Brain Health Assessment in Macular Degeneration Patients Undergoing Intravitreal Anti–vascular Endothelial Growth Factor Injections (The Bham Study)

Abstract

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.Methods: 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 iPadbased 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.Results: 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).Conclusion: 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.

VEGF Paradoxically Reduces Cerebral Blood Flow in Alzheimer’s Disease Mice

“…Indeed, increased exposure to anti-VEGF-A injections could place patients at greater risk for impaired neuroprotection. Of note, those receiving 15 to 20 injections did not demonstrate a higher likelihood of cognitive impairment, 31 this could further support the need of a vascular specific VEGF-A inhibition.…”

“…For example the repetitive treatment increases the risk for hypertension-induced brain hemorrhages 30 and maybe even cognitive decline. 31 …”

“…Images taken from Ali et al 19 For example the repetitive treatment increases the risk for hypertension-induced brain hemorrhages 30 and maybe even cognitive decline. 31 A study analyzed 175 patients undergoing anti-VEGF-A treatment for macular degeneration demonstrated those with 20 or more injections had a higher likelihood of mild cognitive impairment as calculated on an iPad-based brain health assessment. 31 In our study mice were administered at most 6 anti-VEGF-A injections over the course of 2 weeks.…”

“…31 A study analyzed 175 patients undergoing anti-VEGF-A treatment for macular degeneration demonstrated those with 20 or more injections had a higher likelihood of mild cognitive impairment as calculated on an iPad-based brain health assessment. 31 In our study mice were administered at most 6 anti-VEGF-A injections over the course of 2 weeks. 19 Given the intraperitoneal mode of injection and size of the antibody used in our experiments, we largely saw effects on the vascular system rather than the brain parenchyma itself.…”

Brolucizumab for the treatment of diabetic macular edema

“…Not only are frequent intravitreal anti-VEGF injections uncomfortable, but the cumulative exposure of intravitreal injections (IVI) can also result in adverse effects with long term use [16,17], such as increased risk of endophthalmitis, subconjunctival hemorrhage, retinal pigment epithelial tears, and retinal detachment [18][19][20]. Even recent studies showcasing the efficacy of brolucizumab for use in nAMD demonstrate risks for intraocular inflammation (IOI), with rates as high as 4.6% [21].…”