WY, Rakoczy PE. In vivo use of oligonucleotides to inhibit choroidal neovascularization in the eye. J Gene Med 2001; 3: 373–83

    Article  PubMed  CAS  Google Scholar 

  54. Gragoudas ES, Adamis AP, Cunningham Jr ET, et al. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004; 351(27): 2805–16

    Article  PubMed  CAS  Google Scholar 

  55. D’Amico D, Bird AC. VEGF Inhibition Study in Ocular Neovascularization-1 (VISION-1): safety evaluation from the pivotal Macugen™ (pegaptanib sodium) clinical trials [E-abstract 2363]. Invest Ophthalmol Vis Sci 2004; 45 Suppl.

  56. Pfizer Inc. Treatment results with MACUGEN® (pegaptanib sodium injection). MACUGEN [online]. Available from URL: http://www.macugen.com/treat-mentasp[Accessed 2006 Apr 28]

  57. 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(3): 338–46

    Article  PubMed  CAS  Google Scholar 

  58. 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. Epub 2006 Feb 13

  59. Heier JS. Review of Lucentis™ (randibizumab, rhuFab V2) phase I/II trial results: 6-month treatment of exsudative AMD [E-abstract 1109]. Invest Ophthalmol Vis Sci 2004; 45 Suppl.

  60. Novartis. New data from two leading clinical studies show Lucentis® is first therapy to improve vision in patients with wet age-related macular degeneration (AMD) [press release]. Novartis, 2005 Jul 18 [online]. Available from URL: http://dominoext.novartis.com/NC/NCPRREOl.nsf[Accessed 2006 Apr 28]

  61. Novartis. Preliminary data from second pivotal phase III study showed Lucentis® maintained or improved vision in 95 percent of patients with age-related macular degeneration (AMD) [press release]. Novartis, 2005 Nov 7 [online]. Available from URL: http://dominoext.novartis.com/NC/NCPRRE01.nsf[Accessed 2006 Apr 28]

  62. Ferrara N, Hillan KJ, Novotny W. Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun 2005 Jul 29; 333(2): 328–35

    Article  PubMed  CAS  Google Scholar 

  63. Michels S, Rosenfeld PJ, Puliafito CA, et al. Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration twelve-week results of an uncontrolled open-label clinical study. Ophthalmology 2005; 112(6): 1035–47

    Article  PubMed  Google Scholar 

  64. Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging 2005; 36(4): 331–5

    PubMed  Google Scholar 

  65. Rosenfeld PJ, Fung AE, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surg Lasers Imaging 2005 Jul–Aug; 36(4): 336–9

    PubMed  Google Scholar 

  66. Iturralde D, Spaide RF, Meyerle CB, et al. Intravitreal bevacizumab (Avastin) treatment of macular edema in central retinal vein occlusion: a short-term study. Retina 2006 Mar; 26(3): 279–84

    Article  PubMed  Google Scholar 

  67. Spaide RF, Fisher YL. Intravitreal bevacizumab (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage. Retina 2006 Mar; 26(3): 275–8

    Article  PubMed  Google Scholar 

  68. Avery RL, Pieramici DJ, Rabena MD, et al. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology 2006 Mar; 113(3): 363–72

    Article  PubMed  Google Scholar 

  69. Konner J, Dupont J. Use of soluble recombinant decoy receptor vascular endothelial growth factor trap (VEGF Trap) to inhibit vascular endothelial growth factor activity. Clin Colorectal Cancer 2004; 4 Suppl. 2: S81–5

    Article  Google Scholar 

  70. Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A 2002; 99(17): 11393–8

    Article  PubMed  CAS  Google Scholar 

  71. Saishin Y, Takahashi K, Lima e Silva R, et al. VEGF-Trap (R1R2) suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier. J Cell Physiol 2003; 195(2): 241–8

    Article  PubMed  CAS  Google Scholar 

  72. Ciulla TA, Criswell MH, Danis RP, et al. Squalamine lactate reduces choroidal neovascularization in a laser-injury model in the rat. Retina 2003; 23(6): 808–14

    Article  PubMed  Google Scholar 

  73. Genaidy M, Kazi AA, Peyman GA, et al. Effect of squalamine on iris neovascularization in monkeys. Retina 2002; 22(6): 772–8

    Article  PubMed  Google Scholar 

  74. Higgins RD, Sanders RJ, Yan Y, et al. Squalamine improves retinal neovascularization. Invest Ophthalmol Vis Sci 2000; 41(6): 1507–12

    PubMed  CAS  Google Scholar 

  75. Genaera. Genaera Corporation presents clinical results for EVIZON™ for treatment of age-related macular degeneration at the annual ASRS meeting [press release]. Genaera, 2005 Jul 18 [online]. Available from URL: http://www.genaera.com/pressreleases_toc.html[Accessed 2006 Apr 28]

  76. Stellmach V, Crawford SE, Zhou W, et al. Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor. Proc Natl Acad Sci U S A 2001; 98(5): 2593–7

    Article  PubMed  CAS  Google Scholar 

  77. Mori K, Gehlbach P, Ando A, et al. Regression of ocular neovascularization in response to increased expression of pigment epithelium-derived factor. Invest Ophthalmol Vis Sci 2002; 43(7): 2428–34

    PubMed  Google Scholar 

  78. Mori K, Gehlbach P, Yamamoto S, et al. AAV-mediated gene transfer of pigment epithelium-derived factor inhibits choroidal neovascularization. Invest Ophthalmol Vis Sci 2002; 43(6): 1994–2000

    PubMed  Google Scholar 

  79. Holekamp NM. Deficiency of anti-angiogenic pigment epithelial-derived factor in the vitreous of patients with wet age-related macular degeneration. In: Proceedings of the 34th Annual Scientific Meeting of the Retina Society; 2001 Sep 13–16; Chicago (IL). Boston (MA) The Retina Society, 2001: 66

  80. Renno RZ, Youssri AI, Michaud N, et al. Expression of pigment epithelium-derived factor in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 2002; 43(5): 1574–80

    PubMed  Google Scholar 

  81. Rasmussen H, Chu KW, Campochiaro P, et al. Clinical protocol. An open-label, phase I, single administration, dose-escalation study of ADGVPEDF.11 D (ADPEDF) in neovascular age-related macular degeneration (AMD). Hum Gene Ther2001; 12(16): 2029–32

    PubMed  CAS  Google Scholar 

  82. Harris A, Arend O, Arend S, et al. Effects of topical dorzolamide on retinal and retrobulbar hemodynamics. Acta Ophthalmol Scand 1996; 74(6): 569–72

    Article  PubMed  CAS  Google Scholar 

  83. Steen B, Sejersen S, Berglin L, et al. Matrix metalloproteinases and metal-loproteinase inhibitors in choroidal neovascular membranes. Invest Ophthalmol Vis Sci 1998; 39(11): 2194–200

    PubMed  CAS  Google Scholar 

  84. Shalinsky DR, Brekken J, Zou H, et al. Broad antitumor and antiangiogenic activities of AG3340, a potent and selective MMP inhibitor undergoing advanced oncology clinical trials. Ann N Y Acad Sci 1999; 878: 236–70

    Article  PubMed  CAS  Google Scholar 

  85. Holz FG, Miller DW. Pharmacological therapy for age-related macular degeneration: current developments and perspectives [in German]. Ophthalmologe 2003 Feb; 100(2): 97–103

    Article  PubMed  CAS  Google Scholar 

  86. Aeterna Zentaris. Neovastat® product sheet. Aeterna Zentaris [online]. Available from URL: http://www.aeternazentaris.com[Accessed 2006 Apr 28]

  87. Crum R, Szabo S, Folkman J. A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 1985; 230(4732): 1375–8

    Article  PubMed  CAS  Google Scholar 

  88. BenEzra D, Griffin BW, Maftzir G, et al. Topical formulations of novel angiostatic steroids inhibit rabbit corneal neovascularization. Invest Ophthalmol Vis Sci 1997; 38(10): 1954–62

    PubMed  CAS  Google Scholar 

  89. Penn JS, Rajaratnam VS, Collier RJ, et al. The effect of an angiostatic steroid on neovascularization in a rat model of retinopathy of prematurity. Invest Ophthalmol Vis Sci 2001; 42(1): 283–90

    PubMed  CAS  Google Scholar 

  90. Clark AF, Mellon J, Li XY, et al. Inhibition of intraocular tumor growth by topical application of the angiostatic steroid anecortave acetate. Invest Ophthalmol Vis Sci 1999; 40(9): 2158–62

    PubMed  CAS  Google Scholar 

  91. McNatt LG, Weimer L, Yanni J, et al. Angiostatic activity of steroids in the chick embryo CAM and rabbit cornea models of neovascularization. J Ocul Pharmacol Ther 1999; 15(5): 413–23

    Article  PubMed  CAS  Google Scholar 

  92. McNatt LG, Lane D, Clark AF. Angiostatic activity and metabolism of Cortisol in the chorioallantoic membrane (CAM) of the chick embryo. J Steroid Biochem Mol Biol 1992; 42(7): 687–93

    Article  PubMed  CAS  Google Scholar 

  93. Oikawa T, Hiragun A, Yoshida Y, et al. Angiogenic activity of rat mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene and its inhibition by medroxyprogesterone acetate: possible involvement of antiangiogenic action of medroxyprogesterone acetate in its tumor growth inhibition. Cancer Lett 1988; 43(1–2): 85–92

    Article  PubMed  CAS  Google Scholar 

  94. Proia AD, Hirakata A, McInnes JS, et al. The effect of angiostatic steroids and beta-cyclodextrin tetradecasulfate on corneal neovascularization in the rat. Exp Eye Res 1993; 57(6): 693–8

    Article  PubMed  CAS  Google Scholar 

  95. D’Amico DJ, Goldberg MF, Hudson H, Anecortave Acetate Clinical Study Group, et al. Anecortave acetate as monotherapy for the treatment of subfoveal lesions in patients with exudative age-related macular degeneration (AMD): interim (month 6) analysis of clinical safety and efficacy. Retina 2003 Feb; 23(1): 14–23

    Article  PubMed  Google Scholar 

  96. D’Amico DJ, Goldberg MF, Hudson H, Anecortave Acetate Clinical Study Group, et al. Anecortave acetate as monotherapy for treatment of subfoveal neovascularization in age-related macular degeneration: twelve-month clinical outcomes. Ophthalmology 2003 Dec; 110(12): 2372–83

    Article  PubMed  Google Scholar 

  97. Schmidt-Erfurth U, Michels S, Michels R, et al. Anecortave acetate for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Eur J Ophthalmol 2005; 15(4): 482–5

    PubMed  CAS  Google Scholar 

  98. Ciulla TA, Criswell MH, Danis RP, et al. Intravitreal triamcinolone acetonide inhibits choroidal neovascularization in a laser-treated rat model. Arch Ophthalmol 2001; 119(3): 399–404

    PubMed  CAS  Google Scholar 

  99. Spandau U, Sauder G, Jonas JB, et al. Angiostatic effect of crystalline triamcinolone acetonide on ocular neovascularization in vivo [E-abstract 2497]. Invest Ophthalmol Vis Sci 2002; 43 Suppl.

  100. Gillies M, Simpson J, 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(5): 667–73

    Article  PubMed  CAS  Google Scholar 

  101. Roth D, Spirn M, Yarian DL, et al. Intravitreal triamcinolone injection for the treatment of occult choroidal neovascularization associated with age-related macular degeneration [E-abstract 2500]. Invest Ophthalmol Vis Sci 2002; 43 Suppl.

  102. Moon S, Mieler WF, Holz ER. Pilot study of intravitreal injektion of triamcinolone acetonide in exsudative age-related macular degeneration [E-abstract 1220]. Invest Ophthalmol Vis Sci 2002; 43 Suppl.

  103. Jonas J, Kreissig I, Hugger P, et al. Intravitreal triamcinolone acetonide for exsudative age-related macular degeneration. Br J Ophthalmol 2003; 87: 462–8

    Article  PubMed  CAS  Google Scholar 

  104. Lambert V, Munaut C, Noel A, et al. Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization. FASEB J 2001; 15(6): 1021–7

    Article  PubMed  CAS  Google Scholar 

  105. Slakter JS, Bochow TW, D’Amico DJ, Anecortave Acetate Clinical Study Group, et al. Anecortave acetate (15 milligrams) versus photodynamic therapy for treatment of subfoveal neovascularization in age-related macular degeneration. Ophthalmology 2006 Jan; 113(1): 3–13

    Article  PubMed  Google Scholar 

  106. Spaide RF, Sorenson J, Maranan L. Combined photodynamic therapy with verte-porfin and intravitreal triamcinolone acetonide for choroidal neovascularization. Ophthalmology 2003; 110(8): 1517–25

    Article  PubMed  Google Scholar 

  107. 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(10): 4473–80

    Article  PubMed  Google Scholar 

  108. Rechtman E, Danis RP, Pratt LM, et al. Intravitreal triamcinolone with photodynamic therapy for subfoveal choroidal neovascularisation in age related macular degeneration. Br J Ophthalmol 2004; 88(3): 344–7

    Article  PubMed  CAS  Google Scholar 

  109. Spaide RF, Sorenson J, Maranan L. Photodynamic therapy with verteporfin combined with intravitreal injection of triamcinolone acetonide for choroidal neovascularization. Ophthalmology 2005; 112(2): 301–4

    Article  PubMed  Google Scholar 

  110. Gasparini G. Metronomic scheduling: the future of chemotherapy? Lancet Oncol 2001; 2: 733–40

    Article  PubMed  CAS  Google Scholar 

  111. Karl S, Bindewald A, Roth F, et al. Intravitreale methotrexat-injektionen bei choroidalen neovaskularisationen im rahmen der altersabhängigen makuladegeneration (AMD) [poster 158]. Proceedings of the German Society of Ophthalmology (DOG) 2004 Annual Meeting; 2004 Sep 23–26; Berlin

  112. Brouty-Boye D, Zetter BR. Inhibition of cell motility by interferon. Science 1980; 208(4443): 516–8

    Article  PubMed  CAS  Google Scholar 

  113. Engler CB, Sander B, Koefoed P, et al. Interferon alpha-2a treatment of patients with subfoveal neovascular macular degeneration: a pilot investigation. Acta Ophthalmol (Copenh) 1993; 71(1): 27–31

    Article  CAS  Google Scholar 

  114. Ezekowitz RA, Mulliken JB, Folkman J. Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med 1992; 326(22): 1456–63

    Article  PubMed  CAS  Google Scholar 

  115. Fung WE. Interferon alpha 2a for treatment of age-related macular degeneration. Am J Ophthalmol 1991; 112(3): 349–50

    PubMed  CAS  Google Scholar 

  116. Pharmacological Therapy for Macular Degeneration Study Group. Interferon alfa-2a is ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration: results of a prospective randomized placebo-controlled clinical trial. Pharmacological Therapy for Macular Degeneration Study Group. Arch Ophthalmol 1997; 115(7): 865–72

    Article  Google Scholar 

  117. Maguire M, Fine SL, Maguire AM, et al. AMDATS Research Group: results of the age-related macular degeneration and thalidomide study (AMDATS) [abstract]. Invest Ophthalmol Vis Sci 2001; 42: 233

    Google Scholar 

  118. Reich S, Fosnot J, Akiko K, et al. Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model. Mol Vis 2003; 9: 210–6

    PubMed  CAS  Google Scholar 

  119. Tolentino MJ, Brucker AJ, Joshua F, et al. Intravitreal injection of vascular endothelial growth factor small interfering RNA inhibits growth and leakage in a nonhuman primate, laser-induced model of choroidal Neovascularization. Retina 2004; 24: 132–8

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors received no funding to assist in the preparation of this article and have no conflicts of interest relevant to its contents.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nicole Eter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eter, N., Krohne, T.U. & Holz, F.G. New Pharmacologic Approaches to Therapy for Age-Related Macular Degeneration. BioDrugs 20, 167–179 (2006). https://doi.org/10.2165/00063030-200620030-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-200620030-00004

Keywords

Navigation