• Comprehensive Ophthalmology, Neuro-Ophthalmology/Orbit, Retina/Vitreous

    Review of: OCTA Findings in Pre-Clinical Alzheimer's Disease: 3 Year Follow-Up

    O'Bryhim B, Lin J, Van Stavern G, et al. Ophthalmology, in press

    Investigators longitudinally examined long-term alterations in the foveal avascular zone (FAZ) in patients with preclinical Alzheimer disease. 

    Study design

    The authors conducted a 3-year prospective OCT angiography (OCTA) study of 20 cognitively normal patients, 9 of which had positive biomarkers of preclinical Alzheimer disease (positive amyloid PET scan and/or cerebrospinal fluid analysis), while 11 were biomarker negative. 


    At 3-year follow-up, only 1 patient developed mild dementia while the rest of the subjects had no detectable cognitive changes. As found in the original baseline study, the FAZ remained enlarged in biomarker-positive eyes compared with biomarker-negative eyes (0.368 vs 0.272 mm2, P=0.03). However, there was no significant change in the FAZ between groups over the study period. Additionally, the authors did not observe differences in any other structural measurements of the retina, including the retinal nerve fiber or ganglion cell layers. 


    The main limitation is the relatively small sample size of 20 patients, which may be underpowered to detect subtle anatomic longitudinal changes in preclinical Alzheimer’s disease.

    Clinical significance

    This study shows that the FAZ remains enlarged in patients with preclinical AD, suggesting OCTA can be used to help identify patients susceptible to developing Alzheimer disease. However, the rate of change is slow and no detectable differences were observed over a 3-year period in a cohort of patients that mostly remained without cognitive deficits. These findings support the idea that the preclinical period of Alzheimer disease can occur over an extended period of time.