Anti-VEGF injections linked to cognitive decline

Researchers who examined the cognitive health of patients who received repeated intravitreal injections of vascular endothelial growth factor (anti-VEGF) found that those who received higher numbers of injections had a significantly increased likelihood of mild cognitive impairment than Patients who did not receive anti-VEGF. However, these results, published in Retina, could 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 the researchers.

The researchers recruited 175 patients between the ages of 65 and 85 with vision of at least 20/50 or better in one eye and a diagnosis of AMD. Study participants performed an iPad-based brain health assessment (BHA) to determine the risk of mild cognitive impairment. The result for each patient was compared to the total number of anti-VEGF injections per individual patient. The patients were then divided into groups of 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 had mean scores suggesting a low likelihood of mild cognitive impairment (BHA = -0.99Z). In contrast, the patient groups are grouped with an increasing number of anti-VEGF injections [1-9 IVI (n=44), 10-20 (n=20), >20 IVI (n=58)] averaged correspondingly poorer BHA values ​​(-1.12Z, -1.16Z or -1.38Z), which indicates a higher probability of a slight cognitive impairment. The results for all 4 BHA subgroup tests – memory, executive function and speed, visual and verbal – worsened along with increased cumulative injection numbers, according to the study.

The vitreous-retinal-choroidal complex lies next to the optic nerve, which is inside the sheath of the central nervous system. According to the study’s researchers, it is unknown whether the normal barriers between the vitreous complex and the central nervous system are compromised by repeated intravitreal anti-VEGF injections.

While this study was not designed to show a causal link between injections and cognitive decline, the researchers say the results suggest that additional study is needed.

One of the limitations of the study is that there was no pre-defined schedule for patients who received anti-VEGF injections. The study is also limited by its retrospective cross-sectional design and the many confounding factors that can affect both eyesight and cognitive health.


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

This article originally appeared on Ophthalmology Advisor

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