European investigators led by Eliana Costanzo, MD, reported that more work needs to be done to identify ocular biomarkers of early Alzheimer’s disease mild cognitive impairment. The ocular biomarkers studied showed poor to moderate accuracy for detecting the 2 disorders.¹

Costanzo is from IRCCS-Fondazione Bietti, Rome, Italy.

The investigators from across Europe conducted an meta-analysis of 14 cross-sectional studies that included findings obtained by optical coherence tomography (OCT) peripapillary retinal nerve fiber layer thickness, OCT angiography (OCTA), foveal avascular zone measurement, and prosaccade latency of saccadic eye movements.

The main outcome measure is the accuracy of ocular biomarkers for diagnosing Alzheimer’s disease and mild cognitive impairment in patients in secondary care or memory clinics.

Data analysis results

The investigators identified 591 reports that included 14 systematic reviews (median, range number of studies in each review, 14, 5-126), only 4 of which were at low risk of bias on all Risk of Bias in Systematic Reviews domains.

The authors reported that the imaging-derived parameters with the most evidence for detecting Alzheimer’s disease compared with healthy controls were OCT peripapillary retinal nerve fiber layer thickness (38 studies that included 1883 patients with Alzheimer’s disease and 2510 controls; area under the curve [AUC ], 0.70; 95% confidence interval [CI], 0.53-0.79); the OCTA foveal avascular zone (5 studies that included 177 patients with Alzheimer disease and 371 controls; AUC , 0.73; 95% CI, 0.50-0.89); and the saccadic eye movement prosaccade latency (30 studies that included 651 patients with Alzheimer disease and mild cognitive impairment and 771 controls; AUC , 0.64; 95% CI, 0.58-0.69).

The anti-saccade error was investigated in only12 studies that included 424 patients with Alzheimer disease and mild cognitive impairment and 382 controls) and yielded the best accuracy (AUC , 0.79; 95% CI, 0.70-0.88).

“This umbrella review has highlighted limitations in design and reporting of the existing research on ocular biomarkers for diagnosing Alzheimer disease,” the investigators concluded. “The parameters with the best evidence showed poor to moderate diagnostic accuracy in cross-sectional studies. Future longitudinal studies should investigate whether changes in OCT and OCTA measurements over time can yield accurate predictions of Alzheimer disease onset.”

Reference

1 Costanzo E, Lengyel I, Paravano M, et al. Ocular biomarkers for Alzheimer disease dementia. JAMA Ophthalmol. Published online November 17, 2022. doi:10.1001/jamaophthalmol.2022.4845