The New Zealand Genetic Frontotemporal Dementia Study (FTDGeNZ): Baseline retinal characteristics

Purpose : Frontotemporal dementia (FTD) is a leading cause of early-onset dementia. It is crucial to identify individuals who are in the pre-symptomatic stages of FTD, particularly with the advent of therapeutic agents for neurodegenerative disorders. Previous reports have detailed retinal layer thinning in patients with sporadic FTD, and pre-symptomatic individuals with FTD caused by progranulin mutations. The New Zealand Genetic FTD Study (FTDGeNZ) is a prospective, longitudinal study that aims to identify pre-clinical biomarkers of FTD, including retinal markers, in a large New Zealand family cohort with an autosomal dominant tau mutation that is known to cause FTD (MAPT IVS 10+16 C>T).

Methods : All participants (carriers and non-carriers) completed a comprehensive neuro-ophthalmic examination, including fundus auto-fluorescence, spectral domain optical coherence tomography (OCT) of the peripapillary retinal nerve fibre layer (RNFL) and macula, and OCT angiography (OCT-A) of the superficial retinal vessels, with the examiner masked to the gene status of participants. One eye of each participant was included in between-group analysis and age-matched paired analysis (1:1 ratio).

Results : Twenty-five members of the family cohort enrolled in the study, including 6 carriers of the genetic mutation (mean age 41.2 ± 12.0 years), and 19 non-carriers (41.3 ± 14.3 years). The two groups had similar baseline ocular and refractive characteristics. There was no statistically significant difference (p > 0.05) between carriers and non-carriers for average RNFL thickness (100.2 ± 8.1 µm vs. 94.6 ± 6.1 µm), average ganglion cell complex thickness (85.6 ± 2.8 µm vs. 82.9 ± 5.6 µm), macular vessel density (18.13 ± 0.52 mm/mm2 vs. 18.02 ± 0.89 mm/mm2) or macular perfusion (44.75 ± 1.07% vs. 44.11 ± 1.88%). Additionally, after accounting for multiple comparisons, there were no significant differences in peripapillary or macular sector results for both OCT and OCT-A. These findings were consistent across age-matched paired analysis.

Conclusions : This is the first study to report OCT and OCT-A findings in a pre-symptomatic cohort with a tau mutation. No significant differences were identified in OCT or OCT-A measurements between carriers and non-carriers at baseline. Longitudinal, within-subject analysis of this cohort will determine the role of OCT/OCT-A assessment as a potential biomarker of pre-symptomatic FTD.