Purchase this article with an account.
C. F. Inglehearn, M. Ali, P. D. Baxter, S. Bansal, K. West, G. A. Williams, F. Cassidy, M. McKibbin; Htra1 Promotor Snp Rs11200638 Genotype and Sex Predict Response to Ranibizumab Treatment in Age-Related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2010;51(13):2782.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
AMD, the commonest cause of blindness in the developed world, was until recently untreatable. However several therapies have now been developed, the most successful of which is the anti-VEGF Fab fragment ranibizumab (Lucentis). Treatment stabilises or improves visual acuity in most patients but a small proportion continue to lose vision. Much of the genetic basis of AMD susceptibility is known. We therefore tested whether genotypes for three SNPs strongly associated with AMD could also predict response to treatment.
142 AMD patients being treated with ranibizumab (0.5mg with a loading phase of 3 injections followed by treatment as required in a maintenance phase) were recruited, a blood sample was taken and visual acuity in ETDRS letters measured pre-treatment and again every month thereafter for 6 months. Smoking history, previous treatment, age, sex and number of injections were recorded. Genotypes were obtained for rs11200638 near HTRA1, rs1061170 in CFH and rs1413711 in VEGF. Data were analysed with treatment response as both a binary (>5 letters improvement at 6 months vs ≤ 5 letter gain) and quantitative trait.
With response as a binary trait, women responded better than men to treatment at three months (p=0.0328), but genotypes and other variables were not significantly predictive. With response as a quantitative trait, SNP rs11200638 near HTRA1 was significantly associated with treatment outcome at 6 months (p=0.0214). Homozygotes for the low AMD-risk allele G had a poor response (mean improvement 0.15 ETDRS letters), whereas mean improvement for the AG genotype was 7.3 letters and for AA 3.8 letters.
We report tentative evidence that sex and HTRA1 SNP genotype may influence the short-term response to treatment with ranibizumab. The ability to predict which patients will respond to treatment could save sight by redirecting poor responders to other therapies, as well as saving the cost and distress of unsuccessful treatment. However, replication in other and larger series is required.
Clinical Trial: :
EudraCT number 2008-007319-33
This PDF is available to Subscribers Only