Inner and outer retinal abnormalities detected in Alzheimer's disease subjects diagnosed by amyloid PET not revealed when classified based on clinical criteria.

BACKGROUND

Previous studies on retinal changes in Alzheimer's disease (AD) using optical coherence tomography (OCT) and electroretinography (ERG) based on clinical diagnostic criteria have yielded inconsistent results. We evaluated retinal structure and function in subjects classified using clinical and biological definitions.

METHODS

Fifty-nine included subjects underwent comprehensive neuropsychiatric and ophthalmic evaluations, including OCT and ERG with photopic negative response (PhNR). Amyloid status was determined by 11C-Pittsburgh compound B positron emission tomography (PET).

RESULTS

No significant differences in evaluated OCT and ERG parameters were found between cognitively impaired and unimpaired groups. Amyloid-positive subjects showed significantly thinner macular, inner plexiform, and inner nuclear layers, plus ERG abnormalities (reduced PhNR, smaller waves amplitudes, prolonged a-wave latency) (p < 0.05). ERG outperformed OCT in discriminating amyloid status (area under the curve [AUC] = 0.84). Standardized uptake value ratio (SUVr) correlated with Mini-Mental State Examination (MMSE; r = 0.62, p < 0.05).

DISCUSSION: Biomarker-based classification revealed retinal changes, affecting both inner retina and photoreceptors, not detected using clinical criteria.

HIGHLIGHTS: Retinal studies in Alzheimer's disease yield mixed results when based on clinical criteria.Amyloid positron emission tomography classification permits recognition of retinal changes missed clinically.Optical coherence tomography (OCT) shows early macular thinning in amyloid beta positive subjects at the expense of inner layers.Electroretinography detects outer retinal dysfunction, indicating broader involvement.Retinal function loss on electroretinography precedes inner/outer changes on OCT.