A pilot study of fluorescence lifetime imaging ophthalmoscopy in preclinical Alzheimer’s disease

To investigate fluorescence lifetime imaging ophthalmoscopy (FLIO) findings in preclinical Alzheimer’s disease (AD). This prospective, observational study enrolled patients with early AD undergoing Alzheimer’s biomarker analysis and matched controls. Alzheimer-associated parameters (β-amyloid [Aβ], total tau in cerebrospinal fluid [CSF], Mini-Mental Status Examination [MMSE], etc.), risk factor-associated data (body mass index [BMI], hypertension, lipid profile, etc.), ganglion cell layer plus inner plexiform layer (GCIPL) thickness in structural optical coherence tomography (OCT), OCT angiography data, and FLIO-derived parameters (τm, τ1, τ2, and τ3) in short and long spectral channels (SSC and LSC) were compared and correlated between the two groups. Additional analyses were performed separately within subgroups of phakic and pseudophakic. A total of 28 eyes from 15 subjects (8 control and 7 AD) were included in this analysis. In FLIO parameters, τm in AD group showed longer lifetimes compared to the controls in phakic subjects (593.9 ± 93.3, 454.4 ± 38.6 ps; 475.0 ± 71.6, 394.1 ± 28.2  ps in SSC and LSC of AD and control groups, respectively, p = 0.036 and 0.024). Aβ, tau in CSF, and GCIPL thickness correlated with τm in the LSC for phakic subjects (r = −0.611 to 0.562, p < 0.05 for all), but only the GCIPL thickness showed a correlation with FLIO parameters in pseudophakic subjects (r = −0.893 to −0.795, p < 0.001 for all). FLIO-derived parameters appear to correlate with Aβ, tau levels in the CSF, and GCIPL thickness on OCT in AD patients. If these findings can be validated in future longitudinal studies, FLIO may prove to be useful as a simple, non-invasive diagnostic tool for AD.