VEGF-targeted therapy and beyond: Pharmacotherapy and emerging treatments in agerelated macular degeneration

Expert Review of Clinical Pharmacology

Volumn 3, Issue 2, 2010, Pages 243-252

  McGimpsey, Stuart J ^a   Chakravarthy, Usha ^b  

^a ROYAL VICTORIA HOSPITAL   (United Kingdom)

^b QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

Author keywords

Integrin; Macular degeneration; Neovascular age related macular degeneration; PDGF; Ranibizumab; SiRNA; VEGF Trap; Wet age related macular degeneration

Indexed keywords

AFLIBERCEPT; AGN 21175; AL 39324; ANTIOXIDANT; ATG 3; BEVACIZUMAB; BEVASIRANIB; EVEROLIMUS; GLATIRAMER; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INTEGRIN; MAMMALIAN TARGET OF RAPAMYCIN; NICOTINIC RECEPTOR BLOCKING AGENT; PAZOPANIB; PEGAPTANIB; PF 4523655; PLACEBO; PLATELET DERIVED GROWTH FACTOR; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; RANIBIZUMAB; RAPAMYCIN; RTP 801I 14; SIRNA 027; SMALL INTERFERING RNA; TG 100801; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN; VASCULOTROPIN A; VATALANIB; VISUAL PIGMENT; VOLOCIXIMAB;

ANGIOGENESIS; ANTIOXIDANT ACTIVITY; CLINICAL FEATURE; DOWNSTREAM PROCESSING; DRUG COST; DRUG TARGETING; EYE INFECTION; HISTOPATHOLOGY; HUMAN; IMMUNOMODULATION; MOLECULAR MECHANICS; NONHUMAN; OXIDATIVE STRESS; PHOTODYNAMIC THERAPY; PHOTORECEPTOR CELL; PROTEIN SYNTHESIS INHIBITION; RETINA INJURY; RETINA MACULA AGE RELATED DEGENERATION; RETINA NEOVASCULARIZATION; REVIEW; SIGNAL TRANSDUCTION; SURGICAL INSTRUMENT; TELETHERAPY; VISUAL ACUITY;

EID: 77949385563     PISSN: 17512433     EISSN: None     Source Type: Journal    
DOI: 10.1586/ecp.10.6     Document Type: Review

References (47)

1. Roth F, Bindewald A, Holz FG. Key pathophysiologic pathways in age-related macular disease. Graefes Arch. Clin. Exp. Ophthalmol. 242(8), 710-716 (2004)
2. Macular Photocoagulation Study Group. Occult choroidal neovascularization. Infuence on visual outcome in patients with age-related macular degeneration. Arch. Ophthalmol. 114, 400-412 (1996).
3. Yannuzzi LA, Freund KB, Takahashi BS. Review of retinal angiomatous proliferation or type 3 neovascularization. Retina 28(3), 375-384 (2008).
4. Ciardella AP, Donsoff IM, Huang SJ, Costa DL, Yannuzzi LA. Polypoidal choroidal vasculopathy. Surv. Ophthalmol. 49(1), 25-37 (2004).
5. Yuda K, Inoue Y, Tomidokoro A, Tamaki Y, Yanagi Y. Nerve fber layer thickness in exudative age-related macular degeneration in Japanese patients. Graefes Arch. Clin. Exp. Ophthalmol. 248(3), 353-359 (2010).
6. Song SJ, Youm DJ, Chang Y, Yu HG. Age-related macular degeneration in a screened South Korean population: prevalence, risk factors, and subtypes. Ophthalmic Epidemiol. 16(5), 304-310 (2009).
7. Grossniklaus HE, Green WR. Choroidal neovascularization. Am. J. Ophthalmol. 137(3), 496-503 (2004).
8. Grant MB, May WS, Caballero S et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat. Med. 6, 607-612 (2002).
9. Hattori K, Heissing B, Wu Y et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1-stem cells from bone marrow microenvironment. Nat. Med. 8, 841-849 (2002).
10. Loane E, Kelliher C, Beatty S, Nolan JM. The rationale and evidence base for a protective role of macular pigment in age-related maculopathy. Br. J. Ophthalmol. 92(9), 1163-1168 (2008)
11. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, b-carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch. Ophthalmol. 119(10), 1417-1436 (2001).
12. Nozaki M, Raisler BJ, Sakurai E et al. Drusen complement components C3a and C5a promote choroidal neovascularization. Proc. Natl Acad. Sci. USA 103(7), 2328-2333 (2006).
13. Haines JL, Hauser MA, Schmidt S et al. Complement factor H variant increases the risk of age-related macular degeneration. Science 308(5720), 419-421 (2005).
14. Rakic JM, Lambert V, Devy L et al. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 44, 3186-3193 (2003).
15. Usui T, Ishida S, Yamashiro K et al. VEGF164(165) as the pathological isoform: differential leukocyte and endothelial responses through VEGFR1 and VEGFR2. Invest. Ophthalmol. Vis. Sci. 45, 368-374 (2004).
16. Nowak JZ. Age-related macular degeneration (AMD): pathogenesis and therapy. Pharmacol. Rep. 58, 353-363 (2006).
17. Macular Photocoagulation Study (MPS) Group. Argon laser photocoagulation for senile macular degeneration. Results of a randomized clinical trial. Arch. Ophthalmol. 100, 912-918 (1982)
18. Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) study group. Photodynamic therapy of subfoveal choroidal neovascularization in age related macular degeneration with verteporfn: one-year results of 2 randomized clinical trials-TAP report. Arch. Ophthalmol. 117, 1329-1345 (1999).
19. Bressler NM. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfn: two-year results of 2 randomized clinical trials-TAP Report no. 2. Arch. Ophthalmol. 119, 198-207 (2001).
20. Gragoudas ES, Adamis AP, Cunningham ET Jr et al. Pegaptanib for neovascular age-related macular degeneration. N. Engl. J. Med. 351, 2805-2816 (2004).
21. Rosenfeld PJ, Brown DM, Heier JS et al. Ranibizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 355, 1419-1431 (2006).
22. Brown DM, Kaiser PK, Michels M et al.; for the Anchor Study Group. Comparison of ranibizumab and verteporfn photodynamic therapy for neovascular age-related macular degeneration. N. Engl. J. Med. 355, 1432-1444 (2006).
23. Wong TY, Chakravarthy U, Klein R et al. The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-ana lysis. Ophthalmology 115(1), 116-126 (2008).
24. Csaky K, Do DV. Safety implications of vascular endothelial growth factor blockade for subjects receiving intravitreal anti-vascular endothelial growth factor therapies. Am. J. Ophthalmol. 148(5), 647-656 (2009).
25. Eldem B. Visual acuity response profles for patients with choroidal neovascular AMD treated with quarterly dosing of ranibizumab in the EXCITE study. Presented at: The Retina Congress. Sheraton New York, NY, USA, 30 September-4 October (2009).
26. 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. 145(2), 239-248 (2008).
27. Nguyen QD, Shah SM, Browning DJ et al. A Phase 1 study of intravitreal vascular endothelial growth factor trap-eye in patients with neovascular age-related macular degeneration. Ophthalmolog y 116, 2141-2148 (2009).
28. Schmidt Erfurth U. Verteporfn photodynamic therapy and ranibizumab combination for subfoveal CNV secondary to AMD. 12 month effcacy. results of the Mont Blanc Study. Presented at: The Retina Congress. Sheraton New York, NY, USA, 30 September-4 October (2009).
29. Avila MP, Farah ME, Santos A et al. Twelve month safety and visual acuity results from a feasibility study of intraocular EPI retinal radiation therapy for the treatment of subfoveal CNV secondary to AMD. Retina 29, 157-169 (2009).
30. Retina subspecialty day 'breaking news' symposium. Presented at: A AO 2009. San Francisco, CA, USA, 15-16 October (2009).
31. Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat. Rev. Mol. Cell. Biol. 10, 307-318 (2009).
32. Shoshani T, Faerman A, Mett I et al. Identifcation of a novel hypoxia-inducible factor 1-responsive gene, RTP801, involved in apoptosis. Mol. Cell. Biol. 22, 2283-2293 (2002).
33. Kim I, Ryan AM, Rohan R et al. Constitutive expression of VEGF, VEGFR-1, and VEGFR-2 in normal eyes. Invest. Ophthalmol. Vis. Sci. 40, 2115-2121 (1999).
34. Luo BH, Carman CV, Springer TA. Structural basis of integrin regulation and signaling. Annu. Rev. Immunol. 25, 619-647 (2007).
35. Avraamides CJ, Garmy-Susini B, Varner JA. Integrins in angiogenesis and lymphangiogenesis. Nat. Rev. Cancer 8, 604-617 (2008).
36. 1 integrin. J. Cell. Sci. 116, 3479-3489 (2003).
37. Hellstrom M, Gerhardt H, Kalen K et al. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J. Cell Biol. 153, 543-553 (2001).
38. Benjamin LE, Hemo I, Keshet E. A plasticity window for blood vessel remodeling is defned by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 125, 1591-1598 (1998).
39. Jo N, Mailhos C, Ju M, Inhibition of platelet-derived growth factor B signaling enhances the effcacy of anti-vascular endothelial growth factor therapy in multiple models of ocular neovascularization. Am. J. Pathol. 168, 2036-2053, (2006).
40. Takahashi K, Saishin Y, Saishin Y, et al. Suppression and regression of choroidal neovascularization by the multitargeted kinase inhibitor pazopanib. Arch. Ophthalmol. 127, 494-499 (2009).
41. Kleinman ME, Yamada K, Takeda A et al. Sequence-and target-independent angiogenesis suppression by siRNA via TLR3. Nature 452(7187), 591-597 (2009).
42. Chakravarthy U, Beatty S, Stevenson M; the CARMA Study Group. Functional and morphological outcomes in the CARMA clinical trial. Invest. Ophthalmol. Vis. Sci. 50 (2009) (E-Abstract 1257).
43. Radu RA, Han Y, Bui TV et al. Reductions in serum vitamin A arrest accumulation of toxic retinal fuorophores: a potential therapy for treatment of lipofuscin-based retinal diseases. IOVS 46, 4393-4401 (2005).
44. Wu J, DiPietrantonio A, Hsieh T. Mechanism of fenretinide (4-HPR)-induced cell death. Apoptosis 6(5), 377-388 (2001).
45. Arnon R, Aharoni R. Neuroprotection and neurogeneration in MS and its animal model EAE effected by glatiramer acetate. J. Neural Transm. 116(11), 1443-1449 (2009).
46. Achiron A, Feldman A, Gurevich M. Molecular profling of glatiramer acetate early treatment effects in multiple sclerosis. Dis. Markers 27(2), 63-73 (2009).
47. Landa G, Butovsky O, Shoshani J, Swchwartz M, Pollack A. Weekly vaccination with Copaxone (glatiramer acetate) as a potential therapy for dry age-related macular degeneration. Curr. Eye Res. 33, 1011-1013 (2008).