SHORT-TERM SAFETY AND EFFICACY OF INTRAVITREAL BEVACIZUMAB (AVASTIN) FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION

Purpose: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech Inc.) for the treatment of neovascular age-related macular degeneration (ARMD). Methods: A retrospective review was performed on consented patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All patients received intravitreal bevacizumab at baseline with additional monthly injections given at the discretion of the treating physician. At each visit, a routine Snellen visual acuity assessment was performed followed by an ophthalmic examination and optical coherence tomography (OCT) imaging. Results: Fifty–three eyes of 50 patients received an intravitreal bevacizumab injection between May and August 2005. Including the month 3 visit, the average number of injections was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or systemic adverse events were identified. Improvements in visual acuity and central retinal thickness measurements were evident by week 1 and continued through month 3. At month 3, the mean visual acuity improved from 20/160 to 20/125 (P<0.001) and the mean central retinal thickness decreased by 99.6 &mgr;m (P<0.001). Conclusion: Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.

[1]  B. Keyt,et al.  Identification of Vascular Endothelial Growth Factor Determinants for Binding KDR and FLT-1 Receptors , 1996, The Journal of Biological Chemistry.

[2]  P. D. de Jong,et al.  Increased expression of angiogenic growth factors in age-related maculopathy , 1997, The British journal of ophthalmology.

[3]  P. Rosenfeld,et al.  Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) for neovascular age-related macular degeneration. , 2006, Ophthalmology.

[4]  Philip J Rosenfeld,et al.  Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration. , 2005, Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye.

[5]  Richard F Spaide,et al.  INTRAVITREAL BEVACIZUMAB TREATMENT OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION , 2006, Retina.

[6]  R. Cuthbertson,et al.  Intraocular pharmacokinetics and safety of a humanized monoclonal antibody in rabbits after intravitreal administration of a solution or a PLGA microsphere formulation. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[7]  J. Rakic,et al.  Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. , 2003, Investigative ophthalmology & visual science.

[8]  E S Gragoudas,et al.  Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. , 1996, Archives of ophthalmology.

[9]  P. Rosenfeld,et al.  Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration twelve-week results of an uncontrolled open-label clinical study. , 2005, Ophthalmology.

[10]  Dennis P. Han Intravitreal human immune globulin in a rabbit model of Staphylococcus aureus toxin-mediated endophthalmitis: a potential adjunct in the treatment of endophthalmitis. , 2004, Transactions of the American Ophthalmological Society.

[11]  Hung V. Nguyen,et al.  The Carboxyl-terminal Domain(111165) of Vascular Endothelial Growth Factor Is Critical for Its Mitogenic Potency (*) , 1996, The Journal of Biological Chemistry.

[12]  P. Rosenfeld,et al.  Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration: twenty-four-week results of an uncontrolled open-label clinical study. , 2006, Ophthalmology.

[13]  Napoleone Ferrara,et al.  Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. , 2005, Biochemical and biophysical research communications.

[14]  Napoleone Ferrara,et al.  Vascular endothelial growth factor: basic science and clinical progress. , 2004, Endocrine reviews.

[15]  A. D. de Vos,et al.  Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen. , 1999, Journal of molecular biology.

[16]  D. Eliott,et al.  Basic fibroblast growth factor and vascular endothelial growth factor are present in epiretinal and choroidal neovascular membranes. , 1996, American journal of ophthalmology.

[17]  R. Avery,et al.  Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. , 2006, Ophthalmology.

[18]  D. Hinton,et al.  Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes. , 1996, Investigative ophthalmology & visual science.

[19]  R. Cuthbertson,et al.  Comparisons of the Intraocular Tissue Distribution, Pharmacokinetics, and Safety of 125I-Labeled Full-Length and Fab Antibodies in Rhesus Monkeys Following Intravitreal Administration , 1999, Toxicologic pathology.

[20]  Y. Ogura,et al.  Vascular endothelial growth factor family and receptor expression in human choroidal neovascular membranes. , 2002, Microvascular research.

[21]  E. Gragoudas,et al.  Pegaptanib for neovascular age-related macular degeneration. , 2004, The New England journal of medicine.

[22]  Leonard,et al.  Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. , 1997, Cancer research.

[23]  Kenneth J. Hillan,et al.  Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer , 2004, Nature Reviews Drug Discovery.

[24]  D. Shima,et al.  THE ROLE OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN OCULAR HEALTH AND DISEASE , 2005, Retina.

[25]  S. Seregard,et al.  Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor. , 1996, Investigative ophthalmology & visual science.

[26]  M. Blumenkranz,et al.  Maximum tolerated dose of a humanized anti-vascular endothelial growth factor antibody fragment for treating neovascular age-related macular degeneration. , 2005, Ophthalmology.

[27]  Z. Tomić,et al.  [Photodynamic therapy of subfoveal choroidal neovascularization]. , 2007, Srpski arhiv za celokupno lekarstvo.

[28]  J. P. Sy,et al.  Ranibizumab for treatment of neovascular age-related macular degeneration: a phase I/II multicenter, controlled, multidose study. , 2006, Ophthalmology.