Cumulative Effect of Risk Alleles in CFH, ARMS2, and VEGFA on the Response to Ranibizumab Treatment in Age-related Macular Degeneration

Smailhodzic, Dženita; Muether, Philipp S.; Chen, John; Kwestro, Angela; Zhang, Alice Yang; Omar, Amer; Ven, Johannes P. H. van de; Keunen, Jan E.E.; Kirchhof, Bernd; Hoyng, Carel B.; Klevering, B. Jeroen; Koenekoop, Robert K.; Fauser, Sascha; Hollander, Anneke I. den

doi:10.1016/j.ophtha.2012.05.040

Cited by 102 publications

(85 citation statements)

References 33 publications

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“…Genetic factors are known to play a major role in the pathogenesis of AMD and have been suggested to influence the response to different modalities of AMD therapy, including oral antioxidants, PDT, and anti-VEGF agents [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] . Other authors have studied the effect of the CFH rs1061170 (Y402H) on the response to PDT, with controversial results [10][11][12][13][14] .…”

Section: Discussion Discussion Discussion Discussion Discussionmentioning

confidence: 99%

“…Other have evaluated the relationship between CFH genotypes and photodynamic therapy (PDT), with controversial results [12][13][14][15][16] . The association between gene polymorphisms and response to anti-vascular-endothelial growth-factor (VEGF) therapy for neovascular AMD has also been studied [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] . Intravitreal injections of anti-VEGF agents were the first treatment that consistently improved visual acuity (VA) in a large number of patients, representing a remarkable advance in the treatment of neovascular AMD.…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

“…However, there is a broad range of response rates to anti-VEGF therapy, and genetic variants may be partially responsible 6 . Several reports evaluated CFH genotype association with the response to the anti-VEGF agents bevacizumab and ranibizumab, some of them suggesting a potential pharmacogenetic relationship [17][18][19][20][21][22][23][24][25][26] . The purpose of this study was to investigate the association between CFH Y402H (rs1061170) SNP with response to ranibizumab therapy in neovascular AMD for the first time in a Brazilian population.…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

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CFH Y402H polymorphism and response to intravitreal Ranibizumab in brazilian patients with neovascular age-related macular degeneration

Veloso

Almeida

Nehemy

2014

Rev. Col. Bras. Cir.

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Objective: To investigate the association between CFH gene polymorphism and response to ranibizumab in Brazilian patients with neovascular age-related macular degeneration (AMD).Methods: 95 patients were genotyped for the CFH rs1061170 (Y402H) single nucleotide polymorphism. Patients with neovascular AMD initially received intravitreal ranibizumab injections for three months and were retreated as needed. Visual acuity (VA) and central retinal thickness (CRT) were measured before treatment and at 1, 3, 6, and 12 months post-treatment.Results: For patients with the TT and TC genotypes, paired comparisons of VA showed a statistically significant improvement when the data obtained at all visits were compared with baseline. Patients homozygous for the risk genotype (CC) did not show a statistically significant improvement when VA obtained at visits 1, 3, 6 and 12 were compared with baseline. For all genotypes, paired comparisons of CRT showed a statistically significant improvement when the data obtained at visits 1, 3, 6 and 12 were compared with baseline.Conclusion: Patients with the CC genotype showed poorer long-term functional response to intravitreal ranibizumab.

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Section: Discussion Discussion Discussion Discussion Discussionmentioning

confidence: 99%

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

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CFH Y402H polymorphism and response to intravitreal Ranibizumab in brazilian patients with neovascular age-related macular degeneration

Veloso

Almeida

Nehemy

2014

Rev. Col. Bras. Cir.

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“…Características genéticas, demográficas e clínicas têm sido associadas na literatura com a resposta à terapia antiangiogênica para a DMRIn 6,7,8 . Aspectos morfológicos da TCO também foram propostos como base para uma nova classificação da doença 9 .…”

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Tomographic findings predictive of the anatomic response to ranibizumab in age-related macular degeneration

Evangelista¹,

Honório²,

Leite³

et al. 2018

eOftalmo

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Como citar: Evangelista IWQ; Honório CRC; Leite EP; Eulálio TC. Aspectos tomográficos preditivos da resposta anatômica ao ranibizumabe na degeneração macular relacionada à idade. eOftalmo. 2018: 4(2): 80-85. http://dx.doi.org/10.17545/eoftalmo/2018.0014Objetivo: Este estudo objetivou verificar se características morfológicas à tomografia de coerência óptica de domínio espectral afetam os resultados anatômicos na degeneração macular relacionada à idade neovascular tratada com ranibizumabe. Métodos: Avaliou-se a presença de fluido intrarretiniano, de fluido sub-retiniano, de fluido intrarretiniano associado a fluido sub-retiniano, além de descolamento do epitélio pigmentar da retina, antes do tratamento, e a associação dessas alterações com a ausência de fluido retiniano, após o tratamento. Foram incluídos 22 olhos virgens de tratamento e submetidos a injeções mensais de ranibizumabe. Resultados: Inicialmente, 22,7% dos olhos apresentavam apenas fluido intrarretiniano (grupo 1), 27,2%, apenas fluido sub-retiniano (grupo 2) e 45,4%, combinação de fluidos intrarretiniano e sub-retiniano (grupo 3). Com o tratamento, os percentuais de olhos que se apresentaram sem fluido foram 66,6, 60,0 e 33,3% para os grupos 1, 2 e 3, respectivamente. Nenhum dos olhos com descolamento do epitélio pigmentar associado às alterações iniciais se apresentou sem fluido após o tratamento. Conclusão: Olhos que apresentavam descolamento do epitélio pigmentar inicialmente exibiram a pior resposta anatômica ao tratamento com ranibizumabe. Olhos com a associação de fluidos intrarretiniano e sub-retiniano responderam pior ao tratamento do que aqueles com fluido sub-retiniano ou fluido intrarretiniano como alteração isolada. ABSTRACTObjective: This study aimed to assess whether morphological features observed on spectral domain optical coherence tomography affect anatomical results in patients with neovascular age-related macular degeneration treated with ranibizumab. Methods: Before treatment, we assessed the presence of intraretinal fluid, subretinal fluid, an association between both, and retinal pigment epithelial detachment. After treatment, we assessed the association between these changes and the absence of retinal fluid. Twenty-two virgin eyes were included and underwent monthly injections of ranibizumab. Results: Before treatment, 22.7% of the eyes presented with intraretinal fluid only (group 1), 27.2% exhibited subretinal fluid only (group 2), and 45.4% had a combination of both (group 3). After treatment, 66.6%, 60.0%, and 33.3% of the eyes in groups 1, 2, and 3, respectively, presented no fluid, and none of the eyes with pigment epithelial detachment associated with the initial changes presented no fluid. Conclusion: Eyes with retinal pigment epithelial detachment before treatment had the worst anatomical response to ranibizumab treatment. Eyes with a combination of both intraretinal and subretinal fluids had a worse response to treatment than those with intraretinal or subretinal fluid alone.Palavras-chave: Degeneração Macular; Rani...

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“…There have been reports that CFH Y402H, ARMS2 rs10490924, HTRA1 rs11206038, and VEGFA polymorphisms are associated with responsiveness to ranibizumab treatment (Lee et al, 2009;Smailhodzic et al, 2012;Boltz et al, 2012;Chang et al, 2013). However, in the CATT and IVAN trials, which were multicentric randomized trials, the authors reported that there were no statistically significant associations between the genetic variants and anti-VEGF responsiveness (Hagstrom et al, 2013(Hagstrom et al, , 2014Lotery et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Effect of ARMS2 gene polymorphism on intravitreal ranibizumab treatment for neovascular age-related macular degeneration

Bardak

Erçalik

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries. The ARMS2 gene has been found to be associated with AMD. Currently, intravitreal ranibizumab (IVR) treatment is one of the widely used treatments for neovascular AMD. The aim of this study was to investigate the association between the genotype of ARMS2 rs10490924 polymorphism and IVR treatment responsiveness in patients with neovascular AMD. The study included 39 patients with advanced neovascular AMD (patient group) and 250 healthy individuals with exome sequencing data (control group). The patient group was divided into three subgroups: GG (N = 10), TG (N = 14), and TT (N = 15). Before IVR treatment, all patients had intraretinal or subretinal fluid or both. They received three monthly IVR-injection treatments. One month after the third injection, the patients were evaluated as either "responders" or "non-responders" based on the presence or absence of intraretinal or subretinal fluid or both. The patient subgroups TG and TT had an 8.56-and 39-fold higher risk of AMD, respectively, than patient subgroup GG had. The allele frequency was 0.537 and 0.10 in the patient and control groups, respectively. Within the patient subgroup TT, there was a significant difference between the "responders" and "non-responders" (P = 0.025). In conclusion, in neovascular AMD patients undergoing IVR treatment, TT genotype tended to be a better predictor of good short-term treatment response, compared to the GG and TG genotypes. Further studies using confirmed genetic biomarkers for individualized optimal treatments are required.

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Cumulative Effect of Risk Alleles in CFH, ARMS2, and VEGFA on the Response to Ranibizumab Treatment in Age-related Macular Degeneration

Cited by 102 publications

References 33 publications

CFH Y402H polymorphism and response to intravitreal Ranibizumab in brazilian patients with neovascular age-related macular degeneration

CFH Y402H polymorphism and response to intravitreal Ranibizumab in brazilian patients with neovascular age-related macular degeneration

Tomographic findings predictive of the anatomic response to ranibizumab in age-related macular degeneration

Effect of ARMS2 gene polymorphism on intravitreal ranibizumab treatment for neovascular age-related macular degeneration

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