DOI: http://dx.doi.org/10.17305/bjbms.2018.2493 | Full Text: [PDF]

Analysis of the association between CFH Y402H polymorphism and response to intravitreal ranibizumab in patients with neovascular age-related macular degeneration (nAMD)

Nur Afiqah Mohamad, Vasudevan Ramachandran, Patimah Ismail, Hazlita Mohd Isa, Yoke Mun Chan, Nor Fariza Ngah, Norshakimah Md Bakri, Siew Mooi Ching, Fan Kee Hoo, Wan Aliaa Wan Sulaiman, Liyana Najwa Inche Mat, Mohd Hazmi Mohamed

Abstract


Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular form of AMD (nAMD) may be due to polymorphisms in the complement factor H gene (CFH). This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE) regimen. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170) polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49) and non-responder (n = 84) group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018). Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05). Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.


Keywords


Age-related macular degeneration; AMD; complement factor H; CFH; ranibizumab; Y402H; SNP; treatment response

Full Text:

[PDF]

References


Friedman DS, O'Colmain BJ, Munoz B, Tomany SC, McCarty C, de Jong PT, et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 2004;122(4):564-72. https://doi.org/10.1001/archopht.122.4.564.

Klein R, Peto T, Bird A, Vannewkirk MR. The epidemiology of age-related macular degeneration. Am J Ophthalmol 2004;137(3):486-95. https://doi.org/10.1016/j.ajo.2003.11.069.

Klein R, Klein BE. The prevalence of age-related eye diseases and visual impairment in aging: Current estimates. Invest Ophthalmol Vis Sci 2013;54(14):ORSF5-ORSF13.

http:// dx.doi.org/10.1167/iovs.13-12789.

Chan W-M, Lai TYY. Age-related macular degeneration and polypoidal choroidal vasculopathy in Asia. Hong Kong Journal of Ophthalmology 2016;14(1):14-9.

Laude A, Cackett PD, Vithana EN, Yeo IY, Wong D, Koh AH, et al. Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: Same or different disease? Prog Retin Eye Res 2010;29(1):19-29. https://doi.org/10.1016/j.preteyeres.2009.10.001.

CATT Research Group, Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 2011;364(20):1897-908. https://doi.org/10.1056/NEJMoa1102673.

Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355(14):1419-31. https://doi.org/10.1056/NEJMoa054481.

Solomon SD, Lindsley K, Vedula SS, Krzystolik MG, Hawkins BS. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration. Cochrane Database Syst Rev 2014;(8):CD005139. https://doi.org/10.1002/14651858.CD005139.pub3.

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.e55. https://doi.org/10.1016/j.ophtha.2008.10.018.

Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age-Related Eye Disease Study Report Number 3. Ophthalmology 2000;107(12):2224-32.

Dikmetas O, Kadayifcilar S, Eldem B. The effect of CFH polymorphisms on the response to the treatment of age-related macular degeneration (AMD) with intravitreal ranibizumab. Mol Vis 2013;19:2571-8. eCollection 2013.

Baird PN, Islam FM, Richardson AJ, Cain M, Hunt N, Guymer R. Analysis of the Y402H variant of the complement factor H gene in age-related macular degeneration. Invest Ophthalmol Vis Sci 2006;47(10):4194-8. https://doi.org/10.1167/iovs.05-1285.

Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, et al. Complement factor H variant increases the risk of age-related macular degeneration. Science 2005;308(5720): 419-21. https://doi.org/10.1126/science.1110359.

Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, et al. Complement factor H polymorphism in age-related macular degeneration. Science 2005;308(5720):385-9. https://doi.org/10.1126/science.1109557.

Lau LI, Chen SJ, Cheng CY, Yen MY, Lee FL, Lin MW, et al. Association of the Y402H polymorphism in complement factor H gene and neovascular age-related macular degeneration in Chinese patients. Invest Ophthalmol Vis Sci 2006;47(8):3242-6. https://doi.org/10.1167/iovs.05-1532.

Hao XF, Xie LK, Tang YZ, Xie WK, Zhang ZF, Qi YX, et al. Association of complement factor H gene polymorphisms with age-related macular degeneration susceptibility. Int J Clin Exp Pathol 2015;8(3):3186-91. eCollection 2015.

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):2168-73. https://doi.org/10.1016/j.ophtha.2007.09.008.

Kloeckener-Gruissem B, Barthelmes D, Labs S, Schindler C, Kurz-Levin M, Michels S, et al. Genetic association with response to intravitreal ranibizumab in patients with neovascular AMD. Invest Ophthalmol Vis Sci 2011;52(7):4694-702. https://doi.org/10.1167/iovs.10-6080.

Nischler C, Oberkofler H, Ortner C, Paikl D, Riha W, Lang N, et al. Complement factor H Y402H gene polymorphism and response to intravitreal bevacizumab in exudative age-related macular degeneration. Acta Ophthalmol 2011;89(4):e344-9.

https://doi.org/10.1111/j.1755-3768.2010.02080.x.

Veloso CE, Almeida LN, Nehemy MB. CFH Y402H polymorphism and response to intravitreal ranibizumab in Brazilian patients with neovascular age-related macular degeneration. Rev Col Bras Cir 2014;41(6):386-92. https://doi.org/10.1590/0100-69912014006002.

Hata M, Tsujikawa A, Miyake M, Yamashiro K, Ooto S, Oishi A, et al. Two-year visual outcome of ranibizumab in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Graefes Arch Clin Exp Ophthalmol 2015;253(2):221-7. https://doi.org/10.1007/s00417-014-2688-1.

Hagstrom SA, Ying GS, Pauer GJ, Sturgill-Short GM, Huang J, Callanan DG, et al. Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT). Ophthalmology 2013;120(3):593-9. https://doi.org/10.1016/j.ophtha.2012.11.037.

Kitchens JW, Kassem N, Wood W, Stone TW, Isernhagen R, Wood E, et al. A pharmacogenetics study to predict outcome in patients receiving anti-VEGF therapy in age related macular degeneration. Clin Ophthalmol 2013;7:1987-93. https://doi.org/10.2147/OPTH.S39635.

Chen G, Tzekov R, Li W, Jiang F, Mao S, Tong Y. Pharmacogenetics of complement factor H Y402H polymorphism and treatment of neovascular AMD with anti-VEGF agents: A meta-analysis. Sci Rep 2015;5:14517. https://doi.org/10.1038/srep14517.

Francis PJ. The influence of genetics on response to treatment with ranibizumab (Lucentis) for age-related macular degeneration: The Lucentis Genotype Study (an American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc 2011;109:115-56.

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(5):610-3. https://doi.org/10.1136/bjo.2008.150995.

Shah AR, Williams S, Baumal CR, Rosner B, Duker JS, Seddon JM. Predictors of response to intravitreal anti-vascular endothelial growth factor treatment of age-related macular degeneration. Am J Ophthalmol 2016;163:154-66.e8. https://doi.org/10.1016/j.ajo.2015.11.033.

Habibi I, Sfar I, Kort F, Aounallah-Skhiri H, Chebil A, Chouchene I, et al. Y402H polymorphism in complement factor H and age-related macular degeneration in the Tunisian population. Ophthalmic Res 2013;49(4):177-84. https://doi.org/10.1159/000345068.

Yamashiro K, Tomita K, Tsujikawa A, Nakata I, Akagi-Kurashige Y, Miyake M, et al. Factors associated with the response of age-related macular degeneration to intravitreal ranibizumab treatment. Am J Ophthalmol 2012;154(1):125-36. https://doi.org/10.1016/j.ajo.2012.01.010.

Kang HK, Yoon MH, Lee DH, Chin HS. Pharmacogenetic influence of LOC387715/HTRA1 on the efficacy of bevacizumab treatment for age-related macular degeneration in a Korean population. Korean J Ophthalmol 2012;26(6):414-22. https://doi.org/10.3341/kjo.2012.26.6.414.

Chang W, Noh DH, Sagong M, Kim IT. Pharmacogenetic association with early response to intravitreal ranibizumab for age-related macular degeneration in a Korean population. Mol Vis 2013;19:702-9.

Sayed KM, Naito T, Nagasawa T, Katome T, Mitamura Y. Early visual impacts of optical coherence tomographic parameters in patients with age-related macular degeneration following the first versus repeated ranibizumab injection. Graefes Arch Clin Exp Ophthalmol 2011;249(10):1449-58. https://doi.org/10.1007/s00417-011-1672-2.

Yuan D, Yuan D, Liu X, Yuan S, Xie P, Liu Q. Genetic association with response to intravitreal ranibizumab for neovascular age-related macular degeneration in the Han Chinese population. Ophthalmologica 2013;230(4):227-32. https://doi.org/10.1159/000355068.

Park UC, Shin JY, Kim SJ, Shin ES, Lee JE, McCarthy LC, et al. Genetic factors associated with response to intravitreal ranibizumab in Korean patients with neovascular age-related macular degeneration. Retina 2014;34(2):288-97. https://doi.org/10.1097/IAE.0b013e3182979e1e.


Refbacks

  • There are currently no refbacks.





Quick links for Authors:Quick links for Peer Reviewers:
  

Advanced online | Current Issue | Archives | Submit a manuscript | About the Journal

© Association of Basic Medical Sciences of FBIH, 1998-2018. Credits to Public Knowledge Project