Multimodal Retinal Imaging in Spinocerebellar Ataxia Type 1 Maculopathy

INTRODUCTION

Spinocerebellar ataxias (SCAs) are a heterogeneous group of dominantly inherited disorders involving the degeneration of the cerebellum, and often the brainstem, basal forebrain, and spinal cord.^[1] SCA type 1 (SCA1) is an autosomal dominant condition that involves the expansion of a cytosine-adenine-guanine (CAG) repeat sequence on chromosome 6. The elongated CAG repeat results in an expanded polyglutamine tract which produces the gene ataxin-1, a protein which aggregates in the brains of patients affected by SCA1.^[2] Typical disease onset occurs during early adulthood with multisystemic involvement occurring in the early stages of the disease.^[3] Neurological signs and symptoms include gait ataxia and dysarthria. Ocular findings are often present and include hypermetric saccades, nystagmus, and the development of upgaze palsy.^[2] Optic neuropathy and macular dysfunction leading to vision loss have previously been reported in association with the condition.^[3] The previous studies have highlighted abnormal observations in optical coherence tomography (OCT) imaging and electroretinography (ERG).^[4-6] Although the hallmark symptoms of the disease have been well catalogued, documentation of the ophthalmic imaging findings related to the associated maculopathy in the literature is limited. This case report presents the multimodal ocular imaging including swept-source OCT, en-face OCT, OCT angiography, and fundus autofluorescence in a patient presenting with SCA1 maculopathy.

CASE DESCRIPTION

A 70-year-old man with genetically confirmed SCA1 was referred to ophthalmology for progressive bilateral visual loss. On examination, he was found to have hypermetric saccades jerky eye pursuit movements, with horizontal nystagmus on lateral gaze bilaterally. The patient did not report diplopia or visual distortion although he did note a reduction in color vision, with a corresponding score of 4 on the Ishihara 10 plate test bilaterally. The patient had previous bilateral cataract surgery, with clear posterior chamber intraocular lenses visible on slit-lamp examination. His pupil examination and intraocular pressure were within normal limits bilaterally. His best-corrected visual acuity was 20/80 OD and 20/100 OS at the time of consultation. On dilated fundus examination, normal discs and vessels were visualized, alongside previously lasered senile retinoschisis and a blunted macular reflex. Although scotopic and photopic full-field ERG responses were within normal limits, multifocal ERG revealed bilateral central macular cone dysfunction, localized to the central <10° radius of both retinas. Fundus photography (Optos California, Optos PLC Edinburgh, U.K) depicted bilateral hypopigmentation of the fovea OU [Figure 1a] and prior laser scars in the inferotemporal periphery OD. Green autofluorescence (Optos California, Optos PLC Edinburgh, U.K) revealed a blunting of the macular hypo-autofluorescence signal in the macula OU, with hypoautofluorescence at the location of the laser scars OD [Figure 1b]. Swept-source OCT (Topcon Triton, Tokyo, Japan) of the macula demonstrated attenuation of the external limiting membrane and ellipsoid zone in the subfoveal region [Figure 2]. Swept-source en-face OCT (Topcon Triton, Tokyo, Japan) with segmentation at the level of the ellipsoid zone revealed an oval region of attenuated signal consistent with the transverse OCT findings of photoreceptor loss [Figure 3]. Swept-source OCT angiography (Topcon Triton, Tokyo, Japan) of the superficial capillary plexus, deep capillary plexus, and choriocapillaris exhibited no abnormalities.

Close

Figure 1:: (a and b) Pseudocolor fundus photographs and (c and d) green fundus autofluorescence of the right and left eyes, respectively. Pseudocolor photographs depict hypopigmentation of the fovea OU and prior laser scars in the inferotemporal periphery OD. Green autofluorescence images illustrate a blunting of the macular hypo-autofluorescence signal in the macula OU with hypoautofluorescence at the location of the laser scars OD. The optic nerve head and retinal vessels appear appropriate bilaterally.

Export to PPT

Close

Figure 2:: (a and b) Swept-source optical coherence tomography (OCT) B-scans of the right and left macula, respectively, obtained using Topcon Triton™. OCT demonstrated notable attenuation of the external limiting membrane and ellipsoid zone in the subfoveal region, as indicated by the arrows.

Export to PPT

Close

Figure 3:: (a and b) Swept-source en-face optical coherence tomography scans of the ellipsoid zone in the right and left eyes taken using Topcon Triton™. The images, with segmentation at the level of the ellipsoid zone, demonstrate attenuated signal consistent with central photoreceptor loss as indicated by the arrows.

Export to PPT

DISCUSSION

SCA1 is a rare autosomal dominant condition that may be associated with both neurological and ophthalmological signs.^[3] As a nucleotide repeat disorder, pathogenesis of SCA1 involves the mutation of the 6p22.3 gene which leads to abnormal protein translation, resulting in aberrant protein interactions and allele instability. The disease phenotype and age of onset show marked variability, reflective of differences in repeat size between individuals.^[1]

Confirmed SCA1 has been associated with progressive visual disturbance, retinal degeneration, and optic atrophy.^[3,6] However, studies investigating maculopathy in association with SCA1 are especially limited due to the small number of patients presenting with this development. Multiple previous studies have assessed various visual functions through a variety of imaging modalities [Table 1]. To the best of our knowledge, this is the first study to present comprehensive multimodal imaging in one with confirmed SCA1 and maculopathy.

Cone dystrophies comprise a group of disorders characterized by abnormal cone system visual field thresholds and cone-mediated mfERGs, with full-field rod-mediated ethylene response factor amplitudes ranging from 50% reduction to normal functioning.^[7] A subset of patients may present with involvement of only the central cones, with normal full-field ERG recordings.^[7] Inherited cone dystrophies have been reported in association with autosomal recessive, autosomal dominant, and X-linked recessive inheritance, with some manifestations limited to purely a cone origin and others later indicating rod dysfunction.^[8] Cone dystrophies that may involve secondary rod dystrophy have been reported in association with neurofibromatosis type 1, Bardet-Biedl syndrome, Alström syndrome, Pierre Marie ataxia, SCA7, amelogenesis imperfecta, and trichomegaly.^[8] Cone dystrophies have been associated with the involvement of several chromosomal loci and genes, not limited to COD2, RCD1 and 2, GUCA1A, RPGR, CNGA3, and CNGB3.^[8] Of these, the two progressive manifestations involving symptoms consistent with cerebellar ataxia, such as those in our patient, are SCA and Pierre Marie ataxia,^[4,9] with genetic testing identifying SCA1 as the culprit in this case.

Primarily affecting cone system function, progressive cone dystrophy involves reduced visual acuity, photophobia, and abnormal color vision, often in the presence of a normal fundus examination.^[10] Patients with SCA-1 have been found to have a loss of cones, with bilateral foveal cavities or central retinal thinning.^[6,11,12] Multimodal ocular retinal imaging was performed to evaluate our patient’s maculopathy [Figure 4]. OCT angiography images did not exhibit any vascular abnormalities and his fundus photography was notable for bilateral hypopigmentation of the fovea. It is important to note that the blunted autofluorescence signal detected bilaterally may be associated with retinal pigment epithelial (RPE) degeneration. Swept-source OCT, coupled with en-face imaging, revealed an attenuation of the ellipsoid zone consistent with photoreceptor loss. The thinning of the ellipsoid region and the RPE degeneration may jointly account for the patient’s otherwise unexplained loss of visual acuity bilaterally.

Close

Figure 4:: Swept-source optical coherence tomography (Topcon Triton, Tokyo Japan) nerve fiber layer (NFL) and ganglion cell layer (GCL) analysis of the right eye (a) demonstrating nerve fiber layer thinning and early GCL loss and (b) the left eye revealing a normal NFL measurement with mild GCL loss.

Export to PPT

The results of the scotopic and photopic full-field ERG were within normal limits and were not indicative of a rod-cone dystrophy. However, abnormalities of the multifocal ERG may indicate an early cone dysfunction affecting the macular region, with similar results noted in another patient with SCA-1 maculopathy.^[3] In a previously reported SCA1 case series involving heterogeneous intrafamilial expression, subtle and overt maculopathy were found in the presence and absence of ocular symptoms and were attributed to pigmentary macular dystrophy secondary to rod and cone dysfunction.^[3,4,13] This finding, coupled with our multimodal imaging results, suggests that assessment of SCA1 patients with macular imaging may be appropriate before the onset of visual symptoms or at the time of initial diagnosis. Specifically, the use of OCT and en-face OCT is the most useful measures in assessing photoreceptor changes and may be used to monitor progressive macular dystrophy.

CONCLUSION

Patients with SCA-1 maculopathy may present with progressive loss of visual acuity and abnormal color vision, with correlated findings on mfERG. OCT and en-face OCT are useful tools to visualize and assess SCA-1 maculopathy findings and should be considered as part of the routine examination in these patients.