Session Title: Free Paper Session 22: AMD V
Session Date/Time: Sunday 10/09/2017 | 08:00-09:30
Paper Time: 08:30
Venue: Room 115
First Author: : A.Bures Jelstrup SPAIN
Co Author(s): : R. Navarro E. Pomares B. Corcostegui
The aetiology of age-related macular degeneration (AMD) is not completely understood, and the molecular basis of the disease is gaining increasing interest. Neovascular AMD (wAMD) is a subtype of AMD with a very evident VEGF-driven choroidal neovascularization development. The main objective of our investigation consisted on determining the genetic variants of the VEGF pathway (Single Nucleotide Polymorphisms -SNPs- located in the coding and/or regulatory regions of the genes in the VEGF pathway) and their relationship with the efficacy of treatment with intravitreal (IVT) aflibercept (patients that gained ≥ 15 letters at week 52 vs baseline).
Multicentre, phase IV study
The study enrolled a total number of 193 patients from 24 clinical sites across Spain. All patients showed naïve wAMD at presentation with best-corrected visual acuities (BCVA) ranging between 20/320 and 20/40. All patients were treated with IVT afliberceptfor one year according to label for wAMD. After completion of the first year of treatment, patients were offered to continue for a second year, this time following a treat and extend regimen. The results we are presenting are those from the first 12 months of treatment. As for the genetic analysis, a total of 339 SNPs were selected from 89 AMD-associated genes. These genes mostly correspond to the VEGF pathway (VEGFA, VEGFB, VEGFR1, VEGFR2, PIGF, C2, C3, CFH among others). The main criteria used for SNP selection were: location in the coding regions of the gene, minor allele frequency (MAF) greater than 0,30 and previous association with AMD according to literature. The SNP genotyping was performed in a high-throughput platform, which generated raw data genotypes of the 193 treated patients.
169 of the initial 193 subjects were available for BCVA testing at week 52. 57 patients (32,95%) presented BCVA gains ≥ 15 letters. Among all SNPs that appeared significant in the univariate analysis, six entered in the multivariate logistic regression model (rs12366035_VEGFB, rs17793056_CX3CR1, rs1800775_CETP, rs2069845_IL6, rs25681_C5, rs13900_CCL2). Some genetic variations in these SNPs, that presented significant correlation with treatment efficacy (defined as increase in VA ≥ 15 letters), were observed. The most relevant finding was in the SNP rs12366035, located in the VEGFB gene: the TT genotype was found to increase 216.9 times the probability of treatment efficacy compared to the CC genotype.
Our logistic regression model showed ten genotype combinations distributed in six SNPs demonstrating an increase in the probability of better treatment efficacy (measured by an increase in BCVA ≥ 15 letters at week 52). From these correlations, the most remarkable genetic variation is the SNP rs12366035 TT genotype against the CC genotype, as the TT genotype increases 216.9 times the probability of presenting a significant improvement in BCVA. This SNP is found in the gene that regulates VEGFB transcription, indicating that VEGFB probably has a significant role in the response of wAMD to IVT aflibercept, in our studied population.