Anti-VEGF Injections Associated with Cognitive Impairment in AMD Patients

Subhransu K. Ray, MD, PhD

Intravitreal anti-VEGF is associated with greater rates of cognitive impairment, according to findings of a new cross-sectional study.

In a new trial presented at the American Society of Retina Specialists (ASRS) 2020 Virtual Meeting this weekend, study author Subhransu K. Ray, MD, PhD, of Sutter Health, and colleagues found that the role between vascular endothelial growth factor (VEGF) and central nervous system (CNS) health may be pronounced in the use of the most popular therapy for neovascular age-related macular degeneration (nAMD).

The interim findings could come as a raised concern for the retina care community, as millions of intravitreal anti-VEGF administrations are given annually to a mostly older patient population.

“Despite the fact that millions of intravitreal injections are performed yearly in the United States, and that these agents can be found in systemic circulation, there have been no formal studies assessing the cognitive impact of these repeated injections in these potentially cognitively vulnerable age group,” Ray explained in a presentation.

Noting a direct communication between the CNS and vitreous across multiple pathological states, investigators sought to interpret the actual effect anti-VEGF injection therapy may have on the cognitive health of patients with nAMD.

Their cross-sectional analysis compared the Brain Health Assessment (BHA) scores of patients with AMD aged 65-85 years old in relation to lifetime cumulative count of anti-VEGF injections. BHA scores were assessed via the University of California San Francisco’s peer-validated metric, often used for the initial detection of mild neurocognitive disorders.

A group of 300 wet AMD (≥1 IV anti-VEGF injections) and 100 dry AMD (0 inections) patients underwent a 10-minute iPad test gauging their individual and composite age-corrected scores for executive function, as well as speed, language, visuospatial, and memory tests.

Patients with previously known history of CNS disorders were excluded from the trial. The ASRS-presented findings were an interim analysis of the first 116 enrolled patients.

Ray and colleagues observed a statistically significant difference in patient BHA scores (t[116] = 2.03; P <.05), indicating a greater rate of cognitive impairment among those who received >20 anti-VEGF injections.

The 72 patients with <20 injections reported significantly healthier BHA scores than the 44 with ≥20 injections. Investigators also noted a greater likelihood of cognitive impairment among patients with ≥20 injections than those with fewer.

The team concluded their preliminary findings show a greater risk of cognitive impairment among frequent recipients of anti-VEGF injections for AMD, indicating the need for cognitive assessment tools in clinical retina settings.

That said, the finding was correlative, not causal. Further validation through independent cognitive tools and assays may be warranted.

“We also have a prospective trial underway with patients actively initiating anti-VEGF injections,” Ray said. “Those patients will be assessed at 6 months and 12 months following initial intravitreal injection.”

Investigators added that due to the frequency of intravitreal injections being performed in a cognitively at-risk population, the potential channels of communication between the vitreous and brain, and the role of VEGF in CNS health, more analysis is suggested.

The study, “Cognitive Testing in Patients Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Therapy for Wet Age-Related Macular Degeneration,” was presented at ASRS 2020.