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

Bryan M Wong; Christopher Hudson; Emily Snook; Faryan Tayyari; Hyejung Jung; Malcolm A Binns; Saba Samet; Richard W Cheng; Carmen Balian; Efrem D Mandelcorn; Edward Margolin; Elizabeth Finger; Sandra E Black; David F Tang-Wai; Lorne Zinman; Brian Tan; Wendy Lou; Mario Masellis; Agessandro Abrahao; Andrew Frank; Derek Beaton; Kelly M Sunderland; Stephen R Arnott; ONDRI Investigators; Maria Carmela Tartaglia; Wendy V Hatch

doi:10.3389/fnins.2022.964715

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

Front Neurosci. 2022 Oct 6:16:964715. doi: 10.3389/fnins.2022.964715. eCollection 2022.

Authors

Bryan M Wong^{1

2}, Christopher Hudson^{2

3}, Emily Snook¹, Faryan Tayyari^{3

4}, Hyejung Jung⁵, Malcolm A Binns^{5

6}, Saba Samet², Richard W Cheng⁴, Carmen Balian^{3

4}, Efrem D Mandelcorn^{2

4}, Edward Margolin^{2

4}, Elizabeth Finger⁷, Sandra E Black^{8

9}, David F Tang-Wai^{9

10}, Lorne Zinman^{8

9}, Brian Tan⁶, Wendy Lou⁵, Mario Masellis^{8

9}, Agessandro Abrahao^{8

9}, Andrew Frank¹¹, Derek Beaton⁶, Kelly M Sunderland⁶, Stephen R Arnott⁶; ONDRI Investigators; Maria Carmela Tartaglia^{9

10}, Wendy V Hatch^{2

4}

Collaborators

ONDRI Investigators:
Sabrina Adamo, Stephen Arnott, Rob Bartha, Derek Beaton, Courtney Berezuk, Alanna Black, Alisia Bonnick, David Breen, Don Brien, Susan Bronskill, Dennis Bulman, Leanne Casaubon, Ying Chen, Marvin Chum, Brian Coe, Ben Cornish, Jane Lawrence Dewar, Roger A Dixon, Sherif El-Defrawy, Sali Mk Farhan, Frederico Faria, Julia Fraser, Mahdi Ghani, Barry Greenberg, Hassan Haddad, Wendy Hatch, Melissa Holmes, Chris Hudson, Peter Kleinstiver, Donna Kwan, Elena Leontieva, Brian Levine, Wendy Lou, Efrem D Mandelcorn, Ed Margolin, Connie Marras, Bill McIlroy, Paula McLaughlin, Manuel Montero Odasso, Doug Munoz, David Munoz, Nuwan Nanayakkara, J B Orange, Miracle Ozzoude, Alicia Peltsch, Pradeep Raamana, Joel Ramirez, Natalie Rashkovan, Angela Roberts, Yanina Sarquis Adamson, Christopher Scott, Michael Strong, Stephen Strothers, Sujeevini Sujanthan, Kelly M Sunderland, Sean Symons, Faryan Tayyari, Athena Theyers, Angela Troyer, Abiramy Uthirakumaran, Karen Van Ooteghem, John Woulfe, Mojdeh Zamyadi, Guangyong Gy Zou

Affiliations

¹ Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
² Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada.
³ School of Optometry and Vision Science, University of Waterloo, Waterloo, ON, Canada.
⁴ Kensington Eye Institute, Toronto, ON, Canada.
⁵ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁶ Rotman Research Institute, Baycrest Health Sciences, Toronto, ON, Canada.
⁷ Department of Clinical Neurological Sciences, Western University, London, ON, Canada.
⁸ Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
⁹ Department of Medicine, Division of Neurology, University of Toronto, Toronto, ON, Canada.
¹⁰ Krembil Brain Institute, University Health Network Memory Clinic, Toronto, ON, Canada.
¹¹ Bruyere Research Institute, University of Ottawa, Ottawa, ON, Canada.

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.

Copyright © 2022 Wong, Hudson, Snook, Tayyari, Jung, Binns, Samet, Cheng, Balian, Mandelcorn, Margolin, Finger, Black, Tang-Wai, Zinman, Tan, Lou, Masellis, Abrahao, Frank, Beaton, Sunderland, Arnott, ONDRI Investigators, Tartaglia and Hatch.