Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer's disease

PURPOSE: To determine alterations in the retina of patients with Alzheimer's disease (AD) by the newly developed technique of fluorescence lifetime imaging ophthalmoscopy (FLIO) in a pilot study. METHODS: FLIO set-up uses a scanning laser ophthalmoscope (HRA2, Heidelberg Engineering, Germany), which was modified by the use of an excitation pulse laser BLD440 (Becker&Hickl, Berlin, Germany) and detection of fluorescence lifetime by time-correlated single photon counting (TCSPC; Becker&Hickl) in two spectral channels (channel 1: 490-560 nm, channel 2: 560-700 nm). Least square fit of three exponential functions was used for fluorescence decay analysis. That resulted in three fluorescent components with lifetimes τi , amplitudes αi and relative contributions Qi . 16 patients with AD (mean age 77.2 ± 7.0 years) were investigated. After regular ophthalmic investigation, FLIO examination and OCT examination were performed. Alzheimer-specific clinical data were collected (MMSE, cerebrospinal fluid (CSF) concentration of amyloid-β (1-42), total-tau and phosphorylated tau181 (p-tau181) protein). RESULTS: The FLIO parameters of the second fluorescent component α2 and Q2 (channel 2) correlated significantly with MMSE score (Q2 , R = -0.757, p = 0.007; α2 , R = -0.618, p = 0.043) as well as p-tau181-protein concentration in CSF (Q2 , R = 0.919, p = 0.009; α2 , R = 0.881, p = 0.020) in patients with AD. OCT measurements of retinal nerve fibre layer thickness, optic disc excavation and macular thickness neither correlated with Alzheimer-specific CSF data nor MMSE score. CONCLUSIONS: Unlike conventional techniques, such as OCT, the new technique of FLIO revealed changes in the retina of patients with AD in relation to Alzheimer-specific markers in this pilot study.