ABSTRACT NUMBER - 2404

VARIANTS IN THE HTRA1 AND ARMS2 GENES AND OUTCOME OF ANTI-VEGF TREATMENT IN NEOVASCULAR AMD


Farshad Abedi, Sanjeewa Wickremasinghe, Andrea J Richardson, Fakir A Islam, Robyn H Guymer, Paul N Baird

Meeting:  2012 RANZCO


SESSION INFORMATION

Date: 27 Nov 2012

Session Title: FREE PAPERS

Session Time: 2:00 pm - 3:30 pm

Purpose:
To determine the association of genetic variants in known age-related macular degeneration (AMD) risk associated genes with outcome of anti-VEGF treatment in neovascular AMD.

Methods:
224 consecutive patients with neovascular AMD were treated with as required regimen, based upon clinicians’ decision. Seventeen single nucleotide polymorphisms (SNPs) in known AMD risk associated genes including CFH, HTRA1, CFHR1–5, LOC387715/ARMS2, C3, C2, CFB and F13B were examined. Mul-tivariate analysis was used to determine the role of each SNP in treatment outcome.

Results:
Mean baseline VA was 51 ± 16.8 ETDRS letter scores. The AA genotype at rs11200638 – HTRA1 promoter SNP (p = 0.001) – and GG genotype at rs10490924 (A69S) in LOC387715/ARMS2 (p = 0.002) were significantly associated with poorer VA outcome at 12 months following multiple correction. Mean (±SD) change in VA from baseline in patients with AA genotype at rs11200638 was ?2.9 ± 15.2 letters after 12 months, compared with +5.1 ± 14.1 letters in patients with AG or GG genotypes at this SNP. Patients with either of these genotypes were also significantly more likely to lose greater than 15 letters after 12 months. SNPs rs11200638 and rs10490924 were in high linkage disequilibrium (LD, r2 = 0.92). No other examined SNPs were associated with outcome.

Conclusion:
The HTRA1 promoter SNP (rs11200638) and A69S at LOC387715/ARMS2 were associated with a poorer visual outcome for ranibizumab or bevaci-zumab treatment in neovascular AMD, suggesting strong pharmacogenetic associations with anti-VEGF treatment. This finding could aid in applying more individualized treatment regimens based on patients’ genotype to achieve optimal treatment response in AMD.