Persistent and Progressive Outer Retina Thinning in Frontotemporal Degeneration.

Benjamin J Kim,Tomas S Aleman,Sophia Dominguez-Perez,Joshua L Dunaief,Samantha Saludades,Gui-Shuang Ying,David J Irwin,Wei Pan,Delu Song,Murray Grossman

doi:10.3389/fnins.2019.00298

Abstract

ObjectiveWhile 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.MethodsSD-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 (n = 16 patients, 30 eyes) and the tauopathy subgroup (n = 9 patients,16 eyes) were compared to controls (n = 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.ResultsCompared to controls, returning FTD patients (143 vs. 130 μm, p = 0.005) and the tauopathy subgroup (143 vs. 128 μm, p = 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 (p = 0.34), but was significant for the tauopathy subgroup (−3.9 vs. 0.4 μm/year, p = 0.03). Outer retina thickness change correlated with MMSE change in FTD patients (Spearman rho = 0.60, p = 0.02) and the tauopathy subgroup (rho = 0.73, p = 0.04).ConclusionOur 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.

Highlights

Frontotemporal degeneration (FTD) syndromes can have clinical presentations that overlap with Alzheimer’s Disease (AD) (Irwin et al, 2015)
As expected from the baseline demographics, compared to controls, the FTD patients had a similar percentage of male participants but had a greater mean age and a higher percentage of Caucasian race (Table 1)
When evaluating only the probable tauopathy subgroup compared to controls, we found a significant rate of thinning of the outer retina (p = 0.04) and a significant rate of thickening of the outer plexiform layer (OPL) (p = 0.02) in univariate analysis (Table 7)

Summary

Introduction

Frontotemporal degeneration (FTD) syndromes can have clinical presentations that overlap with Alzheimer’s Disease (AD) (Irwin et al, 2015). In a cross-sectional study of FTD patients predominantly composed of probable tauopathy patients, we found that FTD is associated with outer retina (photoreceptor layer) thinning compared to normal controls (Kim et al, 2017). This contrasts with numerous reports of SD-OCT detected inner retina (nerve fiber and ganglion cell layer) thinning associated with AD and confirmed with histopathology (Hinton et al, 1986; Cheung et al, 2015; Coppola et al, 2015; Garcia-Martin et al, 2016; Chan et al, 2018). Amyotrophic lateral sclerosis, which has clinical-pathological overlap with FTLDTDP, is associated with inner retina thinning (Irwin et al, 2015; Volpe et al, 2015)

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