Retinal nerve fiber layer in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

Abstract

Purpose: Tauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect in vivo. This study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate in vivo the difference in peripapillary retinal nerve fibre layer (pRNFL) thickness and macular retinal thickness between participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP-43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia).

Study design: Prospective, multi-centre, observational study.

Materials and methods: pRNFL and macular SD-OCT images were acquired in both eyes of each participant using Heidelberg Spectralis SD-OCT. Global and pRNFL thickness in 6 sectors were analyzed, as well as macular thickness in a central 1 mm diameter zone and 4 surrounding sectors. Linear mixed model methods adjusting for baseline differences between groups were used to compare the two groups with respect to pRNFL and macular thickness.

Results: A significant difference was found in mean pRNFL thickness between groups, with the TDP-43 group (n = 28 eyes) having a significantly thinner pRNFL in the temporal sector than the tauopathy group (n = 9 eyes; mean difference = 15.46 μm, SE = 6.98, p = 0.046), which was not significant after adjusting for multiple comparisons. No other significant differences were found between groups for pRNFL or macular thickness.

Conclusion: The finding that the temporal pRNFL in the TDP-43 group was on average 15.46 μm thinner could potentially have clinical significance. Future work with larger sample sizes, longitudinal studies, and at the level of retinal sublayers will help to determine the utility of SD-OCT to differentiate between these two proteinopathies.

Keywords: TDP-43 proteinopathy; amyotrophic lateral sclerosis; frontotemporal lobar degeneration; optical coherence tomography; retinal nerve fibre layer; tauopathy.

FIGURE 1

Macular grid with 1, 3, and 6 mm diameter circles centered on the foveola (left). Measurements for average thickness (black) in areas of each sector of the macula (right). Only the central five macular sectors were analyzed in this study: central macula, and the inner superior, inferior, nasal, and temporal sectors, bordered by the 3 mm diameter circle.

FIGURE 2

Mean (SE) difference (tauopathy – TDP43, μm) in average (A) macular sectoral thickness and (B) pRNFL sectoral and global thickness. The difference in pRNFL thickness between groups in the temporal sector (p < 0.05; medium effect size of 0.61) is illustrated in bold. This difference was not significant after adjusting for multiple comparisons. Note that average thickness in the macular scan is within the area of each sector and represents total retinal thickness, while in the pRNFL scan it is along the circular line of each sector and represents RNFL thickness only. T, Temporal; N, Nasal.