Retinal Arterio-Arterial Collaterals in Susac Syndrome

Background: The ophthalmic findings of Susac syndrome (SS) consist of visual field defects related to branch retinal artery occlusion (BRAO), and fluorescein angiography (FA) reveals a unique staining pattern. To date, retinal arterial collateral development has been described only in a single patient. Given that the immunopathological process in SS induces retinal ischemia, it is conceivable that abnormal blood vessel development may occur in affected individuals. Methods: This is a retrospective observational study. The medical records including fundus photography and FA of all patients with SS were reviewed, and those with any type of retinal arterial collateral were identified. Results: A total of 11 patients were identified with retinal collaterals. Five were men. Age ranged from 20 to 50 years. Ten patients had arterio-arterial (A-A) collaterals and 1 had arterio-venous (A-V) collaterals, and all had collaterals remote from the optic disc. No collaterals were present at onset of illness and the first developed at 9 months. Conclusions: The literature reveals scant evidence for the association between BRAO and retinal arterial collaterals. Our findings indicate that retinal arterial collaterals in SS are usually A-A and not A-V and may be more common in this disorder than previously believed. Collaterals do not develop early in the disease, and there may be a predilection toward development in men. The chronic inflammatory state of SS may be the stimulus for the development of these arterial collaterals.

Original Contribution Retinal Arterio-Arterial Collaterals in Susac Syndrome Robert A. Egan, MD, Guy Jirawuthiworavong, MD, Norah S. Lincoff, MD, John J. Chen, MD, PhD, Courtney E. Francis, MD, Jacqueline A. Leavitt, MD Background: The ophthalmic findings of Susac syndrome (SS) consist of visual field defects related to branch retinal artery occlusion (BRAO), and fluorescein angiography (FA) reveals a unique staining pattern. To date, retinal arterial collateral development has been described only in a single patient. Given that the immunopathological process in SS induces retinal ischemia, it is conceivable that abnormal blood vessel development may occur in affected individuals. Methods: This is a retrospective observational study. The medical records including fundus photography and FA of all patients with SS were reviewed, and those with any type of retinal arterial collateral were identified. Results: A total of 11 patients were identified with retinal collaterals. Five were men. Age ranged from 20 to 50 years. Ten patients had arterio-arterial (A-A) collaterals and 1 had arterio-venous (A-V) collaterals, and all had collaterals remote from the optic disc. No collaterals were present at onset of illness and the first developed at 9 months. Conclusions: The literature reveals scant evidence for the association between BRAO and retinal arterial collaterals. Our findings indicate that retinal arterial collaterals in SS are usually A-A and not A-V and may be more common in this disorder than previously believed. Collaterals do not develop early in the disease, and there may be a predilection toward development in men. The chronic inflammatory state of SS may be the stimulus for the development of these arterial collaterals. Journal of Neuro-Ophthalmology 2018;38:459-461 doi: 10.1097/WNO.0000000000000627 © 2018 by North American Neuro-Ophthalmology Society S usac syndrome (SS) classically presents with a clinical triad of vision loss, hearing loss, and encephalopathy and Department of Neurology and Ophthalmology (RAE), Rockwood Clinic, Spokane, Washington; Southern California Permanente Medical Group (GJ), Los Angeles, California; Department of Neurology and Ophthalmology (NSL), Jacobs School of Medicine, SUNY Buffalo, Buffalo, New York; Departments of Ophthalmology (JJC, JAL) and Neurology (JJC), Mayo Clinic, Rochester, Minnesota; and Department of Ophthalmology (CEF), University of Washington, Seattle, Washington. The authors report no conflicts of interest. Address correspondence to Robert A. Egan, MD, Department of Neurology, Rockwood Clinic, 910 W. 5th Avenue, Suite 1000, Spokane, WA 99204; E-mail: [e-mail] Egan et al: J Neuro-Ophthalmol 2018; 38: 459-461 a neuroimaging triad of white matter involvement, gray matter involvement, and leptomeningeal enhancement. Vision loss is caused by branch retinal artery occlusions (BRAOs) associated with Gass plaques, areas along arteriolar walls that may or may not be refractile and usually are located between, rather than at, arteriolar bifurcations (1,2). Henkind published a number of early reports describing retinal arterial collateral (3-5). Initially, he reviewed 22 cases of retinal arterial collaterals from the literature but did not categorize them as arterio-arterial (A-A) or arteriovenous (A-V). Subsequently, he determined that A-A collaterals were quite rare compared with A-V collaterals (4,5). We report a series of patients with SS who developed retinal A-A collaterals. METHODS Institutional review board approval was obtained for this study. The medical records including fundus photography and fluorescein angiography (FA) of patients with SS were reviewed retrospectively in this multicenter study. Patients were included only if they had initial and follow-up retinal imaging and developed collateral vessels. Age at onset of symptoms, sex, and time to onset of collateral development, if known, were recorded. RESULTS Twenty patients were included in the study and 11 had collaterals. All had suffered a previous BRAO. Five were men and age ranged from 20 to 50 years. Collaterals were A-A in 10 patients and arterior-venous in 1. No collaterals were present at onset of illness, and none were seen at 6 weeks. The shortest interval to development of collaterals was 9 months. Although visible on color fundus photography (Fig. 1), collaterals were easier to identify using FA (Fig. 2) and none were circumpapillary. 459 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. An arterio-arterial collateral (arrow) is present in the inferotemporal fundus of a 23-year-old woman. DISCUSSION There is little evidence in the literature for the association between retinal arterial collaterals and BRAO. Henkind (3) initially collected 22 previously published cases and, in 18 patients, ages ranged from 22 to 85 years (mean: 41 years). Two of the 4 subjects missing ages were listed as "young." Henkind stated that development of collaterals could occur within several weeks after BRAO but did not define if such collaterals were A-A or A-V or even neovascularization. Later, he reported A-A collaterals in a 31-year-old man with recurrent BRAOs (4). Sharma and Volpe (6) described a 33- FIG. 2. Fluorescein angiogram shows arterio-arterial collaterals (arrows) in a 26-year-old woman 9 months after initial presentation. 460 year-old man with bilateral BRAO and A-A collaterals. He had aortic valve disease and a calcific embolus in 1 fundus. The presumption was that the valve abnormality was the etiology of the bilateral retinal disease. There also are 4 reports of 5 patients with A-A collaterals located on the optic disc (Nettleship collaterals) after central retinal artery occlusion (CRAO) (7-10). A single report exists of similar collaterals on the optic disc after BRAO (11). Of importance, most, if not all, patients reported were young and often with bilateral BRAO. Although not confirmatory, the presence of bilateral BRAO in young adults is highly suggestive of SS. This disorder was not described until 1979 with the seminal publication by Susac et al (12). In 2008, Postelmans et al (13) reported a patient with SS in whom A-A collaterals were found 8 months after BRAO. In addition, there is a fundus photograph found in a review of diagnostic criteria for SS that reveals retinal collaterals (14). The sex and age of the patient were not given, and the type of collateral (AA vs A-V) cannot be determined from the photograph. Our findings indicate that retinal arterial collaterals in SS are most commonly A-A and not A-V. This observation coincides with the currently held pathophysiology that SS is primarily an arterial disease with antibodies causing endothelial damage (15). Collaterals do not develop early in the disease, and there may be a predilection toward development in men. We believe that the mechanism for the development of these A-A collaterals is a 2-step process. The first is the location of the occlusion that is peripheral. The second step is the chronic inflammatory state that allows capillary dilation to occur as a compensatory mechanism to reestablish blood flow. The inflammatory state seems to be an important factor otherwise we would witness A-A collateral development frequently after CRAO and BRAO. A limitation of our study is that it was not conducted prospectively. Also, it was not a common practice to photograph a patient late in the clinical course when disease activity is quiescent. In addition, there is a selection bias as patients with recurrent ocular events were typically photographed later, which suggest that these patients have more retinal than brain involvement with SS. Despite these limitations, the finding of retinal A-A collaterals away from the optic disc in a young patient with a previous BRAO should suggest the diagnosis of SS. Further research is required to determine how frequent this finding occurs in this syndrome. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: Robert A. Egan; b. Acquisition of data: Robert A. Egan, Guy Jirawuthiworavong, Norah S. Lincoff, John J. Chen, Courtney E. Francis, and Jacqueline A. Leavitt; c. Analysis and interpretation of data: Robert A. Egan, Guy Jirawuthiworavong, Norah S. Lincoff, John J. Chen, Courtney E. Francis, and Jacqueline A. Leavitt. Category 2: a. Drafting the manuscript: Robert A. Egan; b. Revising it for intellectual content: Robert A. Egan, Guy Jirawuthiworavong, Norah S. Lincoff, John J. Chen, Courtney E. Egan et al: J Neuro-Ophthalmol 2018; 38: 459-461 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Francis, and Jacqueline A. Leavitt. Category 3: a. Final approval of the completed manuscript: Robert A. Egan, Guy Jirawuthiworavong, Norah S. Lincoff, John J. Chen, Courtney E. Francis, and Jacqueline A. Leavitt. REFERENCES 1. Egan RA, Nguyen TH, Gass JDM, Rizzo JF, Tivnan J, Susac JO. 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