RT Journal Article
SR Electronic
T1 Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration
JF BMJ Open Ophthalmology
JO BMJ Open Ophth
FD BMJ Publishing Group Ltd
SP e000273
DO 10.1136/bmjophth-2019-000273
VO 4
IS 1
A1 Irina Balikova
A1 Laurence Postelmans
A1 Brigitte Pasteels
A1 Pascale Coquelet
A1 Janet Catherine
A1 Azra Efendic
A1 Yoshikatsu Hosoda
A1 Masahiro Miyake
A1 Kenji Yamashiro
A1 ANGEL study group members
A1 Bernard Thienpont
A1 Diether Lambrechts
YR 2019
UL http://bmjophth.bmj.com/content/4/1/e000273.abstract
AB Objective Age-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysis A retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.Results Association with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.Conclusion Identifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.