Functional and structural retinal alterations in Alzheimer’s disease: insights from photopic negative response (PhNR) and OCT-based analysis

Abstract

Background: We evaluated retinal function and structure in Alzheimer’s disease (AD) using photopic negative response (PhNR) from full-field electroretinography (ERG) and using optical coherence tomography (OCT)-based retinal layer measurements. Methods: Ninety eyes from 61 subjects (31 controls, 30 AD patients) were included. Full-field ERGs were recorded using chromatic red-on-blue stimulation (1.7 cd·s/m2 flashes over an 8 cd/m2 blue background) in accordance with the ISCEV extended PhNR protocol. The AD group included 16 females and 14 males with moderate cognitive impairment (mean MMSE 15.5 ± 3.9). ERG a-wave, b-wave, and PhNR amplitudes were recorded. Macular and peripapillary retinal nerve fiber layer (RNFL) thicknesses were measured by OCT. Results: A-wave (AD: − 13.4 ± 11.9 µV, control: − 32.5 ± 13.7 µV, p < 0.001), b-wave (AD: 59.1 ± 28 µV, control: 156 ± 48.8 µV, p < 0.001), PhNR (AD: − 21.4 ± 14.9 µV, control: − 51 ± 15.4 µV, p < 0.001) amplitudes were lower in AD. Thicknesses of the central INL (AD: 25 ± 6.6 µm, control: 25.2 ± 8.2 µm, p = 0.04), inferior OPL (AD: 32.7 ± 6.2 µm, control: 36.9 ± 8.9 µm, p = 0.01), and temporal OPL (AD: 29.3 ± 5.2 µm, control: 34.8 ± 7.0 µm, p = 0.001) were reduced in AD, while other retinal layers showed no significant differences between groups (p > 0.05). The b-wave amplitude showed the highest discriminative power with an AUC of 0.956, followed by the PhNR amplitude (AUC = 0.930) and the a-wave amplitude (AUC = 0.904). Conclusion: AD was associated with a generalized reduction in full-field ERG amplitudes, accompanied by selective retinal layer changes on OCT. Among electrophysiological measures, b-wave amplitude demonstrated the highest ability to distinguish AD patients from controls.