Association Between Response to Intravitreal Ranibizumab and Known AMD Susceptibility Loci in Age-Related Macular Degeneration

Abstract

Purpose: : Recent studies revealed different responses to anti VEGF treatment in patients with neovascular AMD, despite similar baseline characteristics and comparable treatment regimens. We evaluated a possible relationship between treatment outcome and the individual’s genetic background.

Methods: : Clinical data of neovascular AMD patients treated with intravitreal Ranibizumab were collected during a period of at least 12 months. Percentiles of the visual acuity were calculated at month 12. Genotypes for five SNPs, which previously had been shown to be involved in AMD, were determined by DNA sequencing or the Taq-man SNP assay. From the assessment of the course of visual acuity two groups were created: 75^th percentile (good responders) and 25^th percentile (bad responders). Genotypes for SNPs rs1061170 in CFH, rs641153 in CFB, rs11200638 in HTRA1, rs10490924 in LOC387715 and rs1413711 in VEGFA from individuals of these two groups were analyzed.

Results: : We did not find an association between treatment outcome and the allele frequency of the five loci. In contrast, one genotype of CFH was found at a significantly higher frequency in patients that did not respond well to the treatment compared to those that responded well. The difference was statistically significant, yielding an odds ratio of 2.8.

Conclusions: : At this time, a promising trend of association of complement factor H with outcome of treatment supports our hypothesis. Patients with this particular genotype are approximately 3 times less likely to experience a successful treatment. Improved treatment regimens may result from these studies.

Keywords: age-related macular degeneration • genetics • clinical (human) or epidemiologic studies: outcomes/complications