Targeting vascular endothelial growth factor: a promising strategy for treating age-related macular degeneration.
Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the industrialised world. While treatment options for advanced AMD have been rather limited until recently, the introduction of intravitreal injections of anti-angiogenic agents appears to be a promising and revolutionary mode of treatment for this blinding disease. Vascular endothelial growth factor (VEGF) appears to play a pivotal role in the pathogenesis of choroidal neovascularisation, one of the cornerstones of advanced AMD. Pegaptanib, the first anti-VEGF treatment approved for AMD patients, is a VEGF-neutralising aptamer that specifically inhibits one isoform of VEGF (VEGF-165). Although evidence suggested that pegaptanib was superior to previous treatment options, results with this agent were still unsatisfactory. Ranibizumab is a humanised anti-VEGF monoclonal antibody fragment that inhibits all isotypes of VEGF. This new drug has demonstrated a high efficacy profile in terms of inhibiting disease progression and even improving visual acuity. Bevacizumab is a full-length anti-VEGF antibody that was originally approved for use in metastatic colon cancer and is under investigation as a low-cost off-label alternative for patients with AMD. There is growing evidence that this drug may be an effective and safe alternative to the more expensive ranibizumab, although prospective multicentre trials are required to fully investigate this issue. Undoubtedly, the concept of directly injecting anti-VEGF drugs into the vitreal cavity brings new hope to many AMD patients.
Waisbourd
Michael
M
Ophthalmology Department, Tel-Aviv Sourasky Medical Centre, Tel-Aviv University, Tel-Aviv, Israel. mwaisbourd@hotmail.com
Loewenstein
Anat
A
Goldstein
Michaella
M
Leibovitch
Igal
I
D000375:Aging; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000068258:Bevacizumab; D020256:Choroidal Neovascularization / Q000188:drug therapy; D016503:Drug Delivery Systems; D006801:Humans; D007267:Injections; D008268:Macular Degeneration / Q000188:drug therapy*; D000069579:Ranibizumab; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014792:Visual Acuity; D014822:Vitreous Body
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide; D042461:Vascular Endothelial Growth Factor A; C495058:pegaptanib; D000068258:Bevacizumab; D000069579:Ranibizumab
Retina. 2006 May-Jun;26(5):495-511
16770255
Retina. 2006 Mar;26(3):270-4
16508425
Br J Ophthalmol. 2006 Sep;90(9):1207-8
16929069
Br J Ophthalmol. 2006 Jul;90(7):922
16782958
Ophthalmology. 2006 Nov;113(11):2002.e1-12
17027972
Invest Ophthalmol Vis Sci. 2003 Jan;44(1):290-9
12506087
Br J Ophthalmol. 1997 Feb;81(2):154-62
9059252
Surv Ophthalmol. 2006 Jul-Aug;51(4):316-63
16818082
Ophthalmology. 2005 Jun;112(6):1035-47
15936441
Toxicol Pathol. 1999 Sep-Oct;27(5):536-44
10528633
N Engl J Med. 2006 Oct 5;355(14 ):1432-44
17021319
N Engl J Med. 2006 Oct 5;355(14):1409-12
17021315
Ophthalmology. 2006 Mar;113(3):501
16513466
Gene Ther. 2005 Oct;12 Suppl 1:S159-69
16231050
Am J Ophthalmol. 2006 Apr;141(4):752-4
16564819
N Engl J Med. 1971 Nov 18;285(21):1182-6
4938153
Retina. 2005 Dec;25(8):1065-84
16340538
Retina. 2006 Jul-Aug;26(6 Suppl):S17-20
16832293
Arch Ophthalmol. 2006 Nov;124(11):1532-42
17101999
Arch Ophthalmol. 2006 Oct;124(10 ):1478-9
17030717
Ophthalmology. 2006 Apr;113(4):633.e1-4
16483659
Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4569-78
17003454
Nat Rev Neurosci. 2006 Nov;7(11):860-72
17033682
JAMA. 2004 Apr 21;291(15):1900-1
15108691
Front Biosci. 1999 Feb 01;4:D141-52
9924144
Arch Ophthalmol. 2004 Apr;122(4):564-72
15078675
Clin Ther. 2006 Jan;28(1):36-44
16490578
Arch Ophthalmol. 2006 May;124(5):660-4
16682587
Ophthalmology. 2006 Apr;113(4):623.e1
16581423
Arch Ophthalmol. 2002 Mar;120(3):338-46
11879138
Exp Nephrol. 1998 Nov-Dec;6(6):480-7
9807017
Retina. 2006 Oct;26(8):859-70
17031284
N Engl J Med. 2004 Dec 30;351(27):2805-16
15625332
Br J Ophthalmol. 2006 Sep;90(9):1188-96
16929063
Retina. 2006 Mar;26(3):262-9
16508424
Ophthalmology. 2006 Sep;113(9):1508.e1-25
16828500
JAMA. 2005 Mar 23;293(12 ):1509-13
15784876
Invest Ophthalmol Vis Sci. 2006 Jan;47(1):357-63
16384985
Invest Ophthalmol Vis Sci. 2003 Jul;44(7):3186-93
12824270
N Engl J Med. 2006 Oct 5;355(14):1419-31
17021318
J Cell Sci. 2001 Mar;114(Pt 5):853-65
11181169
Retina. 2005 Oct-Nov;25(7):815-27
16205558
Arch Ophthalmol. 1991 Aug;109(8):1060-1
1867539
Pharmacol Rev. 2004 Dec;56(4):549-80
15602010
Am J Ophthalmol. 2006 Jul;142(1):1-9
16815245
Graefes Arch Clin Exp Ophthalmol. 2007 May;245(5):651-5
17006681
Invest Ophthalmol Vis Sci. 2005 Feb;46(2):726-33
15671306
Retina. 2006 Oct;26(8):871-6
17031285
Ophthalmology. 1992 Jun;99(6):933-43
1630784
Am J Ophthalmol. 2006 Jul;142(1):141-3
16815262
Ophthalmology. 2005 Apr;112(4):531-2
15808239
Acta Ophthalmol Scand. 2006 Oct;84(5):713-4
16965511
Adv Drug Deliv Rev. 2005 Dec 13;57(14):2063-79
16310884
N Engl J Med. 2006 Oct 5;355(14):1474-85
17021323
Curr Opin Mol Ther. 2003 Dec;5(6):673-9
14755895
Pharm Res. 2000 Dec;17(12):1503-10
11303960
Br J Ophthalmol. 2006 Nov;90(11):1344-9
16854824
Ophthalmol Clin North Am. 2006 Sep;19(3):361-72
16935211
Ophthalmology. 2005 Jun;112(6):1048-53
15885778
Retina. 2006 Apr;26(4):383-90
16603955
Microvasc Res. 2002 Jul;64(1):162-9
12074642
Ophthalmology. 2006 Mar;113(3):363-372.e5
16458968
Ophthalmic Surg Lasers Imaging. 2005 Jul-Aug;36(4):331-5
16156152
Retina. 2002 Apr;22(2):143-52
11927845
Arch Ophthalmol. 2001 Oct;119(10):1417-36
11594942
Retina. 2006 Oct;26(8):877-81
17031286
Arch Ophthalmol. 2005 Apr;123(4):509-16
15824225
Retina. 2006 Mar;26(3):257-61
16508423