Anti-VEGF Injections Associated With Cognitive Decline

3D ocular coherence tomography (OCT) after ranibizumab injection, showing age-related macular degeneration (AMD).
Researchers evaluated the brain health assessment scores of patients who received treatments for AMD.

Researchers evaluating the cognitive health of patients receiving repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections found that those who received a higher number of injections had a significantly increased likelihood of mild cognitive impairment as compared with patients who did not receive anti-VEGF. However, these results, published in Retina, may suggest that the duration or severity of age-related macular degeneration (AMD) is an independent risk factor for cognitive decline rather than the number of injections, according to investigators.

The researchers recruited 175 patients between 65 years and 85 years old with vision of at least 20/50 or better in 1 eye and a diagnosis of AMD. Study participants took an iPad-based brain health assessment (BHA) 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), 1-9 injections, 10-20 injections, or more than 20 injections.

The analysis found that 53 patients with dry AMD and no history of anti-VEGF treatment averaged scores that indicate a low likelihood of mild cognitive impairment (BHA=-0.99Z). In contrast, the patient groups with increasing numbers of anti-VEGF injections [1-9 IVI (n=44), 10-20 (n=20), >20 IVI (n=58)] averaged correspondingly worse BHA scores (-1.12Z, -1.16Z, and -1.38Z, respectively), suggesting a higher likelihood of mild cognitive impairment. Scores for all 4 BHA subgroup tests — memory, executive function and speed, visuospatial, and language — worsened in tandem with increased cumulative injection numbers, according to the study.

The vitreous-retina-choroid complex lies adjacent to the optic nerve, which is located within the sheathing of the central nervous system. According to the study’s investigators, it is unknown whether the normal barriers between the vitreous complex and central nervous system are impacted by repeated intravitreal anti-VEGF injections.

While this study wasn’t designed to show a causal link between injections and cognitive decline, researchers say the findings suggest that additional studies are needed.

Limitations of the study include that there was no predefined timeline for those patients receiving anti-VEGF injections. The study also is limited by its retrospective cross-sectional design and by the many confounding factors that can affect both vision and cognitive health. 


Ray SK, Manz SN. Brain health assessment in macular degeneration patients undergoing intravitreal anti-VEGF injections (the BHAM study) – an interim analysis. Retina. Published online December 16, 2020. doi:10.1097/IAE.0000000000003066