Longitudinal Changes in the Macula and Optic Nerve in Familial Dysautonomia

Abstract

Purpose : Familial Dysautonomia (FD) is an incurable hereditary sensory and autonomic neuropathy with significant visual impairment and general morbidity. In this study we characterize the longitudinal changes in the macula, peripapillary and the optic nerve head (ONH) in subjects with FD.

Methods : Data was consecutively collected from subjects attending the NYU FD clinic between 2012-2019. All subjects were imaged with spectral-domain OCT (Cirrus HD-OCT; Zeiss, Dublin, CA) using optic disc cube 200x200 and macular cube 512X128 scans. Global and sectoral measurements of mean retinal nerve fiber layer (RNFL) and macular ganglion cell and inner plexiform layer (GCIPL) thicknesses, and ONH parameters of rim area, average cup-to-disc (C:D) ratio, and cup volume were used for the analysis. The best fit models (linear, quadratic and broken stick linear model) were used to describe the longitudinal change in each of the parameters.

Results : 91 subjects (149 eyes) with FD of ages 5-56 years were included in the analysis. A broken stick model was the best fitted model for the rate of change of global RNFL and GCIPL thicknesses with a statistically significant rate of decline before the tipping point [-0.861 µm/year (95% CI: -1.026, -0.693) and -0.553 µm/year (95% CI: -0.645, -0.461), respectively] and a non-significant slope after the tipping point. This tipping point (or floor effect) was reached at the age of 24.8 for RNFL and 26.1 for GCIPL. Out of the four RNFL quadrants, subjects reached the temporal tipping point at the youngest age (Figure 1). The best fitted model for all ONH parameters was the linear model with a statistically significant rate of progression (Figure 2). A subset of subjects (24%) had no cupping and did not show progression in any of the ONH parameters but demonstrated a significant rate of decline in RNFL and GCIPL.

Conclusions : The rapidly declining RNFL and GCIPL can explain the progressive visual impairment previously reported in these subjects. Among all structural parameters, ONH parameters might be suitable for a longer follow-up period, in eyes with a measurable cup. Future studies evaluating the association between ocular and systemic disease status are needed.

This is a 2020 ARVO Annual Meeting abstract.

 

Figure 1. RNFL rate of change per year. The red marks represent the age at the tipping point of each quadrant.

 

Figure 2. Cup Volume rate of change per year. A subset of patients presenting no cupping (pink square).