More frequent anti-VEGF injections in AMD linked to increased cognitive impairment risk
Researchers linked higher frequency of intravitreal anti-VEGF injections with a greater risk for mild cognitive impairment in patients with age-related macular degeneration.
“There have been no formal studies assessing the cognitive impact of these repeated injections in a potentially cognitively-vulnerable age group,” Subhransu K. Ray, MD, PhD, of Bay Area Retina Associates, said in his presentation at the virtual American Society of Retina Specialists meeting. “Although we do know the vitreous communicates directly to the CNS in various pathological states, we know very little of the impact of repeated intravitreal injections and the integrity of the normal barriers between vitreous cavity and the CNS.”
Ray and colleagues conducted a cross-sectional study comparing the cognition scores of patients aged 65 to 85 years in relation to their lifetime cumulative number of injections to determine the impact of repeated intravitreal anti-VEGF injections on cognitive health in neovascular AMD.
To evaluate cognitive function, the researchers used University of California, San Francisco’s BHA, a 10-minute iPad-based test that provides individual and composite age-corrected scores of executive function and speed, language, visuospatial and memory tests. The study design included 300 wet AMD (1 IVI) and 100 dry AMD (0 IVI) patients.
Ray said these results showed that patients with higher cumulative doses of anti-VEGF injections performed statistically worse on BHA testing, which suggests of a higher likelihood of mild cognitive impairment.
Results from the interim analysis of the first 116 patients enrolled in the study demonstrated a statistically significant difference in patient BHA scores (t[116] = 2.03; P < .05), which indicated a greater prevalence of cognitive impairment in patients who received more than 20 intravitreal injections. Moreover, analysis showed significantly healthier BHA scores in the 72 patients who received fewer than 20 intravitreal injections compared with the 44 patients who received more than 20 injections.
BHA z scores describe the likelihood of cognitive impairment – less than -1.5 z equals high risk, -1.5 z to -1 z equals moderate risk and more than -1 z equals low risk, according to the presentation. On average, the z score for the group who received less than 20 injections was -0.83 and the score for the group who received 20 or more injections was –1.27 (P < .05).
The results also showed that patients who received no intravitreal injections had a 27.6% risk for cognitive impairment (n = 29), those who received 1 to 20 injections had a 31.8% risk (n = 44) and those who received more than 20 injections had a 41.9% risk (n = 43).
“This study did not assess a causal link, but rather demonstrated an association between higher treatment number and higher risk of mild cognitive impairment,” he said. “This study needs to be validated using other, independent cognitive tools and assays. Future directions should include targeted neuroimaging careful examinations of optic nerve integrity prior to and following repeated intravitreal injections as well as re-examination of preclinical data.”
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Ray SK, et al. Cognitive Testing in patients receiving intravitreal anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Presented at: American Society of Retina Specialists annual meeting; July 24-26, 2020 (virtual meeting).