Association between CFH, CFB, ARMS2, SERPINF1, VEGFR1 and VEGF polymorphisms and anatomical and functional response to ranibizumab treatment in neovascular AMD

Session Details

Session Title: Free Paper Session 9: AMD III

Session Date/Time: Friday 08/09/2017 | 08:00-09:30

Paper Time: 08:06

Venue: Room 117

First Author: : E.Cobos Martín SPAIN

Co Author(s): :    S. Recalde   L. Arias   A. Garcia-Layana   C. Barreales   M. Hernandez-Sanchez   P. Fernandez-Robredo              

Abstract Details

Purpose:

We sought to determine if specific genetic single nucleotide polymorphisms influence vascular endothelial growth factor inhibition response to ranibizumab in a retrospective cohort of Spanish neovascular AMD patients

Setting:

A retrospective, observational, multicentre, cohort study conducted in 6 Spanish Hospitals with 12 months of follow-up

Methods:

A total of 403 Caucasian patients diagnosed with exudative AMD were included in this retrospective multicentre study. After a three-injection loading phase, a pro re nata regimen was followed. Nine SNPs from 6 different genes (CFH, CFB, ARMS2, SERPINF1, VEGFR1, VEGF) were genotyped. Non-genetic risk factors, (gender, smoking habit, and hypertension) were also assessed. Patients were classified as good or poor responders (GR or PR) according to functional (visual acuity), anatomical (foveal thickness measured by OCT), and fluid criteria (fluid/no fluid measured by OCT) after the loading phase and after 12 months of treatment

Results:

Hypertension was the environmental factor with the strongest PR association with ranibizumab response in the anatomical measure after the loading phase (p=0.0004; OR 3.7; 95% CI, 2.4-5.8) and after 12 months of treatment (p=10-5; OR 2.3; 95% CI, 1.5-3.4). The genetic variants rs12614 (CFB), rs699947 (VEGFA) and rs7993418 (VEGFR1) predisposed patients to a GR while rs12603486 and rs1136287 (SERPINF1) were associated with a PR. The protective genotype (AA) of rs800292 variant (CFH) was also associated with a poor anatomical response (p 0.0048).They had better pre-treatment visual acuity than patients with other genotypes (AG/GG), but their response to ranibizumab was significantly inferior in terms of visual acutiy after the loading phase. They improve more gradually than patients with AG/GG genotypes, who have an intense response during the firsts 3 months of treatment, with a final stabilization. Nevertheless, their final visual acuity at 12 months was worse than patients with AA genotype.

Conclusions:

In this cohort of Spanish patients with neovascular AMD, SERPINF1 variants seem to be important SNPs associated with functional and anatomical response to ranibizumab. Protective genotype of CFH was associated with a poor response. Hypertension was also predictive of a poor response to ranibizumab treatment. All these data suggest that genetics play an important role in treatment response in AMD patients

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