Functionally Relevant Maculopathy and Optic Atrophy in Spinocerebellar Ataxia Type 1

Abstract

Background Spinocerebellar ataxia type 1 (SCA‐ATXN1) is an inherited progressive ataxia disorder characterized by an adult‐onset cerebellar syndrome combined with nonataxia signs. Retinal or optic nerve affection are not systematically described. Objectives To describe a retinal phenotype and its functional relevance in SCA‐ATXN1. Methods We applied optical coherence tomography (OCT) in 20 index cases with SCA‐ATXN1 and 22 healthy controls (HCs), investigating qualitative changes and quantifying the peripapillary retinal nerve fiber layer (pRNFL) thickness and combined ganglion cell and inner plexiform layer (GCIP) volume as markers of optic atrophy and outer retinal layers as markers of maculopathy. Visual function was assessed by high‐ (HC‐VA) and low‐contrast visual acuity (LC‐VA) and the Hardy‐Rand‐Rittler pseudoisochromatic test for color vision. Results Five patients (25%) showed distinct maculopathies in the ellipsoid zone (EZ). Furthermore, pRNFL ( P < 0.001) and GCIP ( P = 0.002) were reduced in patients (pRNFL, 80.86 ± 9.49 μm; GCIP, 1.84 ± 0.16 mm 3 ) compared with HCs (pRNFL, 97.02 ± 8.34 μm; GCIP, 1.98 ± 0.12 mm 3 ). Outer macular layers were similar between groups, but reduced in patients with maculopathies. HC‐VA ( P = 0.002) and LC‐VA ( P < 0.001) were reduced in patients (HC‐VA [logMAR]: 0.01 ± 010; LC‐VA [logMAR]: 0.44 ± 0.16) compared with HCs (HC‐VA [logMAR]: –0.12 ± 0.08; LC‐VA [logMAR]: 0.25 ± 0.05). Color vision was abnormal in 2 patients with maculopathies. Conclusions A distinct maculopathy, termed EZ disruption, as well as optic atrophy add to the known nonataxia features in SCA‐ATXN1. Whereas optic atrophy may be understood as part of a widespread neurodegeneration, EZ disruption may be explained by effects of ataxin‐1 gene or protein on photoreceptors. Our findings extend the spectrum of nonataxia signs in SCA‐ATXN1 with potential relevance for diagnosis and monitoring.

OCT parameters of the optic nerve head and the retina as surrogate markers of brain volume in a normal population, a pilot study

“…The suggested correlation of the cerebellum volume and the GCL-IPL complex thickness may be related to the structural similarities in both areas, that includes spatial organizations, and molecular expressions of regulatory factors, although our findings did not reach statistical significance [81,82]. The association of retinal dysfunction to cerebellar ataxias is well documented [83][84][85][86][87]. The nature of the exact mechanism for the retinal involvement in the ataxias may be multifactorial, based on the exact pathophysiology of each entity, but an underling parallel relationship of the two structures is likely part of the explanation and the present correlation.…”

Macular Morpho-Functional and Visual Pathways Functional Assessment in Patients with Spinocerebellar Type 1 Ataxia with or without Neurological Signs

“…Previous studies performed in visually impaired SCA-AXN1 patients [12,13], reported macular dysfunction assessed by mfERG recording [10,12], as well as macular morphological abnormalities detected by Sd-OCT examination. About the RGCs function, in absence of PERG results in SCA-ATXN1 patients, it seems that this matter was never investigated in this disease; regarding the RGC axon morphology, contrasting evidence has been reported, describing either reduced [13,17] or normal RNFL-T values [15].…”

“…In the overt SCA1 disease, as in other ADSCAs [6][7][8], relevant ocular impairment inducing a decrease in visual function has been reported. In details, macular dystrophy, outer retinal cavitation or foveal photoreceptoral disruption [9][10][11][12][13][14], as well as eye movement abnormalities or visual pathways disorders, as optic atrophy [13,[15][16][17], have been described in patients with neurological signs (SP).…”

Ophthalmic Manifestations and Genetics of the Polyglutamine Autosomal Dominant Spinocerebellar Ataxias: A Review

“…They also asserted that OCT and multifocal ERG could help to reliably detect these macular pathology associated with SCA1 ( Nishiguchi et al, 2019 ). Color vision abnormalities may present in some SCA1 patients with photoreceptor ellipsoid zone disruption ( Oertel et al, 2020 ).…”

“…A recent case series by Nishiguchi et al reported temporal RNFL thinning ( Nishiguchi et al, 2019 ). Oertel et al has reported that peripapillary retinal nerve fiber layer thickness and combined ganglion cell and inner plexiform layer volume as markers of optic atrophy measured by OCT were reduced in 20 patients with SCA1 compared with healthy controls ( Oertel et al, 2020 ).…”