Optical coherence tomography identifies outer retina thinning in frontotemporal degeneration

Objective: Whereas Alzheimer disease (AD) is associated with inner retina thinning visualized by spectral-domain optical coherence tomography (SD-OCT), we sought to determine if the retina has a distinguishing biomarker for frontotemporal degeneration (FTD). Methods: Using a cross-sectional design, we examined retinal structure in 38 consecutively enrolled patients with FTD and 44 controls using a standard SD-OCT protocol. Retinal layers were segmented with the Iowa Reference Algorithm. Subgroups of highly predictive molecular pathology (tauopathy, TAR DNA-binding protein 43, unknown) were determined by clinical criteria, genetic markers, and a CSF biomarker (total tau: beta-amyloid) to exclude presumed AD. We excluded eyes with poor image quality or confounding diseases. SD-OCT measures of patients (n = 46 eyes) and controls (n = 69 eyes) were compared using a generalized linear model accounting for intereye correlation, and correlations between retinal layer thicknesses and Mini-Mental State Examination (MMSE) were evaluated. Results: Adjusting for age, sex, and race, patients with FTD had a thinner outer retina than controls (132 vs 142 mu m, p = 0.004). Patients with FTD also had a thinner outer nuclear layer (ONL) (88.5 vs 97.9 mu m, p = 0.003) and ellipsoid zone (EZ) (14.5 vs 15.1 mu m, p = 0.009) than controls, but had similar thicknesses for inner retinal layers. The outer retina thickness of patients correlated with MMSE (Spearman r = 0.44, p = 0.03). The highly predictive tauopathy subgroup (n = 31 eyes) also had a thinner ONL (88.7 vs 97.4 mm, p = 0.01) and EZ (14.4 vs 15.1 mm, p = 0.01) than controls. Conclusions: FTD is associated with outer retina thinning, and this thinning correlates with disease severity.