Indocyanine-Green Angiography Findings in Susac’s Syndrome

Susac’s syndrome was first identified in 1979 as a specific entity consisting of the clinical triad of encephalopathy, branch retinal arterial occlusions and hearing loss [1]. Women are more commonly affected than men (3:1) and the age of onset peaks at 21 – 41 years but ranges widely (16 – 58 years). The natural history of the condition is variable with spontaneous resolution in some patients or profound cognitive and hearing impairment in others. However, severe visual dysfunction is exceptional. Susac’s syndrome is thought to result from an auto-immune mechanism, and this hypothesis is supported both by the results of histopathology studies, and in view of the favourable effects of immuno-suppresive treatment. However, the exact aetiology and mechanisms leading to Susac’s syndrome are currently unknown [2]. Diagnosis is suspected from the clinical presentation and supported by the results of paraclinical examinations. Cerebral magnetic resonance imaging (MRI) can reveal the presence of multiple hyperintense cerebral lesions, especially involving the corpus callosum [3].

The presence of retinal vascular alterations is mandatory for the diagnosis of Susac`s disease. The role of fluorescein angiography (FA) is essential for both the diagnosis and management of Susac’s syndrome. Hyper-fluorescence of the retinal arteriolar walls can be found both proximally to the site of occlusion but also in areas remote from the occluded arterioles. FA may play a role in monitoring subclinical disease activity, contributing to treatment optimisation [4]. Choroidal circulation, on the other hand, is thought to be preserved in Susac’s syndrome, as ICGA did not reveal any alterations in a series of 7 patients [5]. We report a case of Susac’s syndrome in whom ICGA disclosed choroidal lesions. To the best of our knowledge this is the first report of choroidal lesions in Susac’s syndrome.

A 30 year-old female patient was referred to the Jules Gonin Eye Hospital for retinal evaluation in the setting of a cerebral vasculitis in September 2006. The patient had a ten-day history of severe tension headaches, often pulsatile and worse upon awakening, associated with nausea and vomiting. Complaints were mainly of an unsteady gait, intermittent paraesthesias of the face and lower extremities, emotional instability and forgetfulness. She also reported unformed visual hallucinations (flashing lights) with both eyes. Neurological examination revealed an ataxic gait and global cognitive dysfunction with memory loss. MRI disclosed peri-ventricular white matter lesions, hyperintense on T2 and FLAIR sequences, particularly involving the corpus callosum and the posterior fossa. There were no signs of intracranial hypertension or meningism. Audiometric evaluation revealed bilateral, asymmetric neurosensory hearing loss more pronounced for lower frequencies. Extensive investigations were unrevealing for viral or bacterial infection, systemic vasculitis or multiple sclerosis.

Ophthalmologic evaluation revealed normal visual acuity (20/20 OU), colour vision (13/13 Ishihara plates OU) and computerized static visual fields. Fundoscopy showed the presence of multiple bilateral peripheral arteriolar segmentation, without signs of vasculitis ([Fig. 1]). FA revealed several sites of arteriolar wall hyperfluorescence in areas of normal vascular permeability ([Fig. 2a]), as well as multiple peripheral retinal arterial occlusions ([Fig. 2b]). The sites of retinal arterial occlusion were not localised at arterial bifurcations, excluding the possibility of embolism.

Fig. 1 Colour photograph revealing multiple peripheral retinal arteriolar occlusions.

Fig. 2 Fluorescein angiography revealed peripheral arteriolar wall hyperfluorescence distant to areas of an arteriolar occlusion (a 10 minutes after dye injection) and an occlusion of a peripheral arteriole (b 5 minutes after dye injection).

Indocyanine-green angiography (ICGA) performed on initial evaluation revealed hypefluorescence of retinal arterial walls. The ICGA vascular retinal lesions were less numerous but corresponded to the sites which were hyperfluorescent on FA. ICGA revealed segmental hyperfluorescence of retinal arterial segments ([Fig. 3a]) as well as a few isolated circular hypofluorescent spots ([Fig. 3b]), corresponding to non-perfusion of choriocapillaris. Additionally, in the late phase of ICGA, segmental staining of choroidal vessels was also present ([Fig. 3c]).

Fig. 3 Indocyanine-green angiography results were remarkable for disclosing persistent staining of an arterial retinal branch (a arrow; 31 minutes after dye injection). In the intermediate phase (b 12 minutes after dye injection) there was a parapapillary dark spot (arrow), interpreted as a circumscribed zone of choroidal capillary non-perfusion. Finally, some staining of choroidal vascular segments (arrow), which becomes apparent only in the late phase of ICGA (c arrows; 28 minutes after dye injection).

A diagnosis of Susac’s syndrome was made and the patient was treated with prednisone and azathioprine. Neurological outcome was favourable, visual symptoms (flashing lights) disappeared, but a mild hearing deficit persisted. Follow-up and adjustement of immune-suppressive therapy was then based on the results of FA and ICGA (i. e. presence or absence of retinal arteriolar wall hyperfluorescence). Eventually results of FA and ICGA became normal and therapy was stopped in September 2008. The patient is in remission since.

The exact pathophysiology of Susac’s syndrome is not known yet, but it is believed to be an immune disorder leading to a micro-angiopathy of the pre-capillary arterioles of the brain, retina and inner ear. However, brain biopsies have only revealed wall sclerosis of small arteries and multi-focal micro-infarcts, without signs of inflammation. A true vasculitis was not present but some perivascular inflammatory infiltrates of cerebral arteriolar branches have been identified [6]. Similarly, there is neither a cellular reaction in the cerebro-spinal fluid, nor any suggestion of systemic inflammation on blood studies. Nevertheless, a favourable response to immuno-suppressive therapy supports the possibility of an immune-mediated condition [2].

The retinal vasculopathy of Susac’s syndrome is believed to result from an endotheliopathy. In a histopathologic description of a retina from a patient with Susac’s syndrome, the arterial lumens were narrowed by serous deposits. The fluid originated from inner blood-retinal barrier breakdown caused by dysfunctional endothelial cells. This report revealed that retinal vessels of all calibers were involved and that retinal veins were also targeted by the disease. Furthermore, focal areas of retinal capillary drop-out were found on ADPase-incubated retina [7]. Our patient showed hyperfluorescence of retinal arteriolar segments in ICGA, at the same location as identified in FA. Hyperfluorescent retinal vascular lesions detected by FA outnumbered those seen by ICGA. Fluorescein molecules are water-soluble and of small size, susceptible to leak from a small blood-retinal barrier breakdown, whereas indocyanine-green molecules are larger and bound to proteins, requiring an extensive blood-retinal barrier breakdown to leak. Small/mild retinal vascular lesions will leak only on FA, whereas large/severe lesions will leak on both FA and ICGA.

Although there is no histological evidence of choroidal involvement in Susac’s syndrome, a similar process of choroidal endotheliopathy and capillary drop-out, as the one identified in the retina, could be theoretically present in some patients with Susac’s syndrome. Our patient showed small circumscribed areas of choriocapillaris drop-out responsible for the dark dots identified in late ICGA frames in the case reported here. A unique finding in this case was late staining of choroidal vascular segments, observed in the first ICGA performed during the active phase of the disease, which were no longer visible in subsequent ICGAs whilst under treatment. We suggest that this finding may represent increased disease severity as it rapidly regressed under treatment, in contrast with retinal vascular hyperfluorescence which presented a persistent, fluctuating course, despite proper treatment and neurological remission.

Choroidal lesions detected by ICGA in a patient with Susac’s syndrome are reported here for the first time. We believe that these findings might represent a more severe stage of endotheliopathy in the context of the disease.

Conflict of Interest: None

• References

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