Ординатура / Офтальмология / Английские материалы / Mechanisms of the Glaucomas_Shields, Tombran-Tink, Barnstable_2008

Fig. 1. Typical appearance of eye with elevated episcleral venous pressure. These veins are distinguished from anterior ciliary arteries by the small tributaries near the limbus, which converge into increasingly larger, tortuous veins posteriorly.

There are several mechanisms of elevated EVP, including obstructive disorders, arterio-venous shunts, and idiopathic, that can lead to elevated IOP and glaucomatous damage. In this chapter, we will consider these different mechanisms and associated forms of glaucoma.

OBSTRUCTIVE MECHANISMS OF ELEVATED EPISCLERAL VENOUS PRESSURE

Graves’ Ophthalmopathy

Graves’ ophthalmopathy (GO) is the most common example of an obstructive mechanism of elevated EVP. It is derived from an autoimmune process of the thyroid gland, in which stimulatory autoantibodies bind to the thyroid-stimulating hormone receptor (TSHR) and activate gland function, leading to hyperthyroidism and a number of different clinical findings. Some of these findings are manifested in localized regions of connective tissue and include GO and dermopathy (7). Although hyperthyroidism is characteristic of the disease, approximately 10% of patients with GO have normal or even low hormone levels, but the majority have laboratory evidence of a thyroid autoimmune disease (8).

It is important to distinguish between hyperthyroidism, or thyrotoxicosis, in which there is increased sympathetic tone and lid retraction, but no exophthalmos or orbital abnormality, as compared to GO, also called endocrine ophthalmopathy or Graves’ orbitopathy or disease, in which there is true exophthalmos, because of space occupying abnormalities of the orbit. This chapter is concerned primarily with the latter condition.

Graves’ eye disease can be painful, cosmetically distressing, and sight threatening. The reported prevalence of visual disturbance among Graves’ patients is high, with a study in the United Kingdom revealing an estimated rate of 37.5% (25–50%). Ocular hypertension or associated open-angle glaucoma has been reported to occur in 5–24% of patients with GO (9–11). However, other studies have indicated lower prevalences of open-angle glaucoma in patients with Graves’ disease, in the range of 0.4–0.8%

(12,13), Ohtsuka et al., in a prospective study of 104 consecutive Japanese patients with Graves’ diseases, who underwent a complete ophthalmic examination, including applanation tonometry, exophthalmometry, automated static threshold perimetry, and computed tomography of the orbit, found that 14 (13%) exhibited typical glaucomatous visual field defects in the absence of compressive optic neuropathy (14). However, the IOP in 7 of the 14 patients was consistently less than 21 mmHg, during the follow-up period. Thus, these patients were diagnosed as having normal-tension glaucoma. Of the 104 patients, 23 (22%) were diagnosed as having ocular hypertension.

Graves’ disease, as with most autoimmune processes, is more prevalent in females, being six to eight times more common than in males. The disease most often occurs between the ages of 30 and 50 years, suggesting that yet unidentified age-related factors and/or hormonal changes may contribute to enhanced susceptibility (7).

Ocular Features

Symptoms described by patients with GO include a gritty sensation in the eyes, sensitivity to light, increased tearing, double vision, blurring of vision, and a feeling of sensation of pressure behind the eyes (15).

On physical examination, any of the following may be detected: extraocular muscle dysfunction, proptosis (forward protrusion of the eyes), periorbital and eyelid edema, conjunctival chemosis (swelling) and injection (redness), lid lag and retraction (or stare), or exposure keratitis (corneal injury due to dryness). Most patients experience only the minor congestive signs of chemosis, injection, and lid edema, with spontaneous improvement in several months. In a minority of patients, however, the disease progresses, and one or more of the clinical features (proptosis, extraocular muscle dysfunction, and periorbital edema) may become severe and remain symptomatic for several years. Less commonly, patients may develop compressive optic neuropathy or associated open-angle glaucoma with decreased visual acuity, diminished color perception, visual field defects, and rarely, blindness (7,16).

Theories of Glaucoma Mechanism

The autoimmune process that occurs with this disease is believed to be related to alterations of connective tissue rather than thyroid dysfunction (7). The direct alteration related to aqueous obstruction has been reported to be increased mucopolysaccharide deposition within the trabecular outflow system (9).

Wessely, in 1918, described increased IOP on upgaze in patients with Graves’ orbitopathy, which is now known to be due to inelasticity of the inferior rectus muscle from fibrosis, preventing relaxation and causing compression on the globe as the antagonist superior rectus muscle pulls the eye upward (7).There are several theories as to the possible causes of increased IOP in patients with thyroid-associated ophthalmopathy: (i) increased EVP, resulting from enlargement of the extraocular muscles and orbital congestion and infiltration; (ii) increased mucopolysaccharide deposition in the trabecular meshwork with a subsequent increased resistance to outflow; (iii) genetically linked predisposition to glaucoma and thyroid disease; and (iv) compression of the globe by fibrotic and enlarged rectus muscles in some gaze positions (17).

Management

The first treatment option is medical management of the thyroid dysfunction. Direct control of the glaucoma may involve aqueous suppressants and prostaglandins although these do not effect the EVP and do not work well when elevated EVP is the mechanism of the elevated IOP. Alpha-2 agonist have been reported to possibly have an effect on the EVP. However, laser trabeculoplasty is not indicated in post-trabecular glaucomas. When medical treatment fails, the preferred surgical procedure may be influenced by the degree of lid retraction. It may not be safe to have a trabeculectomy, especially with a thin, avascular bleb that is close to the limbus, if lid retraction allows chronic exposure of the bleb. In such cases, a fornix-based trabeculectomy, with a posterior bleb, could be performed, or a tube implant is another good option for cases with significant lid retraction (17). With any intraocular procedure in eyes with elevated EVP, uveal effusion and expulsive hemorrhage are potential complications.

In one study, patients who underwent orbital decompression or radiation therapy for their thyroid orbitopathy were reported to have a significant reduction in IOP (18) (see Fig. 1).

Cavernous Sinus Thrombosis

The CSs receive their blood supply from the superior ophthalmic vein, the cerebral veins and the sphenoparietal sinuses, and terminate posteriorly in the superior and inferior petrosal sinuses, which drain into the transverse sinuses and internal jugular veins (19). CS thrombosis, or thrombophlebitis, is a rare but potentially lethal disorder, which is most often a complication of sinusitis or orbital cellulites (19,20). As such, it is considered to be a true ocular emergency. Mortality has decreased from nearly 100% in the pre-antibiotic era to 20–30% after the availability of antimicrobial agents (21–23). It may occur as a complication of infectious (septic) or non-infectious (aseptic) processes. Spread to the opposite eye may appear within 24–48 h of the unilateral onset by extension through the intercavernous sinuses (19,20,24). A chronic form has also been described (25).

In addition to sinusitis and orbital cellulites as the most common sources (20), other reported causes of CS thrombosis include odontogenic infections (gingivitis, dental abscess), parapharyngeal abscesses, facial abscesses, otitis, meningitis, cervicofacial infections, internal carotid artery occlusion in polycythemia vera (26), dural-cavernous fistulas (27), high-dose corticotherapy, intravenous cyclophosphamide for the treatment of lupus nephritis (28), cataract extraction and IOL implantation (29), third molar removal (30), transsphenoidal craniotomy (31), bone marrow transplantation (32), and cranial trauma.

The most common etiologic agent in patients with septic CS thrombosis is Staphylococcus aureus, which is found in 60–70% of cases (19). Less frequently identified are Streptococcus pneumoniae, Streptococcus milleri (20), Gram-negative bacilli, anaerobes and the fungi, zygomycosis and mucormycosis (19,20). Blood cultures are positive in approximately 70% of cases, especially in patients with acute, fulminant disease, whereas cerebrospinal fluid is culture positive in approximately 20% of cases (19).

General Features

Systemic signs and symptoms include the effects of sepsis and toxemia, such as fever and lethargy, as well as those associated with the underlying disorder, such as meningitis, subdural empyema, pituitary necrosis with hypopituitarism (19,33), brain abscess (34,35), hemiparesis, hemiplegia, seizures, odynophagia, and dysphagia (19).

Ocular Features

The most common ocular signs and symptoms are those associated with the structures which are closely related to the CSs, that is, cranial nerves III, IV, first and second division of V, VI, and the horizontal segment of the internal carotid artery (19,36). The majority of the patients present with ptosis, proptosis, chemosis, external or complete ophthalmoplegia with paralytic mydriasis or miosis, absence of corneal reflex, venous stasis in the fundus of the eye, and papilledema. Less common findings are decreased visual acuity, nystagmus and diplopia (19), exposure keratopathy (20), ocular neuromyotonia (34), multiple emboli in the central retinal artery (37), central retinal vein occlusion (38), ophthalmic artery occlusion (26), ischemic optic neuropathy (39) and blindness (39,40).

CS thrombosis is one of the many causes of painful ophthalmoplegia, and by far, the most dramatic in presentation. The differential diagnosis includes orbital cellulitis (19, 36,41), intraorbital abscess (20), orbital apex syndrome, granulomatosis, Tolosa–Hunt syndrome, internal carotid aneurysm, carotid-cavernous fistula, and ophthalmoplegic migraine.

Theories of Glaucoma Mechanism

Glaucoma in this condition is usually secondary to EVP increase, as the CS thrombosis obstructs venous flow through the superior ophthalmic vein, which is the main venous drainage route of the orbit. The prevalence of associated glaucoma in this disorder is unclear, possibly due to the fact that the patients are often seen first by the internist or neurologist and, therefore, early attention is not always given to the elevated IOP. There have also been rare reports of associated acute angle-closure glaucoma from a uveal effusion, with forward displacement of iris–lens diaphragm (28,42).

Management

The most important diagnostic procedures are computed tomography, magnetic resonance imaging (24), angioresonance (43), transcranial venous Doppler ultrasonography, and ultrasonography of the eye and orbit.

The success of therapy depends on prompt recognition and systemic treatment with the appropriate broad spectrum antibiotics (usually for many weeks) (19,20, 36), as well as close observation for and immediate treatment of complications and sequelae. Additional treatments that are controversial and not universally accepted include systemic corticosteroids (19,44), anticoagulant therapy I (19,20), which has the risk of recurrent hemorrhages (36), tissue plasminogen activator (TPA), intrasinusal thrombolysis, and rheolytic thrombectomy. Surgical drainage of abscesses is usually indicated (20,24).

In managing the glaucoma, drugs that reduce aqueous humor production are usually preferred. Drugs that facilitate trabecular outflow are less effective, as the mechanism of

elevated IOP is increased EVP. The role of prostaglandin analogs is still not well established, but they may have value in these cases. For angle-closure glaucoma, drainage of the ciliochoroidal effusion or choroidal detachment may be necessary (27). However, as restoration of orbital venous flow typically occurs in a few weeks, with normalization of EVP, surgical intervention for the glaucoma can often be avoided. These patients usually have healthy optic nerves and no significant risk factors for glaucoma prior to the thrombotic event so that relief with ocular hypotensive agents even with persistent IOP elevation may be temporarily sufficient. However, close observation during the active period of the disease is necessary. If surgical intervention is determined to be necessary, a filtration surgery is most often the preferred approach although the increased risk of uveal effusion and expulsive hemorrhage must be considered. The risk of these complications can be reduced by prophylactic sclerotomies for drainage of any suprachoroidal fluid.

Vena Cava Obstruction and Ocular Hypertension

Although there are few reports in the literature, an obstruction of the vena cava can obstruct the venous return from the head, thereby causing elevated EVP with associated exophthalmos, periorbital edema, and cyanosis. Mechanical ventilation could also cause an increase of superior vena cava pressure and should, theoretically, increase EVP and IOP. Johnson et al. reported an IOP elevation of 32.7% during peak inspiratory pressures compared with that at the end of the supine, spontaneous ventilation control period (45).

Tricuspid Incompetence

Tricuspid incompetence in transmitting ventricular pressure, with reversed flow in the superior veins, can lead to increase of EVP and associated glaucoma. Color Doppler imaging may assist in making this diagnosis (46).

Retrobulbar Tumors

Retrobulbar tumors may cause IOP elevation, by either increased EVP or direct compression of the eye. A rise in EVP in association with orbitral tumors is relatively uncommon, as the distensibility of the optic nerve allows the globe to be displaced anteriorly with proptosis, but usually without significant obstruction of the venous drainage.

ARTERIO-VENOUS SHUNT MECHANISMS OF ELEVATED EPISCLERAL VENOUS PRESSURE

Sturge–Weber Syndrome

The association between facial vascular abnormalities and glaucoma was first reported in the 19th century (47,48). In 1860, Schirmer (49) described the coexistence of bilateral facial port-wine nevus and unilateral buphthalmos in a 36-year-old man but did not mention any neurological findings. Sturge (50) described the full syndrome of dermal, ocular, and neurological abnormalities in 1879, and Weber (51) detailed the neurologic radiological findings of the cortex in 1922.

The syndrome is defined as a rare, sporadic neurocutaneous disorder that affects cephalic microvasculature and is characterized by facial capillary malformation of the trigeminal distribution, ipsilateral leptomeningeal angioma, and ocular vascular abnormalities. The syndrome has also been called encephalotrigeminal angiomatosis. There is no gender predilection, and familial cases are rare. Its prevalence is estimated at 1 per 50,000 live births although the recent identification of milder forms of the syndrome has led to an increase in the estimated frequency (47,48,52,53).

Sturge–Weber syndrome likely results from an early embryologic malformation of vascular development of the skin, eye, and brain. Studies suggest that complex molecular interactions contribute to this abnormal development and function of blood vessels in Sturge–Weber syndrome. Neurological deterioration in Sturge–Weber syndrome is most likely secondary to an impaired blood flow to the brain and is worsened by the presence of seizures (53,54).

General Features

The major hallmarks of Sturge–Weber syndrome are as follows:

1.Facial port-wine stain nevus in the V1 or V2 regions of the trigeminal cranial nerve.

2.Dural and leptomeningeal angiomatosis, which can be diffuse and bilateral, but most often affects occipital and posterior parietal lobes unilaterally.

3.Hemangiomas of the choroid and conjunctival telangiectasias.

4.Glaucoma.

These findings may vary from partial to complete manifestation, and Sturge–Weber syndrome is classified into three types according to clinical presentation. In type I (classic form), patients present with facial, choroidal, and leptomeningeal angioma, with possible glaucoma. In type II, there is only facial port-wine stains, with no endocranial involvement, and in type III, there is only the meningeal angioma (47,48,52,53).

The cutaneous findings are typically present at birth and affect the V1 and V2 regions of the trigeminal nerve. The vascular abnormalities are well demarcated and have port-wine or salmon color, which darkens with increasing age. They are typically flat and blanch under pressure but may assume a tuberous or hypertrophied aspect. In addition, pyogenic granulomas or acral arteriovenous tumors may develop, and bilateral lesions can be seen in 10–30% of the patients (47,48,52).

Neurological manifestations can include seizures, intellectual impairment, hemiparesis, hemianopsia, and migraines. Epilepsy is seen in 75–90% of cases, with the majority developing before 2 years of age. With advancing age, the seizures tend to become more severe, frequent, and complex. Pharmacological control of the epilepsy is possible in approximately 40% of patients. Mental retardation is present in almost a half of the patients and may be related to epilepsy, as it is more common in children whose seizures begin before the age of 2 years or who have seizures that are not clinically controlled. Additionally, neurologic venous occlusions and hypoxia may be contributing factors to the mental retardation. Headaches affect 30–45% of patients and frequently present as migraine-like episodes, resulting from vasomotor disturbances within and around the angioma. Additional neurologic manifestations include contralateral hemiparesis, hemiplegia, and hemianopsia, which are frequently

preceded by prolonged seizures. Seizures, development delay, and focal deficits are more frequent in patients with bilateral leptomeningeal angiomatosis, which occur in 7–26% of patients. Leptomeningeal angiomatosis are more frequent in the parietooccipital area, and cerebral atrophy and calcifications are common radiological findings. Magnetic resonance imaging is the gold standard for identification of the structural brain abnormalities (47,48,52,55–58).

Ocular Features

The ocular component manifests as glaucoma and vascular malformations of the conjunctiva, episclera, choroid, and retina (47,48,52,59–61). Sullivan et al. (60) reported the ocular findings in 51 consecutive Sturge–Weber patients and found that 36 (71%) had glaucoma (with 26 before 24 months of age), 35 (69%) had conjunctival or episcleral hemangiomas, and 28 (55%) had choroidal hemangiomas. Twelve of the cases were bilateral. Other ocular manifestations included retinal vascular tortuosity, iris heterochromia, retinal detachment, and strabismus. Sixty-seven percent of the glaucomatous eyes had a final visual acuity of 20/40 or better or a central, steady, and fixed gaze.

Glaucoma is the most common ocular manifestation of Sturge–Weber syndrome, and a review of the literature revealed a reported prevalence ranging from 30 to 70% of the patients (47,48,52,53,59,60,62). It can be present at birth or develop later, with the most frequent onset around 6 years of age. The glaucoma is typically ipsilateral to the facial lesion, but bilateral cases can occur with unilateral facial stain. The glaucoma tends to develop insidiously, and IOP is often markedly elevated. Patients in whom the vascular lesion affects the upper eyelid are at increased risk of developing glaucoma (59).

Diffuse choroidal hemangioma, ipsilateral to the port-wine stain, is a characteristic feature of the syndrome that may be found in up to 71% of cases (48,60,61). It is usually seen as a red, flat to moderately elevated mass, which produces a classic “tomato ketchup” appearance upon fundoscopic examination (63). This appearance is in contrast to choroidal hemangiomas that are not associated with Sturge–Weber syndrome, which are discrete and raised. With time, choroidal hemangiomas produce secondary changes in the overlying retina, such as retinal pigment epithelium degeneration, fibrous metaplasia, and cystic retinal degeneration, leading to loss of vision and visual field defects. Continuing exudation of the hemangioma may also cause retinal detachment. Choroidal hemangiomas are almost always associated with leptomeningeal hemangiomas, and neuroimaging is mandatory when fundoscopic evaluation reveals a choroidal hemangioma.

Dilated and tortuous episcleral vessels are reported to occur in approximately 69% of cases (60). Buphthalmos, optic disc coloboma, and cataracts have also been reported. Sturge–Weber syndrome has been described in association with Nevus of Ota (unilateral increased skin pigmentation in the trigeminal distribution with ipsilateral pigmentation of ocular structures and frequently associated glaucoma) (64,65), iris neovascularization and heterochromia (66,67), and bilateral retinitis pigmentosa with a dislocated lens (68).

Studies with ultrasound biomicroscopy in patients with Sturge–Weber revealed supraciliary effusion and dilated episcleral and intraciliary vessels. Sakai et al. (69) reported ciliochoroidal effusion, induced by topical latanoprost, which is probably due to the enhanced uveoscleral outflow (70–72).

Sudden onset of intraoperative choroidal effusion has been reported in 10–40% of Sturge–Weber syndrome patients undergoing glaucoma filtering surgery or any other introcular procedure, and expulsive choroidal hemorrhage has also been reported in cases of Sturge–Weber syndrome.

Visual loss in patients with Sturge–Weber syndrome is secondary to glaucoma or from damage to the retrogeniculate pathways by the angiomatous lesions. Rarely, nonglaucomatous optic neuropathy may develop and contribute to progressive visual loss (73). Homonymous hemianopsia may occur secondary to occipital lobe involvement, and central vein occlusion has been reported in young adults with Sturge–Weber syndrome, without any other predisposing factors other than high IOP.

Theories of Glaucoma Mechanism

Glaucoma secondary to Sturge–Weber syndrome may occur by two possible mechanisms. The first is related to a developmental anomaly of the outflow pathways and the second is associated with elevated EVP, which is due to small arteriovenous fistulas in the episcleral vessels (74).

Developmental anomaly of anterior chamber angle appears to be the major mechanism for IOP elevation in the early onset forms of glaucoma, especially those associated with buphthalmos. Histopathological studies have revealed anomalies in the trabecular meshwork and Schlemn’s canal. Mwinula et al. (75) reported light and electron microscopic findings of a trabeculectomy specimen, which showed multiple congenital anomalies, with a cluster of blood vessels in the trabecular meshwork and abnormal accumulations of fine granular extracellular matrixes in both the juxtacanalicular connective tissue and around the vascular structures. The lumen of the Schlemm’s canal was subdivided into three or four parts, with few giant vacuole structures. The endothelial cells lining the inner wall of the Schlemm’s canal contained a well-formed basal lamina, with many villi projecting into the lumen. Akabane and Hamanaka (76) reported histological findings of trabeculectomy specimens, which showed that the ciliary muscle was dislocated anteriorly and the Schlemm canal was not present. The spaces in the juxtacanalicular connective tissue were replaced by connective tissue and vascular structures with or without pericytes surrounding the endothelium. The authors concluded that the developmental abnormalities of both the mesoderm and the neural crest cells might be involved in the pathogenesis of the glaucoma in cases of Sturge–Weber syndrome.

The later onset cases of glaucoma in Sturge–Weber syndrome are probably related to vascular abnormalities. Small arteriovenous fistulas in the episclera may elevate the EVP and cause glaucoma. Phelps found EVP to be markedly elevated in 15 of 16 patients with Sturge–Weber syndrome and glaucoma. In another study, he examined 21 patients with the disease and found that 16 patients had glaucoma, of which 3 were bilateral (74). Episcleral hemangiomas were visible in all of the glaucomatous eyes, and the more extensive the hemangioma, the more severe was the glaucoma.

During gonioscopy, blood could easily be made to reflux into the Schlemm’s canal of glaucomatous eyes and often the canal separated into multiple fine channels. We measured EVP in 11 patients with Sturge–Weber syndrome and found elevations in all of the glaucomatous eyes, suggesting that glaucoma in Sturge–Weber syndrome is often caused by elevated EVP. Most likely, veins draining aqueous fluid from the canal of Schlemm are part of an intrascleral or episcleral hemangioma although the canal of Schlemm may also contain part of the hemangioma. Arteriovenous shunts in the hemangioma raise EVP, which in turn elevates IOP (74).

Management

The treatment of glaucoma in patients with Sturge–Weber syndrome is usually difficult, with poor medical results and an uncertain optimum surgical approach (62). Medical treatment may have some value in the late onset forms of glaucoma, but most drugs have limited efficacy. In one report, ciliochoroidal effusion occurred in a 17-year-old boy with Sturge–Weber syndrome, which was thought to be related to latanoprost (69). It was postulated that a combination of enhanced uveoscleral outflow, with latanoprost, and elevated EVP may have caused congestion of the aqueous humor in the supraciliary choroidal space, resulting in the ciliochoroidal effusion.

Trabeculotomy and goniotomy have both been used for congenital cases (77–79). Some series report satisfactory results with a combined trabeculotomy–trabeculectomy procedure. Mandal (77) analyzed 10 eyes of 9 patients with Sturge–Weber syndrome, who underwent the combined procedure and reported that all eyes maintained a postoperative IOP <16 mmHg, without medication, over a mean follow-up period of 27.6 ± 16.4 months (range = 12–64 months). Normal corneal clarity was achieved in all eight eyes that had corneal edema, and there were no significant intraoperative complications. Similar results were reported by Irkec et al. (78) and Board and Shields (80). Trabeculectomy alone is also an option (81,82).

Some studies have revealed higher incidences of choroidal hemorrhage and expulsive hemorrhage, associated with filtering procedures in Sturge–Weber syndrome (83,84) although Eibschitz-Tsimhoni (85) did not encounter either in 17 consecutive patients who underwent glaucoma filtering procedures.

Glaucoma implants have also been used to treat glaucoma secondary to Sturge– Weber syndrome. Budenz et al. (86) reported the results of two-stage Baerveldt implants in 10 children and found that all eyes had adequate IOP control (≤21 mmHg), without the need for additional glaucoma surgery. IOP was reduced from a mean of 24.8 ± 6.2 mmHg, preoperatively, to 16.9 ± 2.3 mmHg (p = 0.001), with an average follow-up of 35 months (range = 10–50). The number of glaucoma medications was reduced from a mean of 1.8 ± 1.0, preoperatively, to 1.1 ± 1.4 (p = 0.2). Two eyes had serous choroidal effusions, but there were no suprachoroidal hemorrhages. Visual acuity improved by one or more lines in all patients with measurable vision. Hamush et al. (87) reported cumulative probability of success with Ahmed valves to be 79% [95% confidence interval (CI) = 52–100) at 24 months, 59% (95% CI = 20–98) at 42 months, and 30% (95% CI = 0–75) at 60 months. Other therapeutic options include diode laser cyclophtocoagulation (88).

Carotid-Cavernous Fistula

Arterial-venous fistulas (AVF) are characterized by abnormal shunting of blood between the arterial and the venous systems, without the presence of a normal intervening capillary bed. Because the capillary bed is the source of resistance to blood flow in the circulatory system, these fistulas produce low resistance and high flow

(89,90).

A carotid-cavernous fistula (CCF) is an AVF that occurs between major cerebral arteries and/or their branches, which drain directly or indirectly into the CS. They are the most frequent AVF in the central nervous system. Those which arise from a defect in the cavernous segment of the internal carotid artery are called a direct fistulae because the drainage into the CS arises directly from the internal carotid artery. If the CCF results from an AVF supplied by external and internal carotid artery dural branches, it is called indirect, or dural, fistula (91,92). Because the CS receives blood supply from the sphenoparietal sinuses and the orbits by way of the ophthalmic veins, venous drainage from the globe is directed toward the CS by way of the ophthalmic veins, and the arteriovenous shunt in the CS reverses flow in the orbital veins (90). The etiology of the arterial-venous “short-circuit” can be divided into two categories: traumatic and spontaneous (93).

General Features

Some patients complain of headache and facial pain in the area of the trigeminal innervation. In a spontaneous CCF, the most common initial findings are red eyes, orbital bruit, and headaches (94). Patients may also present with profound nasal bleeding and potentially fatal intracerebral hemorrhage (95). Traumatic CCFs are typically more dramatic, especially with severe head trauma, and the venous pressure is usually very high.

The diagnosis is usually confirmed by the carotid arteriography (5). Carotid Doppler ultrasound, magnetic resonance imaging, or computerized tomography scanning may also be helpful when the arteriographic findings are inconclusive as in small fistulas with a discrete increase of venous pressure (96–101).

Ocular Features

The most common ocular symptoms are red eyes, orbital pain, blurred vision, diplopia, and auditory pulsations (102,103). The main ocular signs are pulsatile exophthalmos, orbital bruit on auscultation, engorgement and tortuosity of the conjunctival, episcleral and orbital vessels, eyelid edema, conjunctival chemosis, palpation of globe, choroidal detachment, disc edema, and uveal congestion. Additional findings may include retinal hemorrhage, retinal vasodilatations, proliferative retinopathy, occlusion of the central retinal vessel, and vitreous hemorrhage. The severity of the clinical signs depends on the degree of elevated EVP, as well as its pathogenesis (102,104,105). Dural CCFs, which drain primarily into the inferior petrosal sinus, may cause painful oculomotor palsies that are difficult to diagnose because they lack congestive orbitoocular features (106).