Longitudinal Assessment Using Optical Coherence Tomography in Patients with Friedreich's Ataxia

Abstract

Ocular abnormalities occur frequently in Friedreich's ataxia (FRDA), although visual symptoms are not always reported. We evaluated a cohort of patients with FRDA to characterise the clinical phenotype and optic nerve findings as detected with optical coherence tomography (OCT). A total of 48 patients from 42 unrelated families were recruited. Mean age at onset was 13.8 years (range 4-40), mean disease duration 19.5 years (range 5-43), mean disease severity as quantified with the Scale for the Assessment and Rating of Ataxia 22/40 (range 4.5-38). All patients displayed variable ataxia and two-thirds had ocular abnormalities. Statistically significant thinning of average retinal nerve fibre layer (RNFL) and thinning in all but the temporal quadrant compared to controls was demonstrated on OCT. Significant RNFL and macular thinning was documented over time in 20 individuals. Disease severity and visual acuity were correlated with RNFL and macular thickness, but no association was found with disease duration. Our results highlight that FDRA is associated with subclinical optic neuropathy. This is the largest longitudinal study of OCT findings in FRDA to date, demonstrating progressive RNFL thickness decline, suggesting that RNFL thickness as measured by OCT has the potential to become a quantifiable biomarker for the evaluation of disease progression in FRDA.

Keywords: FRDA; Friedreich’s ataxia; OCT; RNFL; optical coherence tomography; retinal nerve fibre layer.

Figure 1

Retinal fundus images with circular volume scan delineation of FRDA patients with varying degrees of optic neuropathy. (a) Normal appearance of the optic disc (patient 33); (b) Optic disc pallor in a patient with normal visual acuity (patient 2); (c) Diffuse optic disc pallor in a patient with reduced visual acuity (patient 21). N Nasal; T Temporal.

Figure 2

Retinal nerve fibre layer thickness of patients with FRDA. This figure demonstrates reduced sectorial superior quadrant thickness in patients 42 (a) and 5 (b), and reduced temporal and inferior quadrant thickness in patient 45 (c). Pie graphs of quadrants (T = temporal; S = superior; N = nasal; I = inferior) and RNFL circular tomogram representing quantitative analysis of RNFL thickness (black line) and normative data set (green area = 95% confidence interval, yellow area = 99% CI, red area = outside 99% CI).

Figure 3

Retinal thickness and SARA score over time. (a) Average RNFL thickness at baseline and at follow-up evaluation; (b) Macular thickness at baseline and at follow-up evaluation; (c) Foveal thickness at baseline and at follow-up evaluation; (d) SARA score at baseline and at follow-up assessment.

Figure 3

Retinal thickness and SARA score over time. (a) Average RNFL thickness at baseline and at follow-up evaluation; (b) Macular thickness at baseline and at follow-up evaluation; (c) Foveal thickness at baseline and at follow-up evaluation; (d) SARA score at baseline and at follow-up assessment.