After intravitreal injection, anti–vascular endothelial growth factor (VEGF) agents are found in the systemic circulation and can suppress systemic VEGF levels. Neuronal health and cognitive function in the central nervous system have been associated with normal physiological levels of VEGF expression. We wished to determine whether there was an association between cumulative anti-VEGF exposure and cognitive function.
One hundred and seventy-five patients aged 65 to 85 with vision of at least 20/50 or better in one eye and a diagnosis of age-related macular degeneration took an iPad-based brain health assessment to determine their risk of mild cognitive impairment. The result for each patient was compared with the total number of anti-VEGF injections per individual patient. Patients were then stratified into groups with 0 injections (control), 1 to 9 injections, 10 to 20 injections, or greater than 20 injections.
The group of patients with more than 20 injections had a higher likelihood of mild cognitive impairment compared with the control group, with statistically significant worse mean Z-scores (P = 0.04).
Our study is the first to associate worsening cognitive health with higher cumulative anti-VEGF injections. This study was not designed to show a causal link, but does suggest that additional investigation is warranted.