Carotid-Cavernous Sinus Fistula Masquerading as Thyroid Eye Disease

A 29-year-old man with a medical and social history notable for smoking presented with progressive orbital congestion, conjunctival injection, and extraocular muscle enlargement consistent with thyroid eye disease (TED). On ophthalmologic examination, tortuous episcleral vessels and blood in Schlemm’s canal on gonioscopy clued an alternative diagnosis. Cavernous sinus enhancement on computed tomography also suggested a retro-orbital process. Digital subtraction angiography confirmed a low-flow indirect carotid-cavernous fistula (CCF). He subsequently underwent endovascular embolization treatment. Ocular symptoms resolved by seven weeks, and he remained ocular symptom free at six months. Eye redness and proptosis frequently cause patients to seek medical attention. In the absence of a mass or signs of infection, TED is high on the differential, especially with a smoking history and even with normal thyroid parameters. However, CCF may lurk; the authors describe key diagnostic features and management.


Introduction
First classified by Barrow et al. in 1985, carotid-cavernous fistula (CCF) is a rare cerebrovascular connection between the intracranial carotid arterial system and the cavernous sinus [1]. The diagnosis of CCF may be challenging. Several of the symptoms, including diplopia, progressive proptosis, conjunctival injection, and ophthalmoplegia, mimic thyroid eye disease (TED). While normal thyroid parameters do not rule out TED, subtle ophthalmologic findings can suggest the correct diagnosis of CCF. We present a case of CCF initially misdiagnosed as TED and describe the key clinical findings and management.

Case Presentation
A 29-year-old man presented with a one-year history of right conjunctival injection, progressive proptosis, and diplopia. Past medical history and social history included self-limited Bell's palsy five years prior and 15-pack-year history of smoking. He denied any major trauma but four years earlier had suffered a contusion of the right periorbital region after a minor motor vehicle crash for which he did not seek medical attention. Review of the systems was negative for vision loss, pain, fever, headache, weight loss, fatigue, or heat intolerance. One year ago, an outside provider diagnosed him with TED, for which he was sent to our institution for management.
On ophthalmologic examination, visual acuity measured 20/20 in each eye. Intraocular pressures were normal (21 and 19 mmHg in the right and left eyes, respectively). No pupillary abnormality or relative afferent pupillary defect was detected. External examination revealed right proptosis, periorbital edema, and conjunctival injection ( Figure 1A). Extraocular movements demonstrated generalized ophthalmoplegia of the right eye most noticeable on abduction. Left eye movements were full.
Computed tomography (CT) scan of the orbits revealed enlarged extraocular muscles that, with the smoking history and clinical findings, corroborated a suspicion for TED ( Figure 1B). Serum thyroid studies were normal (thyroid stimulating hormone: 2.37 mIU/L, T3: 125 ng/dL, and T4: 1.0 ng/dL), but euthyroid TED was a leading presumptive diagnosis.
Slit lamp biomicroscopy of the right eye showed dilated and tortuous episcleral vessels. Gonioscopy revealed blood in Schlemm's canal. Retinal examination demonstrated dilated, tortuous vessels. The left eye examination was unremarkable. Attention to retro-orbital and intracranial aspects of the CT revealed right cavernous sinus enhancement ( Figure 1C). These findings prompted suspicion for an intracranial vascular abnormality for which angiography was indicated. Digital subtraction arteriography (DSA) redemonstrated cavernous sinus opacification arising from branches of the right internal carotid artery (ICA) and external carotid artery (ECA). Flow reversal of the cavernous sinus into the right superior ophthalmic vein was consistent with a low-flow ICA-ECA CCF (Figure 2A). The patient subsequently underwent endovascular embolization of the CCF with the liquid embolic system, Onyx® (EV3, Irvine, CA, USA).
Examination one day later revealed improvements in conjunctival injection and abduction ( Figure 2B). Three weeks post-operatively, proptosis improved dramatically. At seven weeks, the motility deficit and conjunctival injection resolved. At six months, he continued to have no central nervous system (CNS), orbit, or ocular issues.

Discussion
CCF is a rare, sight-and CNS-threatening disorder characterized by abnormal communication between the cavernous sinus and the ICA, ECA, or their branches [2]. CCFs may be direct high-flow shunts between the ICA and cavernous sinus and associated with trauma in young males [1,2]. Indirect low-flow shunts are typically spontaneous in older females and occur between the cavernous sinus and branches of the ICA, ECA, or both [1,2]. Rarely, trauma may induce indirect CCF [3].
Unilateral or bilateral progressive orbital congestion, proptosis, conjunctival injection, extraocular muscle enlargement, and smoking history are also hallmarks of TED, a much more common diagnosis than CCF. Importantly, normal thyroid parameters do not rule out TED as 5-10% of the cases are euthyroid [5].
Tortuous episcleral vessels and blood in Schlemm's canal, while possible secondary to TED, suggested a more serious cause for orbital venous outflow abnormality. Cavernous sinus enhancement on CT also clued a retro-orbital process, and DSA confirmed the diagnosis of indirect ICA-ECA CCF.
Although subtle, history and examination can suggest CCF. Diagnosis is confirmed with neuroimaging. Carotid DSA remains the gold standard, with endovascular embolization the primary treatment [1,2]. Prognosis after endovascular treatment is excellent, with visual acuity preserved or improved in 94% of the cases [4].