Persistent and Progressive Outer Retina Thinning in Frontotemporal Degeneration

While Alzheimer's disease is associated with inner retina thinning measured by spectral-domain optical coherence tomography (SD-OCT), our previous cross-sectional study suggested outer retina thinning in frontotemporal degeneration (FTD) patients compared to controls without neurodegenerative disease; we sought to evaluate longitudinal changes of this potential biomarker. SD-OCT retinal layer thicknesses were measured at baseline and after 1-2 years. Clinical criteria, genetic analysis, and a cerebrospinal fluid biomarker (total tau: β-amyloid) to exclude likely underlying Alzheimer's disease pathology were used to define a subgroup of predicted molecular pathology (i.e., tauopathy). Retinal layer thicknesses and rates of change in all FTD patients ( = 16 patients, 30 eyes) and the tauopathy subgroup ( = 9 patients,16 eyes) were compared to controls ( = 30 controls, 47 eyes) using a generalized linear model accounting for inter-eye correlation and adjusting for age, sex, and race. Correlations between retinal layer thicknesses and Mini-Mental State Examinations (MMSE) were assessed. Compared to controls, returning FTD patients (143 vs. 130 μm, = 0.005) and the tauopathy subgroup (143 vs. 128 μm, = 0.03) had thinner outer retinas but similar inner layer thicknesses. Compared to controls, the outer retina thinning rate was not significant for all FTD patients ( = 0.34), but was significant for the tauopathy subgroup (-3.9 vs. 0.4 μm/year, = 0.03). Outer retina thickness change correlated with MMSE change in FTD patients (Spearman rho = 0.60, = 0.02) and the tauopathy subgroup (rho = 0.73, = 0.04). Our finding of FTD outer retina thinning persists and longitudinally correlates with disease progression. These findings were especially seen in probable tauopathy patients, which showed progressive outer retina thinning.