Journal Mobile Options
Table of Contents
Vol. 51, No. 1, 2014
Issue release date: December 2013
Ophthalmic Res 2014;51:1-8

VEGF Gene Polymorphism and Response to Intravitreal Ranibizumab in Neovascular Age-Related Macular Degeneration

dos Reis Veloso C.E. · Frota de Almeida L.N. · Recchia F.M. · Pelayes D. · Nehemy M.B.
aDepartment of Ophthalmology, Federal University of Minas Gerais, Belo Horizonte, Brazil; bVanderbilt Eye Institute, Nashville, Tenn., USA; cDepartment of Ophthalmology, Buenos Aires University, Buenos Aires, Argentina

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background/Aims: To investigate the association between VEGF gene polymorphism and response to ranibizumab in neovascular age-related macular degeneration (AMD). Methods: A total of 92 patients were genotyped for the VEGF rs1413711 single nucleotide polymorphism. Patients with neovascular AMD initially received 3 monthly ranibizumab intravitreal injections and were retreated as needed. Visual acuity (VA) and central retinal thickness (CRT) were measured before and 1, 3, 6 and 12 months after treatment. Results: For patients with TT and CT genotypes, paired comparisons of mean VA showed improvement when the data obtained at all visits were compared with baseline values, in contrast to patients with the CC genotype. CRT statistically improved at all visits for all genotypes. Conclusion: Patients with the CC genotype showed poorer long-term functional and anatomical response to anti-VEGF therapy. © 2013 S. Karger AG, Basel

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Veloso CE, Almeida LNF, de Marco LA, Vianna RNG, Nehemy MB: Importance of genetic polymorphisms in the response to age-related macular degeneration treatment. Rev Bras Oftalmol 2012;71:194-198.

    External Resources

  2. Congdon N, O'Colmain B, Klaver CC, Klein R, Muñoz B, Friedman DS, Kempen J, Taylor HR, Mitchell P, Eye Diseases Prevalence Research Group: Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 2004;122:477-485.
  3. Brown G, Brown MM: Let us wake the nation on the treatment for age-related macular degeneration. Curr Opin Ophthalmol 2010;21:169-171.
  4. Scholl HP, Fleckenstein M, Charbel Issa P, Keilhauer C, Holz FG, Weber BH: An update on the genetics of age-related macular degeneration. Mol Vis 2007;3:196-205.

    External Resources

  5. Klein R, Cruickshanks KJ, Nash SD, Krantz EM, Javier Nieto F, Huang GH, Pankow JS, Klein BE: The prevalence of age-related macular degeneration and associated risk factors. Arch Ophthalmol 2010;128:750-758.
  6. Priya RR, Chew EY, Swaroop A: Genetic studies of age-related macular degeneration: lessons, challenges, and opportunities for disease management. Ophthalmology 2012;119:2526-2536.
  7. Schaumberg DA, Hankinson SE, Guo Q, Rimm E, Hunter DJ: A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors. Arch Ophthalmol 2007;125:55-62.
  8. Shuler RK Jr, Hauser MA, Caldwell J, Gallins P, Schmidt S, Scott WK, Agarwal A, Haines JL, Pericak-Vance MA, Postel EA: Neovascular age-related macular degeneration and its association with LOC387715 and complement factor H polymorphism. Arch Ophthalmol 2007;125:63-67.
  9. Haines JL, Schnetz-Boutaud N, Schmidt S, Scott WK, Agarwal A, Postel EA, Olson L, Kenealy SJ, Hauser M, Gilbert JR, Pericak-Vance MA: Functional candidate genes in age-related macular degeneration: significant association with VEGF, VLDLR, and LRP6. Invest Ophthalmol Vis Sci 2006;47:329-335.
  10. Churchill AJ, Carter JG, Lovell HC, Ramsden C, Turner SJ, Yeung A, Escardo J, Atan D: VEGF polymorphisms are associated with neovascular age-related macular degeneration. Hum Mol Genet 2006;15:2955-2961.
  11. Janik-Papis K, Zaras M, Krzyzanowska A, Wozniak K, Blasiak J, Szaflik J, Szaflik JP: Association between vascular endothelial growth factor gene polymorphisms and age-related macular degeneration in a Polish population. Exp Mol Pathol 2009;87:234-238.
  12. Yu Y, Bhangale TR, Fagerness J, Ripke S, Thorleifsson G, Tan PL, Souied EH, Richardson AJ, Merriam JE, Buitendijk GH, Reynolds R, Raychaudhuri S, Chin KA, Sobrin L, Evangelou E, Lee PH, Lee AY, Leveziel N, Zack DJ, Campochiaro B, Campochiaro P, Smith RT, Barile GR, Guymer RH, Hogg R, Chakravarthy U, Robman LD, Gustafsson O, Sigurdsson H, Ortmann W, Behrens TW, Stefansson K, Uitterlinden AG, van Duijn CM, Vingerling JR, Klaver CC, Allikmets R, Brantley MA Jr, Baird PN, Katsanis N, Thorsteinsdottir U, Ioannidis JP, Daly MJ, Graham RR, Seddon JM: Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. Hum Mol Genet 2011;20:3699-3709.
  13. Lin JM, Wan L, Tsai YY, Lin HJ, Tsai Y, Lee CC, Tsai CH, Tseng SH, Tsai FJ: Vascular endothelial growth factor gene polymorphisms in age-related macular degeneration. Am J Ophthalmol 2008;145:1045-1051.
  14. Galan A, Ferlin A, Caretti L, Buson G, Sato G, Frigo AC, Foresta C: Association of age-related macular degeneration with polymorphisms in vascular endothelial growth factor and its receptor. Ophthalmology 2010;117:1769-1774.
  15. Almeida LN, Melilo-Carolino R, Veloso CE, Pereira PA, Miranda DM, de Marco LA, Nehemy MB: Homozygosity for the +674C>T polymorphism on VEGF gene is associated with age-related macular degeneration in a Brazilian cohort. Graefes Arch Clin Exp Ophthalmol 2012;250:185-189.
  16. Richardson AJ, Islam FM, Guymer RH, Cain M, Baird PN: A tag-single nucleotide polymorphisms approach to the vascular endothelial growth factor-A gene in age-related macular degeneration. Mol Vis 2007;13:2148-2152.

    External Resources

  17. Boekhoorn SS, Isaacs A, Uitterlinden AG, van Duijn CM, Hofman A, de Jong PT, Vingerling JR: Polymorphisms in the vascular endothelial growth factor gene and risk of age-related macular degeneration: the Rotterdam Study. Ophthalmology 2008;115:1899-1903.
  18. Fang AM, Lee AY, Kulkarni M, Osborn MP, Brantley MA Jr: Polymorphisms in the VEGFA and VEGFR-2 genes and neovascular age-related macular degeneration. Mol Vis 2009;15:2710-2719.

    External Resources

  19. Klein ML, Francis PJ, Rosner B, Reynolds R, Hamon SC, Schultz DW, Ott J, Seddon JM: CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration. Ophthalmology 2008;115:1019-1025.
  20. Goverdhan SV, Hannan S, Newsom RB, Luff AJ, Griffiths H, Lotery AJ: An analysis of the CFH Y402H genotype in AMD patients and controls from the UK, and response to PDT treatment. Eye (Lond) 2008;22:849-854.
  21. Brantley MA Jr, Edelstein SL, King JM, Plotzke MR, Apte RS, Kymes SM, Shiels A: Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to photodynamic therapy. Eye (Lond) 2009;23:626-631.
  22. Feng X, Xiao J, Longville B, Tan AX, Wu XN, Cooper MN, McAllister IL, Isaacs T, Palmer LJ, Constable IJ: Complement factor H Y402H and C-reactive protein polymorphism and photodynamic therapy response in age-related macular degeneration. Ophthalmology 2009;116:1908-1912.
  23. Seitsonen SP, Jarvela IE, Meri S, Tommila PV, Ranta PH, Immonen IJ: The effect of complement factor H Y402H polymorphism on the outcome of photodynamic therapy in age-related macular degeneration. Eur J Ophthalmol 2007;17:943-949.

    External Resources

  24. Chowers I, Meir T, Lederman M, Goldenberg-Cohen N, Cohen Y, Banin E, Averbukh E, Hemo I, Pollack A, Axer-Siegel R, Weinstein O, Hoh J, Zack DJ, Galbinur T: Sequence variants in HTRA1 and LOC387715/ARMS2 and phenotype and response to photodynamic therapy in neovascular age-related macular degeneration in populations from Israel. Mol Vis 2008;14:2263-2271.

    External Resources

  25. Sakurada Y, Kubota T, Imasawa M, Mabuchi F, Tanabe N, Iijima H: Association of LOC387715 A69S genotype with visual prognosis after photodynamic therapy for polypoidal choroidal vasculopathy. Retina 2010;30:1616-1621.
  26. Immonen I, Seitsonen S, Tommila P, Kangas-Kontio T, Kakko S, Savolainen ER, Savolainen MJ, Liinamaa MJ: Vascular endothelial growth factor gene variation and the response to photodynamic therapy in age-related macular degeneration. Ophthalmology 2010;117:103-108.
  27. Tsuchihashi T, Mori K, Horie-Inoue K, Gehlbach PL, Kabasawa S, Takita H, Ueyama K, Okazaki Y, Inoue S, Awata T, Katayama S, Yoneya S: Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration. Ophthalmology 2011;118:93-100.
  28. 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;114:2168-2173.
  29. Lee AY, Raya AK, Kymes SM, Shiels A, Brantley MA Jr: Pharmacogenetics of complement factor H (Y402H) and treatment of exudative age-related macular degeneration with ranibizumab. Br J Ophthalmol 2009;93:610-613.
  30. Nischler C, Oberkofler H, Ortner C, Paikl D, Riha W, Lang N, Patsch W, Egger SF: Complement factor H Y402H gene polymorphism and response to intravitreal bevacizumab in exudative age-related macular degeneration. Acta Ophthalmol 2011;89:e344-e349.
  31. Imai D, Mori K, Horie-Inoue K, Gehlbach PL, Awata T, Inoue S: CFH, VEGF, and PEDF genotypes and the response to intravitreous injection of bevacizumab for the treatment of age-related macular degeneration. J Ocul Biol Dis Infor 2010;3:53-59.
  32. Smailhodzic D, Muether PS, Chen J, Kwestro A, Zhang AY, Omar A, van de Ven JP, Keunen JE, Kirchhof B, Hoyng CB, Klevering BJ, Koenekoop RK, Fauser S, den Hollander AI: Cumulative effect of risk alleles in CFH, ARMS2, and VEGFA on the response to ranibizumab treatment in age-related macular degeneration. Ophthalmology 2012;119:2304-2311.
  33. Nakata I, Yamashiro K, Nakanishi H, Tsujikawa A, Otani A, Yoshimura N: VEGF gene polymorphism and response to intravitreal bevacizumab and triple therapy in age-related macular degeneration. Jpn J Ophthalmol 2011;55:435-443.
  34. Kloeckener-Gruissem B, Barthelmes D, Labs S, Schindler C, Kurz-Levin M, Michels S: Genetic association with response to intravitreal ranibizumab in patients with neovascular AMD. Invest Ophthalmol Vis Sci 2011;52:4694-4702.
  35. McKibbin M, Ali M, Bansal S, Baxter PD, West K, Williams G, Cassidy F, Inglehearn CF: CFH, VEGF and HTRA1 promoter genotype may influence the response to intravitreal ranibizumab therapy for neovascular age-related macular degeneration. Br J Ophthalmol 2012;96:208-212.
  36. Abedi F, Wickremasinghe S, Richardson AJ, Makalic E, Schmidt DF, Sandhu SS, Baird PN, Guymer RH: Variants in the VEGFA gene and treatment outcome after anti-VEGF treatment for neovascular age-related macular degeneration. Ophthalmology 2013;120:115-121.
  37. Boltz A, Ruiss M, Jonas JB, Tao Y, Rensch F, Weger M, Garhöfer G, Frantal S, El-Shabrawi Y, Schmetterer L: Role of vascular endothelial growth factor polymorphisms in the treatment success in patients with wet age-related macular degeneration. Ophthalmology 2012;119:1615-1620.
  38. Lahiri DK, Nurnberger JI Jr: A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 1991;19:5444.
  39. Petrovic MG, Korosec P, Kosnik M, Osredkar J, Hawlina M, Peterlin B, Petrovic D: Local and genetic determinants of vascular endothelial growth factor expression in advanced proliferative diabetic retinopathy. Mol Vis 2008;30:1382-1387.

    External Resources

  40. Renner W, Kotschan S, Hoffmann C, Obermayer-Pietsch B, Pilger E: A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels. J Vas Res 2000;37:443-448.
  41. Lai TY, Chan WM, Liu DT, Luk FO, Lam DS: Intravitreal bevacizumab (Avastin) with or without photodynamic therapy for the treatment of polypoidal choroidal vasculopathy. Br J Ophthalmol 2008;92:661-666.
  42. Mitamura Y, Kitahashi M, Kubota-Taniai M, Yamamoto S: Comparison of intravitreal bevacizumab to photodynamic therapy for polypoidal choroidal vasculopathy: short-term results. Indian J Ophthalmol 2010;58:291-296.
  43. Fung AE, Lalwani GA, Rosenfeld PJ, Dubovy SR, Michels S, Feuer WJ, Puliafito CA, Davis JL, Flynn HW Jr, Esquiabro M: An optical tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 2007;143:566-583.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50