Plasma metabolomic associations with treatment response in neovascular age-related macular degeneration

Abstract

Purpose : To assess associations between plasma metabolomic profiles and treatment response to three loading intravitreal anti-vascular endothelial growth factor (VEGF) injections in patients with neovascular age-related macular degeneration (AMD).

Methods : From the prospective, longitudinal study, we included patients with treatment-naïve neovascular AMD undergoing three loading intravitreal anti-VEGF injections. All patients were imaged with the same optical coherence tomography (OCT; Heidelberg) protocol. Images were assessed by two independent graders at baseline and 4-to 6-weeks after the third injection. Treatment response was defined as no evidence of sub- or intra-retinal fluid on OCT one month after the third injection. Fasting blood samples were collected at the time of study enrollment, and metabolomic profiling was conducted using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Multilevel mixed-effects linear modeling accounting for the inclusion of two eyes of the same patients were used to assess associations between plasma metabolites and treatment response. Statistical significance was calculated based on the number of independent tests accounting for 80% variance (ENT80, P value < 0.05/80).

Results : We included 132 eyes of 104 patients, most were female (65.4%) with a mean age of 77.7±8.5 years. Aflibercept was the most commonly used anti-VEGF agent (n=57, 43.2%), followed by bevacizumab (n=34, 25.8%) and ranibizumab (n=34, 25.8%). Fifty-three eyes (40.2%) were considered treatment responders. After adjusting age, gender, smoking, and BMI, multilevel mixed-effects linear analysis showed that two secondary bile acids, taurodeoxycholic acid (TDCA) 3-sulfate and TDCA, were positively associated with treatment response (P=0.0006 and P=0.002, respectively).

Conclusions : Our results suggest that baseline levels of bile acids are associated with positive treatment response to 3-loading anti-VEGF injections. Previous work has shown that bile acids are protective for AMD, and may also be associated with better treatment response. These data thus can contribute to a better understanding of the pathophysiology of diverse responses seen in daily clinical practice.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.