Neuro-Ophthalmological Findings in Friedreich's Ataxia

Abstract

Friedreich ataxia (FRDA) is a progressive neurodegenerative disease caused by a severe autosomal recessive genetic disorder of the central nervous (CNS) and peripheral nervous system (PNS), affecting children and young adults. Its onset is before 25 years of age, with mean ages of onset and death between 11 and 38 years, respectively. The incidence is 1 in 30,000-50,000 persons. It is caused, in 97% of cases, by a homozygous guanine-adenine-adenine (GAA) trinucleotide mutation in the first intron of the frataxin (FXN) gene on chromosome 9 (9q13-q1.1). The mutation of this gene causes a deficiency of frataxin, which induces an altered inflow of iron into the mitochondria, increasing the nervous system's vulnerability to oxidative stress. The main clinical signs include spinocerebellar ataxia with sensory loss and disappearance of deep tendon reflexes, cerebellar dysarthria, cardiomyopathy, and scoliosis. Diabetes, hearing loss, and pes cavus may also occur, and although most patients with FRDA do not present with symptomatic visual impairment, 73% present with clinical neuro-ophthalmological alterations such as optic atrophy and altered eye movement, among others. This review provides a brief overview of the main aspects of FRDA and then focuses on the ocular involvement of this pathology and the possible use of retinal biomarkers.

Keywords: FRDA; Friedreich ataxia; eye; neurodegeneration; neurological disability; retina.

Figure 1

Neuro-ophthalmological findings in FRDA. FRDA: Friedreich’s ataxia, OCT: optical coherence tomography, pRNFL: peripapillary retinal nerve fiber layer, GCC: ganglion cell complex, VOR: vestibulo-ocular reflexes, CS: contrast sensitivity, BCVA: best-corrected visual acuity, VF: visual field, VEP: visual evoked potential. Images modified from https://smart.servier.com/ (accessed on 21 July 2021).

Figure 2

OCT and FRDA: summarize the sequential involvement. In the early onset of FRDA, there is an affectation of pRNFL; in the intermediate FRDA, there is a loss in the ganglion cell complex (GCC); and in advanced stages, there is a thinning in the macular area.

Figure 3

Flow chart materials and methods. Abbreviations: ALS: Amyotrophic lateral sclerosis; FRDA: Friedreich’s ataxia.