CIRCUMSCRIBED OUTER FOVEOLAR DEFECTS IN SPINOCEREBELLAR ATAXIA TYPE 7 William M. Watkins, MD,* Scott D. Schoenberger, MD,* Patrick Lavin, MD,*† Anita Agarwal, MD*

Purpose: To report circumscribed outer foveolar defects in a 40-year-old man with a history of spinocerebellar ataxia type 7. Methods: A 40-year-old man with genetically confirmed spinocerebellar ataxia type 7 presented with progressive vision loss and decreased color perception for 3 years. He underwent a full ocular examination, fundus photography, autofluorescence, spectraldomain optical coherence tomography imaging, and a full-field electroretinogram. Results: The patient’s ocular examination and fundus autofluorescence were both normal except for mild temporal pallor of both optic discs. Spectral-domain optical coherence tomographic imaging showed foveal thinning with an outer foveolar defect because of focal loss of photoreceptors, disruption of the inner segment–outer segment junction but preservation of the external limiting membrane, and thinning of the outer plexiform layer in both eyes. Electroretinography showed severely reduced cone function with mildly reduced rod function. Conclusion: Spinocerebellar ataxia type 7 should be included in the differential diagnosis for “outer retinal holes” or “foveal cavitation,” which also includes solar retinopathy, juxtafoveal telangiectasia, Welder maculopathy, tamoxifen retinopathy, Stargardt disease, amyl nitrate abuse, and cone or cone–rod degeneration syndromes. RETINAL CASES & BRIEF REPORTS 7:294–296, 2013

a rare neurodegenerative condition that typically has retinal findings most resembling a cone or cone–rod degeneration.

From the *Vanderbilt Eye Institute, Nashville, Tennessee; and †Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee.

A

loss of foveal photoreceptor reflectivity on optical coherence tomography (OCT) was termed “outer retinal hole” and “foveal cavitation” by various authors.1,2 This OCT finding is described in many ophthalmic conditions, such as solar retinopathy, juxtafoveal telangiectasia, Welder maculopathy, tamoxifen retinopathy, Stargardt disease, and amyl nitrate abuse.1 Recently, Leng et al2 described similar OCT findings in several patients with nonspecific “cone dysfunction syndromes.” The following case illustrates similar findings in spinocerebellar ataxia type 7 (SCA-7),

Case Report A 40-year-old man presented with progressive vision loss and decreased color perception for 3 years. His medical history was notable for progressive cerebellar ataxia for 8 years with genetic testing confirmed SCA-7. He had 2 children with SCA-7 who died at 3 and 8 years of age. His mother is living with mild ataxia and visual loss. His visual acuity was 20/60 in the right eye and 20/50 in the left eye, with decreased color vision in both eyes. The anterior segment examination was normal. Funduscopic examination (Figure 1, A and B) was unremarkable except for mild temporal pallor of both optic discs. No macular or foveal changes were discerned even on fundus autofluorescence imaging (Figure 1, C and D). Spectral-domain OCT revealed foveal thinning with an outer foveolar defect because of focal loss of photoreceptors. Disruption of the inner segment–outer segment junction was present, but the external limiting membrane was preserved (Figure 1, E and F). In addition, the outer plexiform layer in the nasal macula was thinner compared with the temporal macula. Spectral-domain OCT of the optic disc and peripapillary retinal nerve fiber layer revealed bilateral peripapillary retinal nerve fiber layer

Supported in part by an unrestricted grant from Research to Prevent Blindness to the Vanderbilt University School of Medicine Department of Ophthalmology and Visual Sciences. None of the authors have any financial conflicts of interest. Reprint requests: Anita Agarwal, MD, Vanderbilt Eye Institute, 2311 Pierce Avenue, Nashville, TN 37232; e-mail: anita.agarwal@ vanderbilt.edu

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OUTER FOVEOLAR DEFECT IN SCA-7

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Fig. 1. Fundus photography and spectral-domain optical coherence tomographic findings of the patient. Funduscopy (A and B) was unremarkable except for temporal optic disc pallor in both eyes. No macular or foveal changes were seen. Fundus autofluorescence of the right eye (C) and left eye (D) was normal. Spectral-domain optical coherence tomography of the right eye (E) and left eye (F) displayed foveal thinning with a focal loss of foveolar photoreceptors, disruption of the inner segment–outer segment junction, and preservation of the external limiting membrane. In addition, the outer plexiform layer in the nasal macula was thinner compared with the temporal macula.

thinning most prominent temporally (not shown). A full-field electroretinogram revealed severely reduced cone responses and mildly reduced rod responses (Table 1).

Discussion Spinocerebellar ataxia type 7 is a rare neurodegenerative disease characterized by gait and limb ataxia,

dysarthria, slow saccades, ophthalmoplegia, and dysphagia.3 SCA-7 is inherited in an autosomal dominant fashion with anticipation, whereby future generations are more severely affected than preceding generations, and is usually more severe with paternal transmission as illustrated in our patient’s family history. Sporadic cases occur rarely.4 CAG trinucleotide repeats occur in the coding region of a gene on

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RETINAL CASES & BRIEF REPORTS´  2013  VOLUME 7  NUMBER 3 Table 1. Electroretinographic Findings of the Patient and Age-matched Controls

Electroretinographic Stimulus −24 dB Scotopic b-wave 0 dB Scotopic a-wave 0 dB Scotopic b-wave 0 dB Photopic b-wave 30 Hz Photopic flicker

Amplitude Range of Age-matched Controls (mV)

Right Eye Amplitude (mV)

Left Eye Amplitude (mV)

141.35–342.65 163–443 386.95–773.05 81.95–204.05 55.5–154.5

124 48 199 19 24

152 97 246 14 31

chromosome 3p12-13, resulting in a defective ataxin-7 protein.3 Downstream effects of a defective ataxin-7 protein include abnormal expression of rhodopsin and the cone opsins. In one review of SCA-7, 3 of 10 patients reported visual symptoms before ataxia.5 The only type of spinocerebellar ataxia that is nearly always associated with retinal degeneration is SCA-7, and the findings are consistent with a cone or cone–rod degeneration. Ocular symptoms include decreased visual acuity, dyschromatopsia, peripheral visual field loss, and nyctalopia.5 Cone dysfunction seems to be the first manifestation followed by rod dysfunction. Funduscopic examination may be normal early in the disease, even with substantial vision loss and an abnormal electroretinogram, and later progresses to retinal pigment epithelial changes and bull’s eye maculopathy. The OCT changes may be the only abnormal finding when the fundus is still normal as seen in our case. So far, the most frequently reported finding on OCT is diffuse foveal thinning.3,6,7 With progression of the disease, thinning may spread to the entire macula. Circumscribed outer retinal defects with focal loss of photoreceptors resembling solar maculopathy has been seen previously in a case with time-domain OCT.8 Spectral-domain OCT in our patient showed a similar foveolar defect. Peripapillary retinal nerve fiber layer thinning, as can be seen with other types of cone–rod dystrophy,9 was present, suggesting either transneuronal degeneration or that both photoreceptors and retinal ganglion cells were targeted by the pathogenic process; the latter is more likely as neuronal involvement can be widespread and include cerebellar Purkinje neurons, upper motor neurons, ocular motor and other brainstem neurons, and even peripheral nerves on occasion.10 Spinocerebellar ataxia type 7 should be included in the differential diagnosis of foveal cavitation or outer retinal holes, particularly with reports of sporadic cases of SCA-7 and in those with anticipation where a family history may be lacking. A neurologic review

of systems may sometimes be normal as ocular symptoms can predate neurologic manifestations. As a result, SCA-7 may present initially as an isolated ocular condition mimicking one of the nonneurodegenerative conditions listed above. Given the severe implications for the offspring of affected individuals, early diagnosis is helpful to patients and their families. Key words: circumscribed outer foveolar defect, cone dystrophy, foveal cavitation, outer retinal hole, spinocerebellar ataxia type 7. References 1. Comander J, Gardiner M, Lowenstein J. High-resolution optical coherence tomography findings in solar maculopathy and the differential diagnosis of outer retinal holes. Am J Ophthalmol 2011;152:413–419. 2. Leng T, Marmor MF, Kellner U, et al. Foveal cavitation as an optical coherence tomography finding in central cone dysfunction. Retina 2012;32:1411–1419. 3. Manrique RK, Noval S, Aguilar-Amat MJ, et al. Ophthalmic features of spinocerebellar ataxia type 7. J Neuroophthalmol 2009;29:174–179. 4. Mittal U, Roy S, Jain S, et al. Post-zygotic de novo trinucleotide repeat expansion at spinocerebellar ataxia type 7 locus: evidence from an Indian family. J Hum Genet 2005;50:155–157. 5. Miller RC, Tewari A, Miller JA, et al. Neuro-ophthalmologic features of spinocerebellar ataxia type 7. J Neuroophthalmol 2009;29:180–186. 6. Kumar N, Pulido JS. High-definition spectral domain optical coherence tomography in the evaluation of ataxia with visual impairment. Br J Ophthalmol 2011;95:591, 598. 7. Ahn JK, Seo JM, Chung H, Yu HG. Anatomical and functional characteristics in atrophic maculopathy associated with spinocerebellar ataxia type 7. Am J Ophthalmol 2005;139:923–925. 8. Aleman TS, Cideciyan AV, Volpe NJ, et al. Spinocerebellar ataxia type 7 (SCA7) shows a cone-rod dystrophy phenotype. Exp Eye Res 2002;74:737–745. 9. Pasadhika S, Fishman GA, Allikmets R, Stone EM. Peripapillary retinal nerve fiber layer thinning in patients with autosomal recessive cone-rod dystrophy. Am J Ophthalmol 2009;148:260–265. 10. Seidel K, Siswanto S, Brunt ER, et al. Brain pathology of spinocerebellar ataxias. Acta Neuropathol 2012;124:1–21.

Circumscribed outer foveolar defects in spinocerebellar ataxia type 7.

To report circumscribed outer foveolar defects in a 40-year-old man with a history of spinocerebellar ataxia type 7...
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