Predictors of visual response to intravitreal bevacizumab for treatment of neovascular age-related macular degeneration

Kai Fang, Jun Tian, Xueying Qing, Shuai Li, Jing Hou, Juan Li, Wenzhen Yu, Dafang Chen, Yonghua Hu, Xiaoxin Li, Kai Fang, Jun Tian, Xueying Qing, Shuai Li, Jing Hou, Juan Li, Wenzhen Yu, Dafang Chen, Yonghua Hu, Xiaoxin Li

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 μ m. Younger age, lower baseline VA score, shorter duration of neovascular AMD, and TT genotype in rs10490924 were significantly associated with greater VA score improvement (P = 0.028, P < 0.001, P = 0.02, and P = 0.039, resp.). Lower baseline VA score and TT genotype in rs10490924 were significantly associated with a higher likelihood of gaining ≥15 letters (P = 0.028, and P = 0.021, 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.

Figures

Figure 1
Figure 1
(a) Association of baseline visual acuity (VA) score with VA score change at 6 months. Baseline VA score was significantly associated with VA score change at 6 months (P = 0.015). *P = 0.036 (the first group was the reference). (b) Association of duration of neovascular age-related macular degeneration (AMD) with VA score change at 6 months. Duration of neovascular AMD was significantly associated with VA score change at 6 months (P = 0.005). *P = 0.005; †P = 0.007; ‡P = 0.001 (the first group was the reference).
Figure 2
Figure 2
(a) Association of baseline visual acuity (VA) score with proportion of ≥15 letters gaining from baseline at 6 months. Baseline VA score was significantly associated with proportion of ≥15 letters gaining from baseline at 6 months (P = 0.005). *P = 0.015 (the first group was the reference). (b) Association of duration of neovascular age-related macular degeneration (AMD) with proportion of ≥15 letters gaining from baseline at 6 months. Duration of neovascular AMD was significantly associated with proportion of ≥15 letters gaining from baseline at 6 months (P = 0.021). *P = 0.009 (the first group was the reference).

References

    1. Congdon N, O'Colmain B, Klaver CC, et al. Causes and prevalence of visual impairment among adults in the United States. Archives of Ophthalmology. 2004;122(4):477–485.
    1. Pascolini D, Mariotti SP, Pokharel GP, et al. 2002 Global update of available data on visual impairment: a compilation of population-based prevalence studies. Ophthalmic Epidemiology. 2004;11(2):67–115.
    1. Ferris FL, III, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Archives of Ophthalmology. 1984;102(11):1640–1642.
    1. Wells JA, Murthy R, Chibber R, et al. Levels of vascular endothelial growth factor are elevated in the vitreous of patients with subretinal neovascularisation. British Journal of Ophthalmology. 1996;80(4):363–366.
    1. Wang F, Rendahl KG, Manning WC, Quiroz D, Coyne M, Miller SS. AAV-mediated expression of vascular endothelial growth factor induces choroidal neovascularization in rat. Investigative Ophthalmology and Visual Science. 2003;44(2):781–790.
    1. Hera R, Keramidas M, Peoc’h M, Mouillon M, Romanet J-P, Feige J-J. Expression of VEGF and angiopoietins in subfoveal membranes from patients with age-related macular degeneration. American Journal of Ophthalmology. 2005;139(4):589–596.
    1. Spilsbury K, Garrett KL, Shen W-Y, Constable IJ, Rakoczy PE. Overexpression of vascular endothelial growth factor (VEGF) in the retinal pigment epithelium leads to the development of choroidal neovascularization. American Journal of Pathology. 2000;157(1):135–144.
    1. Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology. 2009;116(1):57–65.
    1. Abraham P, Yue H, Wilson L. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 2. American Journal of Ophthalmology. 2010;150(3):315–e1.
    1. Schmidt-Erfurth U, Eldem B, Guymer R, et al. Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study. Ophthalmology. 2011;118(5):831–839.
    1. Gaudreault J, Fei D, Rusit J, Suboc P, Shiu V. Preclinical pharmacokinetics of ranibizumab (rhuFabV2) after a single intravitreal administration. Investigative Ophthalmology and Visual Science. 2005;46(2):726–733.
    1. Bakri SJ, Snyder MR, Reid JM, Pulido JS, Ezzat MK, Singh RJ. Pharmacokinetics of intravitreal ranibizumab (Lucentis) Ophthalmology. 2007;114(12):2179–2182.
    1. Martin DF, Maguire MG, Ying G-S, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. The New England Journal of Medicine. 2011;364(20):1897–1908.
    1. Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology. 2006;113(3):363–372.
    1. Aisenbrey S, Ziemssen F, Völker M, et al. Intravitreal bevacizumab (Avastin) for occult choroidal neovascularization in age-related macular degeneration. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2007;245(7):941–948.
    1. Bashshur ZF, Haddad ZA, Schakal A, Jaafar RF, Saab M, Noureddin BN. Intravitreal bevacizumab for treatment of neovascular age-related macular degeneration: a one-year prospective study. American Journal of Ophthalmology. 2008;145(2):249–e2.
    1. Bashshur ZF, Haddad ZA, Schakal AR, Jaafar RF, Saad A, Noureddin BN. Intravitreal bevacizumab for treatment of neovascular age-related macular degeneration: the second year of a prospective study. American Journal of Ophthalmology. 2009;148(1):59–65.
    1. Li X, Hu Y, Sun X, Zhang J, Zhang M. Bevacizumab for neovascular age-related macular degeneration in China. Ophthalmology. 2012;119(10):2087–2093.
    1. Boyer DS, Antoszyk AN, Awh CC, Bhisitkul RB, Shapiro H, Acharya NR. Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology. 2007;114(2):246–252.
    1. Kaiser PK, Brown DM, Zhang K, et al. Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results. American Journal of Ophthalmology. 2007;144(6):850–857.
    1. Ying GS, Huang J, Maguire MG, et al. Baseline predictors for one-year visual outcomes with ranibizumab or bevacizumab for neovascular age-related macular degeneration. Ophthalmology. 2013;120(1):122–129.
    1. Brantley MA, Jr., Fang AM, King JM, Tewari A, Kymes SM, Shiels A. Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to intravitreal bevacizumab. Ophthalmology. 2007;114(12):2168–2173.
    1. Imai D, Mori K, Horie-Inoue K, 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. 2010;3(2):53–59.
    1. Tian J, Qin X, Fang K, et al. Association of genetic polymorphisms with response to bevacizumab for neovascular age-related macular degeneration in the Chinese population. Pharmacogenomics. 2012;13(7):779–787.
    1. Smith W, Assink J, Klein R, et al. Risk factors for age-related macular degeneration: pooled findings from three continents. Ophthalmology. 2001;108(4):697–704.
    1. Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL., 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. 2005;112(4):533–539.
    1. Khan JC, Thurlby DA, Shahid H, 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. 2006;90(1):75–80.
    1. Teper SJ, Nowinska A, Pilat J, Palucha A, Wylegala E. Involvement of genetic factors in the response to a variable-dosing ranibizumab treatment regimen for age-related macular degeneration. Molecular Vision. 2010;16:2598–2604.
    1. Orlin A, Hadley D, Chang W, et al. Association between high-risk disease loci and response to anti-vascular endothelial growth factor treatment for wet age-related macular degeneration. Retina. 2012;32(1):4–9.
    1. Yamashiro K, Tomita K, Tsujikawa A, et al. Factors associated with the response of age-related macular degeneration to intravitreal ranibizumab treatment. American Journal of Ophthalmology. 2012;154(1):125–136.
    1. Kloeckener-Gruissem B, Barthelmes D, Labs S, et al. Genetic association with response to intravitreal ranibizumab in patients with neovascular AMD. Investigative ophthalmology & Visual Science. 2011;52(7):4694–4702.
    1. McKibbin M, Ali M, Bansal S, 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. 2012;96(2):208–212.
    1. Conklin BS, Zhao W, Zhong D-S, Chen C. Nicotine and cotinine up-regulate vascular endothelial growth factor expression in endothelial cells. American Journal of Pathology. 2002;160(2):413–418.
    1. Pons M, Marin-Castaño ME. Nicotine increases the VEGF/PEDF ratio in retinal pigment epithelium: a possible mechanism for CNV in passive smokers with AMD. Investigative Ophthalmology & Visual Science. 2011;52(6):3842–3853.
    1. Fujihara M, Nagai N, Sussan TE, Biswal S, Handa JT. Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice. PLoS One. 2008;3(9)e3119
    1. Bertram KM, Baglole CJ, Phipps RP, Libby RT. 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. 2009;297(5):C1200–C1210.
    1. Pons M, Marin-Castaño ME. Cigarette smoke-related hydroquinone dysregulates MCP-1, VEGF and PEDF expression in retinal pigment epithelium in vitro and in vivo. PLoS One. 2011;6(2)e16722
    1. Takeuchi A, Takeuchi M, Oikawa K, et al. Effects of dioxin on vascular endothelial growth factor (VEGF) production in the retina associated with choroidal neovascularization. Investigative Ophthalmology and Visual Science. 2009;50(7):3410–3416.
    1. Solberg Y, Rosner M, Belkin M. The association betwen cigarette smoking and ocular diseases. Survey of Ophthalmology. 1998;42(6):535–547.
    1. Lutty G, Grunwald J, Majji AB, Uyama M, Yoneya S. Changes in choriocapillaris and retinal pigment epithelium in age-related macular degeneration. Molecular Vision. 1999;5(article 35)
    1. Hammond BR, Jr., Wooten BR, Snodderly DM. Cigarette smoking and retinal carotenoids: implications for age-related macular degeneration. Vision Research. 1996;36(18):3003–3009.
    1. Hammond BR, Jr., Caruso-Avery M. Macular pigment optical density in a southwestern sample. Investigative Ophthalmology and Visual Science. 2000;41(6):1492–1497.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe