Aim: Evidence of the relationship between the polymorphism of the complement factor H (CFH) gene at position 402 (Y402H) and the response to the treatment of wet AMD is controversial. The aim of this study was to compare the functional and morphological 1-year evolution of patients with exudative AMD treated with antivascular endothelial growth factor (VEGF) drugs with the CFH Y402H polymorphism in the Brazilian population. Methods: Forty-six patients treated for wet AMD with bevacizumab or ranibizumab in a pro re nata regimen were included. The evolution of best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and the number of injections over 1 year of follow-up were correlated with CFH genotypes. Results: The analysis of variance for the difference between the BCVA denoted as logMAR (logarithm of the minimum angle of resolution) values showed an improvement at 1 year when compared to baseline (p = 0.039). Profile contrast analysis showed that this difference was significant only in the group without the C allele (p = 0.049), without significance in patients presenting with the risk allele (p = 0.241). CRT showed a mean reduction at 1 year compared to baseline (p < 0.001). Significant differences in the profile contrast test were found in the group without the C allele (p < 0.001) and in patients with the risk allele (p = 0.002). No difference was found in the number of injections among the different groups (p = 0.787). Conclusions: The presence of the risk allele of the Y402H polymorphism in the CFH gene was related to a less favorable evolution over 1 year in this sample of the Brazilian population with exudative AMD who were being treated with anti-VEGF drugs. In agreement with similar previous studies, this study concludes that the CFH risk genotypes may affect the disease response to treatment.

Friedman DS, Katz J, Bressler NM, Rahmani B, Tielsch JM: Racial differences in the prevalence of age-related macular degeneration: the Baltimore Eye Survey. Ophthalmology 1999;106:1049-1055.
Instituto Brasileiro de Geografia e Estatística (IBGE) Censo 2010. Brasília, 2010. (accessed 14 December 2015).
Bressler NM, Bressler SB, Fine SL: Age-related macular degeneration. Surv Ophthalmol 1988;32:375-413.
Brown DM, Regillo CD: Anti-VEGF agents in the treatment of neovascular age-related macular degeneration: applying clinical trial results to the treatment of everyday patients. Am J Ophthalmol 2007;144:627-637.
Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, et al: A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci USA 2005;102:7227-7232.
Seddon JM, Silver RE, Kwong M, Rosner B: Risk Prediction for Progression of macular degeneration: 10 common and rare genetic variants, demographic, environmental, and macular covariates. Invest Ophthalmol Vis Sci 2015;56:2192-2202.
Dezidério Sacconi DP, Cabral de Vasconcellos JP, Endo Hirata F, Mac Cord Medina F, Rim PH, Barbosa de Melo M: Evaluation of CFH Y402H polymorphism and CFHR3/CFHR1 deletion in age-related macular degeneration patients from Brazil. Ophthalmic Genet 2016;37:459-461.
Hirata FE, Cabral de Vasconcellos JP, Mac Cord Medina F, Rim PH, Fulco EA, Barbosa de Melo M: Association of LOC387715/ARMS2 (rs10490924) Gene polymorphism with age-related macular degeneration in the Brazilian population. Ophthalmic Genet 2015;36:224-228.
Seddon JM, Francis PJ, George S, Schultz DW, Rosner B, Klein ML: Association of CFH Y402H and LOC387715 A69S with progression of age-related macular degeneration. JAMA 2007;297:1793-1800.
Kepez Yildiz B, Ozdek S, Ergun MA, Ergun S, Yaylacioglu Tuncay F, Elbeg S: CFH Y402H and VEGF polymorphisms and anti-VEGF treatment response in exudative age-related macular degeneration. Ophthalmic Res 2016;56:132-138.
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:e344-e349.
Tian J, Qin X, Fang K, Chen Q, Hou J, Li J, et al: Association of genetic polymorphisms with response to bevacizumab for neovascular age-related macular degeneration in the Chinese population. Pharmacogenomics 2012;13:779-787.
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;52:4694-4702.
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.
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;109:115-156.
Orlin A HD, Chang W, Ho AC, Brown G, Kaiser RS, Regillo CD, Godshalk AN, Lier A, Kaderli B, Stambolian D: Association between high-risk disease loci and response to anti-vascular endothelial growth factor treatment for wet age-related macular degeneration. Retina 2012;32:4-9.
Mac Cord Medina F, Alves Lopes da Motta A, Takahashi WY, Carricondo PC, Martins dos Santos Motta M, Barbosa de Melo M, et al: Pharmacogenetic effect of complement factor H gene polymorphism in response to the initial intravitreal injection of bevacizumab for wet age-related macular degeneration. Ophthalmic Res 2015;54:169-174.
Hyman L, Neborsky R: Risk factors for age-related macular degeneration: an update. Curr Opin Ophthalmol 2002;13:171-175.
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.
Augustin AJ, Kirchhof J: Inflammation and the pathogenesis of age-related macular degeneration. Expert Opin Ther Targets 2009;13:641-651.
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;308:419-421.
Skerka C, Lauer N, Weinberger AA, Keilhauer CN, Suhnel J, Smith R, et al: Defective complement control of factor H (Y402H) and FHL-1 in age-related macular degeneration. Mol Immunol 2007;44:3398-3406.
Spaide RF, Laud K, Fine HF, Klancnik JM Jr, Meyerle CB, Yannuzzi LA, et al: Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina 2006;26:383-390.
Holz FG, Amoaku W, Donate J, Guymer RH, Kellner U, Schlingemann RO, et al: Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular age-related macular degeneration: the SUSTAIN study. Ophthalmology 2011;118:663-671.
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;41:386-392.
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;120:593-599.
Cruz-Gonzalez F, Cabrillo-Estevez L, Rivero-Gutierrez V, Sanchez-Jara A, De Juan-Marcos L, Gonzalez-Sarmiento R: Influence of CFH, HTRA1 and ARMS2 polymorphisms in the response to intravitreal ranibizumab treatment for wet age-related macular degeneration in a Spanish population. Int J Ophthalmol 2016;9:1304-1309.
Gangnon RE, Lee KE, Klein BE, Iyengar SK, Sivakumaran TA, Klein R: Effect of the Y402H variant in the complement factor H gene on the incidence and progression of age-related macular degeneration: results from multistate models applied to the Beaver Dam Eye Study. Arch Ophthalmol 2012;130:1169-1176.
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