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C A S E
Ultra-Widefield Fluorescein Angiography Reveals Retinal Phlebitis in Susac’s Syndrome Michael A. Klufas, MD; Marc J. Dinkin, MD; Swetangi D. Bhaleeya, MD; Kristin O. Chapman, MD; Claire S. Riley, MD; Szilárd Kiss, MD ABSTRACT: A 23-year-old woman with history of headaches and auditory changes presented with acute-onset visual field loss in the right eye. The combination of multiple retinal branch artery occlusions of the right eye on funduscopic examination, characteristic white matter lesions in the corpus callosum on magnetic resonance imaging, and hearing loss on audiometric testing led to a diagnosis of Susac’s syndrome. Ultra-widefield fluorescein angiography revealed involvement of the retinal veins, which has not been previously reported with this condition. Additionally, ultrawidefield indocyanine green angiography demonstrated changes in the choroidal circulation, which are controversial in this syndrome. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:335-337.]
R E P O R T
■
INTRODUCTION
First described in 1979, Susac’s syndrome is an autoimmune endotheliopathy consisting of the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss.1 Funduscopic findings including retinal arterial wall plaques in idiopathic branch retinal artery occlusions now thought to be a form fruste of Susac’s syndrome were initially described by Gass.2 The largest study on the angiographic findings in Susac’s syndrome has shown segmental occlusions of the retinal arterioles without involvement of the retinal veins or choroidal circulation.3 We report novel fluorescein angiographic findings and the first ultrawidefield indocyanine green angiography in Susac’s syndrome. CASE REPORT
Clinical History
A 23- year-old woman with a 9-month history of migraines and episodes of left ear pain and auditory changes presented with acute-onset visual field loss of the right eye. Ophthalmologic Examination
Snellen acuity was 20/20 in both eyes. Pupils were equal, round, and reactive, without an afferent pupillary defect. Confrontation visual field testing revealed an inferior visual field defect in the right eye. Dilated fundus examination findings for the right eye were significant for multiple superior branch retinal artery occlusions with an associated area of retinal whitening. Dilated fundus examination findings for the left eye were unremarkable. Diagnostic Work-up
From the Weill Cornell Medical College, Department of Ophthalmology (MAK, MJD, SDB, KOC, SK), and Columbia University College of Physicians and Surgeons, Department of Neurology (CSR), New York, New York. Originally submitted August 18, 2013. Accepted for publication February 11, 2014. Posted online June 30, 2014. The authors have no financial or proprietary interest in the materials presented herein. Address correspondence to Szilárd Kiss, MD, Weill Cornell Medical College, New York-Presbyterian Hospital, 1305 York Avenue, 11th Floor, New York, NY 10021; 646-962-2217; email: [email protected]. doi: 10.3928/23258160-20140617-01
July/August 2014 · Vol. 45, No. 4
Systemic work-up was significant for a mildly elevated erythrocyte sedimentation rate (37 mm/hr), elevated cerebrospinal fluid protein (CSF; 70 mg/dL) without oligoclonal bands or pleocytosis, and magnetic resonance imaging (MRI) of the brain that demonstrated multiple linear or rounded T2 hyperintense lesions throughout the corpus callosum that did not extend outside its borders and bilateral periventricular corona radiata T2 lesions (Figure 2, page 337). Audiometric testing results were normal in the right ear and showed low-frequency neurosensory hearing loss in the left. A complete hypercoaguable, infectious, and uveitis assessment was unrevealing.
335
Figure 1. Fundus photograph of right eye with area of superior retinal whitening and segmentation of arterial blood column with Kyrieleis plaques in superior arteries (A, inset) and normal-appearing left eye (B). (C) Fluorescein angiography of right eye with multiple superior branch retinal artery occlusions, arterial wall hyperfluoresence, and temporal venous wall hyperfluoresence (inset left) as well as luminal venous staining (inset right). (D) Fluorescein angiography of left eye showing inferonasal branch retinal artery occlusion with venous wall hyperfluoresence nasally and temporally (inset). (E) Indocyanine green angiography of right eye showing filling defect (inset left) and leakage of larger choroidal vessels (inset right). (F) Indocyanine green angiography of left eye with patchy areas of hypofluoresence (inset left) that persisted into later frames (inset right).
Multiple branch retinal artery occlusions combined with hearing loss, new-onset migraines, snowball corpus callosal lesions on MRI, and elevated CSF protein led to the diagnosis of Susac’s syndrome. The patient was treated with intravenous and oral steroids, intravenous immunoglobulin, mycophenolate mofetil, and aspirin. Ultra-widefield fundus photography (UWF-FP; Figures 1A-B), fluorescein angiography (UWF-FA; Figures 1C-D), and indocyanine green angiography (UWF-ICGA; Figures 1E-F) were performed. UWFFP in the right eye showed a superior wedge area of retinal whitening with Kyrieleis plaques4 (described by Gass as “yellow-white periarterial plaques or sheathing,”2 and later renamed by Egan et al as retinal arterial wall plaques5 and Gass plaques6) in retinal arterioles (Figure 1A, inset). UWF-FP of the left eye revealed no abnormality (Figure 1B). UWF-FA in the right eye showed multiple areas of delayed filling
superiorly and arterial wall hyperfluoresence.6 There was venous wall hyperfluoresence and moderate intraluminal hyperfluoresence within the veins (Figure 1C, inset) temporally not in association with the arterial findings in the right eye. UWF-FA in the left eye showed a nasal branch retinal artery occlusion not observed on ophthalmoscopy or UWF-FP. Venous wall hyperfluoresence was noted in the left eye (Figure 1D, inset). UWF-ICGA in the right eye revealed multiple filling defects within choroidal vessels, persisting into the late phase, and leakage from choroidal vessels (Figure 1E, inset). UWF-ICGA in the left eye uncovered multiple round areas of hypofluoresence that persisted into the late phase (Figure 1F, inset).
336
Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina
DISCUSSION
This is the first case report to describe changes in the retinal venous circulation in Susac’s syndrome and the first to characterize these findings using UWF-
Figure 2. Sagittal (A) and axial (B) fluid-attenuated inversion recovery magnetic resonance imaging sequences of the brain showing multiple lesions of corpus callosum (arrows).
FA and UWF-ICGA. With multimodality UWF imaging, we observed that vascular changes in Susac’s syndrome are not exclusively confined to the retinal arteries.3 On UWF-FA in our patient, changes in the retinal veins were apparent in both eyes. The peripheral location of the venous changes on UWF-FA may explain why this finding has not been observed previously using standard-field FA. These changes are consistent with a histopathologic report of an eye with Susac’s syndrome that showed a ribbon-like appearance of a vein with serous luminal deposits.7 A brain biopsy in Susac’s syndrome has shown venule endothelial cell necrosis.8 To the best of our knowledge, in vivo angiographic changes in retinal veins have not been previously reported in Susac’s syndrome. On UWF-ICGA, both eyes exhibited findings consistent with the autoimmune endotheliopathy underlying Susac’s syndrome. The one previous report of ICGA in a patient with Susac’s syndrome also indicated likely involvement of the choroidal circulation,9 although UWF imaging was not used. In our patient, Susac’s syndrome involved not only the retinal arteries but also the retinal veins and choroidal vasculature. UWF-FA and UWF-ICGA may
July/August 2014 · Vol. 45, No. 4
be an important tool in the diagnosis and monitoring of response to treatment in patients with Susac’s syndrome.
REFERENCES 1. Rennebohm R, Susac JO, Egan RA, Daroff RB. Susac’s Syndrome-update. J Neurol Sci. 2010;299(1-2):86-91. 2. Johnson MW, Flynn HW, Jr., Gass JD. Idiopathic recurrent branch retinal arterial occlusion. Arch Ophthalmol. 1989;107(5):757. 3. Martinet N, Fardeau C, Adam R, et al. Fluorescein and indocyanine green angiographies in Susac syndrome. Retina. 2007;27(9):12381242. 4. Kyrieleis W. Uber atypische gerfaesstuberkulose der netzhaut. Arch Augenheilkd. 1933;107:182-190. 5. Egan RA, Ha Nguyen T, Gass JD, et al. Retinal arterial wall plaques in Susac syndrome. Am J Ophthalmol. 2003;135(4):483-486. 6. Egan RA, Hills WL, Susac JO. Gass plaques and fluorescein leakage in Susac Syndrome. J Neurol Sci. 2010;299(1-2):97-100. 7. McLeod DS, Ying HS, McLeod CA, et al. Retinal and optic nerve head pathology in Susac’s syndrome. Ophthalmology. 2010;118(3):548552. 8. Magro CM, Poe JC, Lubow M, Susac JO. Susac syndrome: an organspecific autoimmune endotheliopathy syndrome associated with antiendothelial cell antibodies. Am J Clin Pathol. 2010;136(6):903-912. 9. Balaskas K, Guex-Crosier Y, Borruat FX. Indocyanine-green angiography findings in Susac’s syndrome. Klin Monbl Augenheilkd. 2012; 229(4):426-427.
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C A S E
Ultra-Widefield Fluorescein Angiography Reveals Retinal Phlebitis in Susac’s Syndrome Michael A. Klufas, MD; Marc J. Dinkin, MD; Swetangi D. Bhaleeya, MD; Kristin O. Chapman, MD; Claire S. Riley, MD; Szilárd Kiss, MD ABSTRACT: A 23-year-old woman with history of headaches and auditory changes presented with acute-onset visual field loss in the right eye. The combination of multiple retinal branch artery occlusions of the right eye on funduscopic examination, characteristic white matter lesions in the corpus callosum on magnetic resonance imaging, and hearing loss on audiometric testing led to a diagnosis of Susac’s syndrome. Ultra-widefield fluorescein angiography revealed involvement of the retinal veins, which has not been previously reported with this condition. Additionally, ultrawidefield indocyanine green angiography demonstrated changes in the choroidal circulation, which are controversial in this syndrome. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:335-337.]
R E P O R T
■
INTRODUCTION
First described in 1979, Susac’s syndrome is an autoimmune endotheliopathy consisting of the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss.1 Funduscopic findings including retinal arterial wall plaques in idiopathic branch retinal artery occlusions now thought to be a form fruste of Susac’s syndrome were initially described by Gass.2 The largest study on the angiographic findings in Susac’s syndrome has shown segmental occlusions of the retinal arterioles without involvement of the retinal veins or choroidal circulation.3 We report novel fluorescein angiographic findings and the first ultrawidefield indocyanine green angiography in Susac’s syndrome. CASE REPORT
Clinical History
A 23- year-old woman with a 9-month history of migraines and episodes of left ear pain and auditory changes presented with acute-onset visual field loss of the right eye. Ophthalmologic Examination
Snellen acuity was 20/20 in both eyes. Pupils were equal, round, and reactive, without an afferent pupillary defect. Confrontation visual field testing revealed an inferior visual field defect in the right eye. Dilated fundus examination findings for the right eye were significant for multiple superior branch retinal artery occlusions with an associated area of retinal whitening. Dilated fundus examination findings for the left eye were unremarkable. Diagnostic Work-up
From the Weill Cornell Medical College, Department of Ophthalmology (MAK, MJD, SDB, KOC, SK), and Columbia University College of Physicians and Surgeons, Department of Neurology (CSR), New York, New York. Originally submitted August 18, 2013. Accepted for publication February 11, 2014. Posted online June 30, 2014. The authors have no financial or proprietary interest in the materials presented herein. Address correspondence to Szilárd Kiss, MD, Weill Cornell Medical College, New York-Presbyterian Hospital, 1305 York Avenue, 11th Floor, New York, NY 10021; 646-962-2217; email: [email protected]. doi: 10.3928/23258160-20140617-01
July/August 2014 · Vol. 45, No. 4
Systemic work-up was significant for a mildly elevated erythrocyte sedimentation rate (37 mm/hr), elevated cerebrospinal fluid protein (CSF; 70 mg/dL) without oligoclonal bands or pleocytosis, and magnetic resonance imaging (MRI) of the brain that demonstrated multiple linear or rounded T2 hyperintense lesions throughout the corpus callosum that did not extend outside its borders and bilateral periventricular corona radiata T2 lesions (Figure 2, page 337). Audiometric testing results were normal in the right ear and showed low-frequency neurosensory hearing loss in the left. A complete hypercoaguable, infectious, and uveitis assessment was unrevealing.
335
Figure 1. Fundus photograph of right eye with area of superior retinal whitening and segmentation of arterial blood column with Kyrieleis plaques in superior arteries (A, inset) and normal-appearing left eye (B). (C) Fluorescein angiography of right eye with multiple superior branch retinal artery occlusions, arterial wall hyperfluoresence, and temporal venous wall hyperfluoresence (inset left) as well as luminal venous staining (inset right). (D) Fluorescein angiography of left eye showing inferonasal branch retinal artery occlusion with venous wall hyperfluoresence nasally and temporally (inset). (E) Indocyanine green angiography of right eye showing filling defect (inset left) and leakage of larger choroidal vessels (inset right). (F) Indocyanine green angiography of left eye with patchy areas of hypofluoresence (inset left) that persisted into later frames (inset right).
Multiple branch retinal artery occlusions combined with hearing loss, new-onset migraines, snowball corpus callosal lesions on MRI, and elevated CSF protein led to the diagnosis of Susac’s syndrome. The patient was treated with intravenous and oral steroids, intravenous immunoglobulin, mycophenolate mofetil, and aspirin. Ultra-widefield fundus photography (UWF-FP; Figures 1A-B), fluorescein angiography (UWF-FA; Figures 1C-D), and indocyanine green angiography (UWF-ICGA; Figures 1E-F) were performed. UWFFP in the right eye showed a superior wedge area of retinal whitening with Kyrieleis plaques4 (described by Gass as “yellow-white periarterial plaques or sheathing,”2 and later renamed by Egan et al as retinal arterial wall plaques5 and Gass plaques6) in retinal arterioles (Figure 1A, inset). UWF-FP of the left eye revealed no abnormality (Figure 1B). UWF-FA in the right eye showed multiple areas of delayed filling
superiorly and arterial wall hyperfluoresence.6 There was venous wall hyperfluoresence and moderate intraluminal hyperfluoresence within the veins (Figure 1C, inset) temporally not in association with the arterial findings in the right eye. UWF-FA in the left eye showed a nasal branch retinal artery occlusion not observed on ophthalmoscopy or UWF-FP. Venous wall hyperfluoresence was noted in the left eye (Figure 1D, inset). UWF-ICGA in the right eye revealed multiple filling defects within choroidal vessels, persisting into the late phase, and leakage from choroidal vessels (Figure 1E, inset). UWF-ICGA in the left eye uncovered multiple round areas of hypofluoresence that persisted into the late phase (Figure 1F, inset).
336
Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina
DISCUSSION
This is the first case report to describe changes in the retinal venous circulation in Susac’s syndrome and the first to characterize these findings using UWF-
Figure 2. Sagittal (A) and axial (B) fluid-attenuated inversion recovery magnetic resonance imaging sequences of the brain showing multiple lesions of corpus callosum (arrows).
FA and UWF-ICGA. With multimodality UWF imaging, we observed that vascular changes in Susac’s syndrome are not exclusively confined to the retinal arteries.3 On UWF-FA in our patient, changes in the retinal veins were apparent in both eyes. The peripheral location of the venous changes on UWF-FA may explain why this finding has not been observed previously using standard-field FA. These changes are consistent with a histopathologic report of an eye with Susac’s syndrome that showed a ribbon-like appearance of a vein with serous luminal deposits.7 A brain biopsy in Susac’s syndrome has shown venule endothelial cell necrosis.8 To the best of our knowledge, in vivo angiographic changes in retinal veins have not been previously reported in Susac’s syndrome. On UWF-ICGA, both eyes exhibited findings consistent with the autoimmune endotheliopathy underlying Susac’s syndrome. The one previous report of ICGA in a patient with Susac’s syndrome also indicated likely involvement of the choroidal circulation,9 although UWF imaging was not used. In our patient, Susac’s syndrome involved not only the retinal arteries but also the retinal veins and choroidal vasculature. UWF-FA and UWF-ICGA may
July/August 2014 · Vol. 45, No. 4
be an important tool in the diagnosis and monitoring of response to treatment in patients with Susac’s syndrome.
REFERENCES 1. Rennebohm R, Susac JO, Egan RA, Daroff RB. Susac’s Syndrome-update. J Neurol Sci. 2010;299(1-2):86-91. 2. Johnson MW, Flynn HW, Jr., Gass JD. Idiopathic recurrent branch retinal arterial occlusion. Arch Ophthalmol. 1989;107(5):757. 3. Martinet N, Fardeau C, Adam R, et al. Fluorescein and indocyanine green angiographies in Susac syndrome. Retina. 2007;27(9):12381242. 4. Kyrieleis W. Uber atypische gerfaesstuberkulose der netzhaut. Arch Augenheilkd. 1933;107:182-190. 5. Egan RA, Ha Nguyen T, Gass JD, et al. Retinal arterial wall plaques in Susac syndrome. Am J Ophthalmol. 2003;135(4):483-486. 6. Egan RA, Hills WL, Susac JO. Gass plaques and fluorescein leakage in Susac Syndrome. J Neurol Sci. 2010;299(1-2):97-100. 7. McLeod DS, Ying HS, McLeod CA, et al. Retinal and optic nerve head pathology in Susac’s syndrome. Ophthalmology. 2010;118(3):548552. 8. Magro CM, Poe JC, Lubow M, Susac JO. Susac syndrome: an organspecific autoimmune endotheliopathy syndrome associated with antiendothelial cell antibodies. Am J Clin Pathol. 2010;136(6):903-912. 9. Balaskas K, Guex-Crosier Y, Borruat FX. Indocyanine-green angiography findings in Susac’s syndrome. Klin Monbl Augenheilkd. 2012; 229(4):426-427.
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