Predicting Non-response to Ranibizumab in Patients with Neovascular Age-related Macular Degeneration

Abstract

Purpose: To validate known and to determine new predictors of non-response to ranibizumab in patients with neovascular age-related macular degeneration (AMD) and to incorporate these factors into a prediction rule.

Methods: This multicenter, observational case series study included 394 patients treated with ranibizumab for neovascular AMD. We performed genetic analysis for single nucleotide polymorphisms in AMD-associated genes and collected questionnaires regarding environmental factors and disease history. The primary outcome was non-response to treatment, which we defined as a loss of visual acuity of 30% of letters or more on EDTRS chart.

Results: Of the 394 patients, 47 were classified as non-responder. Independent predictors for non-response were: age, baseline visual acuity, diabetes mellitus and accumulation of risk alleles in the CFH, ARMS2 and VEGF-A genes. The area under the receiver operating characteristic curve was 0.77 (95% confidence interval: 0.70 - 0.84). We derived a clinical prediction rule, with possible total risk scores ranging from 0 to 21 points. The absolute risk of non-response varied from 2% to 53% between risk score groups.

Conclusions: A straightforward clinical prediction rule can aid clinicians identifying AMD patients with an increased or decreased likelihood of non-response to treatment with ranibizumab.

Keywords: 412 age-related macular degeneration • 466 clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials