Optical coherence tomography angiography in Alzheimer's disease: a systematic review and meta-analysis

Background To assess the association between optical coherence tomography angiography (OCTA) retinal measurements and Alzheimer's disease (AD). Methods We searched MEDLINE and EMBASE from inception up to October 28th, 2020 for studies assessing the association between OCTA retinal measurements and AD. Estimates from eligible studies were meta-analysed and pooled standardized mean differences (SMDs) between AD patients and healthy participants with corresponding 95% confidence intervals (95% CI) were calculated, using the Hartung-Knapp/Sidik-Jonkman random-effects method. In addition, we quantified the minimum strength on the risk ratio scale (E value) required for an unmeasured confounder to nullify these associations. Results Ten eligible studies for our systematic review were identified through our search strategy. The pooled SMD between the retinal vessel density of AD patients and healthy participants in the whole superficial vascular plexus (SVP), parafoveal SVP and foveal avascular zone (FAZ) was -0.41 (95% CI: -0.69 to -0.13, p value = 0.01, I-2 = 15%, seven studies), -0.51 (95% CI: -0.84 to -0.18, p value = 0.01, I-2 = 40%, six studies), and 0.87 (95% CI: -0.03 to 1.76, p value = 0.05, I-2 = 91%, seven studies), respectively. An unmeasured confounder would need to be associated with a 2.26-, 2.56- and 3.82-fold increase in the risk of AD and OCTA retinal measurements, in order for the pooled SMD estimate of vessel density in whole SVP, parafoveal SVP and FAZ, respectively, to be nullified. Conclusions In our study, whole and parafoveal SVP vessel density were inversely associated with AD. However, prospective longitudinal studies with larger sample sizes are needed to furtherly assess these associations.