The possible role of Optical Coherence Tomography (OCT) and OCT‐Angiography (OCTA) as new non‐invasive biomarkers of prodromal Alzheimer’s disease

Several papers support the existence of a possible link between reduced retinal thickness and Alzheimer’s disease (AD) [1]. Other explorative studies based on retinal oximetry and Doppler flowmetry suggest an alteration of retinal perfusion in AD [2, 3]. Nowadays, retina layers and retinal perfusion can be studied by means of non invasive techniques, ie, Optical Coherence Tomography (OCT) and OCT‐Angiography (OCT‐A). So far, data on OCT‐A in AD patients are scarce, conflicting [4‐5] and refer mostly to the dementia phase. Here, we have compared the retinal thickness and the perfusion index, measured by means of OCT and OCT‐A, in patients with mild cognitive impairment showing a CSF profile compatible with AD (MCI‐AD), and age‐matched cognitively healthy controls. We enrolled 37 subjects, 24 MCI‐AD patients, and 13 sex and age‐matched cognitively healthy subjects as control group. The mean age was 69.8 in MCI‐AD and 73.6 in controls. The MCI‐AD patients underwent neurological evaluation, neuropsychological assessment and lumbar puncture: in all these patients, the CSF profile, based on t‐tau, p‐tau, Aβ42 and Aβ42/40, was compatible with AD. OCT and OCT‐A have been used for evaluating retinal nerve fiber layer, ganglion cell layer and other retinal thicknesses and retinal and choroidal capillary plexuses. ANCOVA was used for comparing OCT measurements after adjustment for age, diabetes and hypertension. A significant reduction of superficial capillary plexus (10.10±0.81 vs. 10.79±0.67, p=0.012), deep capillary plexus (72.80±3.31 vs. 75.78±3.71, p=0.012) and intermediate capillary plexus (75.57±2.85 vs. 78.03±2.84, p=0.015) was found in MCI‐AD patients compared to controls. Conversely, the fractal dimension (FD) was increased in MCI‐AD with respect to control (1.51±0.02 vs. 1.50±0.01, p=0.044); CSF Abeta42/Tau ratio correlated negatively with FD (r=‐0.51, p=0.010). A reduction of retinal perfusion as opposed to an increased fractal dimension in MCI‐AD patients vs controls has been found. The latter finding could be due to a compensative mechanism. These data could support the role of OCT‐A as possible biomarker of prodromal AD. Further larger prospective studies are needed in order to confirm this hypothesis.