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Predictors of Visual Response to Intravitreal Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration

DOI: 10.1155/2013/676049

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Abstract:

Purpose. To identify the predictors of visual response to the bevacizumab treatment of neovascular age-related macular degeneration (AMD). Design. A cohort study within the Neovascular AMD Treatment Trial Using Bevacizumab (NATTB). Methods. This was a multicenter trial including 144 participants from the NATTB study. Visual outcomes measured by change in visual acuity (VA) score, proportion gaining ≥15 letters, and change in central retinal thickness (CRT) were compared among groups according to the baseline, demographic, and ocular characteristics and genotypes. Results. Mean change in the VA score was 9.2 ± 2.3 SD letters with a total of 46 participants (31.9%) gaining ≥15 letters. Change in median CRT was ?81.5?μm. Younger age, lower baseline VA score, shorter duration of neovascular AMD, and TT genotype in rs10490924 were significantly associated with greater VA score improvement ( , , , and , resp.). Lower baseline VA score and TT genotype in rs10490924 were significantly associated with a higher likelihood of gaining ≥15 letters ( , and , resp.). Conclusions. Baseline VA and genotype of rs10490924 were both important predictors for visual response to bevacizumab at 6 months. This trial is registered with the Registration no. NCT01306591. 1. Introduction Age-related macular degeneration (AMD) is the leading cause of blindness in people of 50 years of age or older in the developed countries [1, 2] and 80%–90% of severe vision loss and/or legal blindness can be attributed to neovascular AMD [3]. Vascular endothelial growth factor (VEGF) has been proven to play a major role in the pathogenesis of choroidal neovascularization (CNV) [4–7]. Bevacizumab (Avastin, Genentech), a monoclonal antibody to VEGF used intravenously as an anticancer agent, has been increasingly used “off-label” as an intravitreal therapy for neovascular AMD. Bevacizumab is derived from the same antibody as ranibizumab (Lucentis, Genentech) which is a smaller antigen-binding fragment and a frequently used anti-VEGF drug in the treatment of AMD [8–10]. Several studies show that bevacizumab has longer half-life in the vitreous fluid than ranibizumab because it is a full-length monoclonal antibody [11, 12], so the use of bevacizumab may reduce the frequency of visit and treatment for patients. Besides, a single dose of ranibizumab costs 40 times more than the cost of a single dose of bevacizumab [13]; this cost difference would undoubtedly have a notable influence on the patients who are treated for neovascular AMD in China. Since 2005, there have been short- and long-term

References

[1]  N. Congdon, B. O'Colmain, C. C. Klaver et al., “Causes and prevalence of visual impairment among adults in the United States,” Archives of Ophthalmology, vol. 122, no. 4, pp. 477–485, 2004.
[2]  D. Pascolini, S. P. Mariotti, G. P. Pokharel et al., “2002 Global update of available data on visual impairment: a compilation of population-based prevalence studies,” Ophthalmic Epidemiology, vol. 11, no. 2, pp. 67–115, 2004.
[3]  F. L. Ferris III, S. L. Fine, and L. Hyman, “Age-related macular degeneration and blindness due to neovascular maculopathy,” Archives of Ophthalmology, vol. 102, no. 11, pp. 1640–1642, 1984.
[4]  J. A. Wells, R. Murthy, R. Chibber et al., “Levels of vascular endothelial growth factor are elevated in the vitreous of patients with subretinal neovascularisation,” British Journal of Ophthalmology, vol. 80, no. 4, pp. 363–366, 1996.
[5]  F. Wang, K. G. Rendahl, W. C. Manning, D. Quiroz, M. Coyne, and S. S. Miller, “AAV-mediated expression of vascular endothelial growth factor induces choroidal neovascularization in rat,” Investigative Ophthalmology and Visual Science, vol. 44, no. 2, pp. 781–790, 2003.
[6]  R. Hera, M. Keramidas, M. Peoc'h, M. Mouillon, J.-P. Romanet, and J.-J. Feige, “Expression of VEGF and angiopoietins in subfoveal membranes from patients with age-related macular degeneration,” American Journal of Ophthalmology, vol. 139, no. 4, pp. 589–596, 2005.
[7]  K. Spilsbury, K. L. Garrett, W.-Y. Shen, I. J. Constable, and P. E. Rakoczy, “Overexpression of vascular endothelial growth factor (VEGF) in the retinal pigment epithelium leads to the development of choroidal neovascularization,” American Journal of Pathology, vol. 157, no. 1, pp. 135–144, 2000.
[8]  D. M. Brown, M. Michels, P. K. Kaiser, J. S. Heier, J. P. Sy, and T. Ianchulev, “Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study,” Ophthalmology, vol. 116, no. 1, pp. 57–65, 2009.
[9]  P. Abraham, H. Yue, and L. Wilson, “Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 2,” American Journal of Ophthalmology, vol. 150, no. 3, pp. 315–e1, 2010.
[10]  U. Schmidt-Erfurth, B. Eldem, R. Guymer et al., “Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study,” Ophthalmology, vol. 118, no. 5, pp. 831–839, 2011.
[11]  J. Gaudreault, D. Fei, J. Rusit, P. Suboc, and V. Shiu, “Preclinical pharmacokinetics of ranibizumab (rhuFabV2) after a single intravitreal administration,” Investigative Ophthalmology and Visual Science, vol. 46, no. 2, pp. 726–733, 2005.
[12]  S. J. Bakri, M. R. Snyder, J. M. Reid, J. S. Pulido, M. K. Ezzat, and R. J. Singh, “Pharmacokinetics of intravitreal ranibizumab (Lucentis),” Ophthalmology, vol. 114, no. 12, pp. 2179–2182, 2007.
[13]  D. F. Martin, M. G. Maguire, G.-S. Ying, J. E. Grunwald, S. L. Fine, and G. J. Jaffe, “Ranibizumab and bevacizumab for neovascular age-related macular degeneration,” The New England Journal of Medicine, vol. 364, no. 20, pp. 1897–1908, 2011.
[14]  R. L. Avery, D. J. Pieramici, M. D. Rabena, A. A. Castellarin, M. A. Nasir, and M. J. Giust, “Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration,” Ophthalmology, vol. 113, no. 3, pp. 363–372, 2006.
[15]  S. Aisenbrey, F. Ziemssen, M. V?lker et al., “Intravitreal bevacizumab (Avastin) for occult choroidal neovascularization in age-related macular degeneration,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 245, no. 7, pp. 941–948, 2007.
[16]  Z. F. Bashshur, Z. A. Haddad, A. Schakal, R. F. Jaafar, M. Saab, and B. N. Noureddin, “Intravitreal bevacizumab for treatment of neovascular age-related macular degeneration: a one-year prospective study,” American Journal of Ophthalmology, vol. 145, no. 2, pp. 249–e2, 2008.
[17]  Z. F. Bashshur, Z. A. Haddad, A. R. Schakal, R. F. Jaafar, A. Saad, and B. N. Noureddin, “Intravitreal bevacizumab for treatment of neovascular age-related macular degeneration: the second year of a prospective study,” American Journal of Ophthalmology, vol. 148, no. 1, pp. 59–65, 2009.
[18]  X. Li, Y. Hu, X. Sun, J. Zhang, and M. Zhang, “Bevacizumab for neovascular age-related macular degeneration in China,” Ophthalmology, vol. 119, no. 10, pp. 2087–2093, 2012.
[19]  D. S. Boyer, A. N. Antoszyk, C. C. Awh, R. B. Bhisitkul, H. Shapiro, and N. R. Acharya, “Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration,” Ophthalmology, vol. 114, no. 2, pp. 246–252, 2007.
[20]  P. K. Kaiser, D. M. Brown, K. Zhang et al., “Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results,” American Journal of Ophthalmology, vol. 144, no. 6, pp. 850–857, 2007.
[21]  G. S. Ying, J. Huang, M. G. Maguire et al., “Baseline predictors for one-year visual outcomes with ranibizumab or bevacizumab for neovascular age-related macular degeneration,” Ophthalmology, vol. 120, no. 1, pp. 122–129, 2013.
[22]  M. A. Brantley Jr., A. M. Fang, J. M. King, A. Tewari, S. M. Kymes, and A. Shiels, “Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to intravitreal bevacizumab,” Ophthalmology, vol. 114, no. 12, pp. 2168–2173, 2007.
[23]  D. Imai, K. Mori, K. Horie-Inoue et al., “CFH, VEGF, and PEDF genotypes and the response to intravitreous injection of bevacizumab for the treatment of age-related macular degeneration,” Journal of Ocular Biology, Diseases, and Informatics, vol. 3, no. 2, pp. 53–59, 2010.
[24]  J. Tian, X. Qin, K. Fang et al., “Association of genetic polymorphisms with response to bevacizumab for neovascular age-related macular degeneration in the Chinese population,” Pharmacogenomics, vol. 13, no. 7, pp. 779–787, 2012.
[25]  W. Smith, J. Assink, R. Klein et al., “Risk factors for age-related macular degeneration: pooled findings from three continents,” Ophthalmology, vol. 108, no. 4, pp. 697–704, 2001.
[26]  T. E. Clemons, R. C. Milton, R. Klein, J. M. Seddon, and F. L. Ferris III, “Risk factors for the incidence of advanced age-related macular degeneration in the Age-Related Eye Disease Study (AREDS): AREDS report no. 19,” Ophthalmology, vol. 112, no. 4, pp. 533–539, 2005.
[27]  J. C. Khan, D. A. Thurlby, H. Shahid et al., “Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation,” British Journal of Ophthalmology, vol. 90, no. 1, pp. 75–80, 2006.
[28]  S. J. Teper, A. Nowinska, J. Pilat, A. Palucha, and E. Wylegala, “Involvement of genetic factors in the response to a variable-dosing ranibizumab treatment regimen for age-related macular degeneration,” Molecular Vision, vol. 16, pp. 2598–2604, 2010.
[29]  A. Orlin, D. Hadley, W. Chang et al., “Association between high-risk disease loci and response to anti-vascular endothelial growth factor treatment for wet age-related macular degeneration,” Retina, vol. 32, no. 1, pp. 4–9, 2012.
[30]  K. Yamashiro, K. Tomita, A. Tsujikawa et al., “Factors associated with the response of age-related macular degeneration to intravitreal ranibizumab treatment,” American Journal of Ophthalmology, vol. 154, no. 1, pp. 125–136, 2012.
[31]  B. Kloeckener-Gruissem, D. Barthelmes, S. Labs et al., “Genetic association with response to intravitreal ranibizumab in patients with neovascular AMD,” Investigative ophthalmology & Visual Science, vol. 52, no. 7, pp. 4694–4702, 2011.
[32]  M. McKibbin, M. Ali, S. Bansal et al., “CFH, VEGF and HTRA1 promoter genotype may influence the response to intravitreal ranibizumab therapy for neovascular age-related macular degeneration,” British Journal of Ophthalmology, vol. 96, no. 2, pp. 208–212, 2012.
[33]  B. S. Conklin, W. Zhao, D.-S. Zhong, and C. Chen, “Nicotine and cotinine up-regulate vascular endothelial growth factor expression in endothelial cells,” American Journal of Pathology, vol. 160, no. 2, pp. 413–418, 2002.
[34]  M. Pons and M. E. Marin-Casta?o, “Nicotine increases the VEGF/PEDF ratio in retinal pigment epithelium: a possible mechanism for CNV in passive smokers with AMD,” Investigative Ophthalmology & Visual Science, vol. 52, no. 6, pp. 3842–3853, 2011.
[35]  M. Fujihara, N. Nagai, T. E. Sussan, S. Biswal, and J. T. Handa, “Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice,” PLoS One, vol. 3, no. 9, Article ID e3119, 2008.
[36]  K. M. Bertram, C. J. Baglole, R. P. Phipps, and R. T. Libby, “Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: implications for age-related macular degeneration,” American Journal of Physiology. Cell Physiology, vol. 297, no. 5, pp. C1200–C1210, 2009.
[37]  M. Pons and M. E. Marin-Casta?o, “Cigarette smoke-related hydroquinone dysregulates MCP-1, VEGF and PEDF expression in retinal pigment epithelium in vitro and in vivo,” PLoS One, vol. 6, no. 2, Article ID e16722, 2011.
[38]  A. Takeuchi, M. Takeuchi, K. Oikawa et al., “Effects of dioxin on vascular endothelial growth factor (VEGF) production in the retina associated with choroidal neovascularization,” Investigative Ophthalmology and Visual Science, vol. 50, no. 7, pp. 3410–3416, 2009.
[39]  Y. Solberg, M. Rosner, and M. Belkin, “The association betwen cigarette smoking and ocular diseases,” Survey of Ophthalmology, vol. 42, no. 6, pp. 535–547, 1998.
[40]  G. Lutty, J. Grunwald, A. B. Majji, M. Uyama, and S. Yoneya, “Changes in choriocapillaris and retinal pigment epithelium in age-related macular degeneration,” Molecular Vision, vol. 5, no. article 35, 1999.
[41]  B. R. Hammond Jr., B. R. Wooten, and D. M. Snodderly, “Cigarette smoking and retinal carotenoids: implications for age-related macular degeneration,” Vision Research, vol. 36, no. 18, pp. 3003–3009, 1996.
[42]  B. R. Hammond Jr. and M. Caruso-Avery, “Macular pigment optical density in a southwestern sample,” Investigative Ophthalmology and Visual Science, vol. 41, no. 6, pp. 1492–1497, 2000.

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