Because current research remains conflicted on the role genetics play in treatment response to anti–vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (AMD), researchers used a multicenter genome-wide association study to help clarify the link.

An international team looked at the genetic makeup of 2,058 patients with neovascular AMD, and compared it with their treatment response to a loading dose of three monthly injections of bevacizumab or ranibizumab. The mean visual acuity (VA) gain after the loading dose was 5.1 (13.9) Early Treatment Diabetic Retinopathy ETDRS score letters, or a one-line gain. Genetic analysis revealed no associations between treatment response and any of the previously reported genetic variants. “Our results support the notion that none of the previously identified genetic markers are individually strong determinants of overall functional treatment response,” the researchers said.

However, when they looked at rare variants, the investigators found rare protein-altering variants in the C10orf88 and UNC93B1genes were associated with a worse treatment response—patients with these variants lost a mean VA of 6.09 lines and 5.29 lines, respectively, after three months of anti-VEGF treatment.

“The association of rare variants with VA outcome after treatment was very large, making these findings potentially relevant for the clinical practice,” the study concluded. “These results require further validation in other cohorts.”

Lorés-Motta L, Riaz M, Grunin M, et al. Association of genetic variants with response to anti–vascular endothelial growth factor therapy in age-related macular degeneration. JAMA Ophthalmol. May 31, 2018. [Epub ahead of print].