Angioarchitectural alterations in the retina and choroid in frontotemporal dementia

Abstract

Objective: Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder that affects the frontal and temporal lobes of the brain, leading to cognitive decline and personality changes. The objective of this cross-sectional study was to characterize angioarchitectural changes in the retina and choroid of individuals with FTD compared to cognitively normal controls using optical coherence tomography (OCT) and OCT angiography (OCTA).

Methods: Cross-sectional comparison of patients with FTD and controls with normal cognition. All participants underwent Mini-Mental State Examination (MMSE) at the time of imaging. Outcome measures included OCT parameters: retinal nerve fiber layer (RNFL) thickness, ganglion cell layer-inner plexiform layer (GC-IPL) thickness, central subfield thickness (CST), subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI); and OCTA superficial capillary plexus parameters: foveal avascular zone (FAZ) area, 3x3mm and 6x6mm macular perfusion density (PD) and vessel density (VD), 4.5x4.5mm peripapillary capillary perfusion density (CPD) and capillary flux index (CFI). Generalized estimating equation analysis was used to account for the inclusion of 2 eyes from the same participant.

Results: 29 eyes of 19 patients with FTD and 85 eyes of 48 controls were analyzed. In FTD, 3x3mm macular PD (p = 0.02) and VD (p = 0.02) and CFI (p = 0.01) were reduced compared to controls. There was no difference in average 4.5x4.5mm CPD, RNFL thickness, GC-IPL thickness, CST, SFCT, CVI, FAZ, or 6x6mm VD or PD between FTD and controls (all p > 0.05); however, there was a trend toward lower macular 6x6mm PD and VD in patients with FTD.

Conclusion: Decline of peripapillary and macular OCT and OCTA parameters merit further investigation as potential biomarkers for FTD detection. Noninvasive retinal and choroidal imaging may hold promise for earlier detection, and future longitudinal studies will clarify their role in monitoring of FTD.

Fig 1. Representative ganglion cell analysis of the macula.

Ganglion cell analysis (Carl Zeiss Meditec, Dublin, CA) of the macula of the left eye in an individual with frontotemporal dementia (FTD) (A) and the left eye of a control with normal cognition (B) with corresponding ganglion cell-inner plexiform layer thickness for the elliptical annular region of the FTD participant (C) and the control participant (D). I = inferior; IN = inferonasal; IT = inferotemporal; S = superior; SN = superonasal; ST = superotemporal.

Fig 2. Representative 3x3-mm macular OCT angiography.

3x3-mm macular OCT angiography (OCTA) images of the superficial capillary plexus (SCP) of the left eye of an individual with frontotemporal dementia (FTD) (A) and the left eye of a control with normal cognition (B). Corresponding quantitative color maps of (C-D) perfusion density and (E-F) vessel density of the SCP, with the scale on the right. Zeiss Cirrus HD-5000 Spectral-Domain OCT with AngioPlex OCTA software, version 11.0.0.29946 (Carl Zeiss Meditec).

Fig 3. Representative 4.5x4.5-mm peripapillary OCT angiography.

4.5x4.5-mm peripapillary OCT angiography (OCTA) images of the radial peripapillary capillary (RPC) plexus of the left eye of an individual with frontotemporal dementia (FTD) with average peripapillary capillary flux index (CFI) 0.441 (A) and the left eye of a control with normal cognition with average CFI 0.467 (B). Zeiss Cirrus HD-5000 Spectral-Domain OCT with AngioPlex OCTA software, version 11.0.0.29946 (Carl Zeiss Meditec).