Ординатура / Офтальмология / Английские материалы / Clinical Pathways in Glaucoma_Zimmerman, Kooner_2001

110 Glaucoma Associated with Raised Episcleral Venous Pressure: The “Red Eye“ Glaucomas

ous veins pass from the deep sclera to the episcleral plexus. Under conditions of increased episcleral venous pressure, the flow will be reversed and blood is frequently seen in Schlemm’s canal with simple gonioscopy.7

What Affects the Aqueous Humor Dynamics?

In the steady state, the dependence of IOP on EVP is approximated by the modified Goldmann equation Po f/c Pev, where Po is the IOP, Pev is the EVP, f is the aqueous inflow, and c is the outflow facility. This equation states that for every 1 mm increase in EVP, there is a concomitant increase of 1 mm in IOP. Numerous studies have been done to test this hypothesis. In 1968, the validity of the Goldmann equation was first tested in humans.8 It was observed that for every millimeter of mercury increase in EVP, there was only a 0.75-mm increase in ocular pressure. The term pseudofacility is used to describe the decrease in inflow, secondary to an increase in IOP, and is frequently a part of a trick question given to ophthalmology residents, as follows: “What is the tonographic outflow facility in a patient with elevated IOP due to increased EVP?” There is a natural tendency to answer that the outflow facility is abnormal because, obviously, the IOP is elevated. This would be incorrect. The tonographic outflow facility, at least in the disease process, can be and usually is normal despite the elevated IOP. This phenomenon has been studied in normal volunteers using a blood pressure cuff placed around the patient’s neck. When it is inflated, the episcleral venous pressure becomes elevated, but the IOP increases to a slightly smaller degree. This effect is small and the overall phenomenon indicates that the aqueous humor formation does not self-regulate in response to the level of IOP.9 There are no known feedback loops or anatomic connections that would allow such a regulatory process to occur. It is tempting to speculate that a chronically elevated EVP could be an important factor in all chronic open-angle glaucoma, but this has not been demonstrated to be the case.10 However, for secondary types of open-angle glaucoma, episcleral venous pressure is important (Table 6–2).

Table 6–2. Ocular Findings Suggestive of Raised Episcleral Venous Pressure (EVP)

Slit-lamp exam for “red eye”; blood in aqueous veins Gonioscopy showing blood in Schlemm’s canal

Dilated fundus exam showing distension of retinal veins Extraocular motility exam showing duction deficiencies Arteriovenous fistula (AVF) screening tests showing neurologic cuts Orbital exam showing bruit, vascular anomalies, or traumatic scars Tonography sometimes helpful

Presence of exophthalmos—stable or pulsatile

Increased cup-to-disc ratio showing chronically increased IOP EVP measurement directly elevated

Ophthalmodynamometry showing arteriovenous malformations

Orbital ultrasound showing soft tissue masses—may increase with position changes

What Is Uveoscleral or Unconventional Outflow?

Bill11 was among the first to point out that flow through the trabecular meshwork and Schlemm’s canal seems to involve a well-designed fluid transport system. In contrast, uveoscleral flow seems more primitive and resembles a leak more than a well-designed fluid transport system.7 The aqueous humor enters the ciliary muscle fibrils through the uveotrabecular meshwork, the ciliary body space, and the root of the iris. Fluid passes between the bundles of the muscle until it reaches the supraciliary and suprachoroidal spaces. The aqueous humor leaves the eye through the spaces around the penetrating nerves and blood vessels and through the sclera. Even large molecules, such as horseradish peroxidase, can pass through intact sclera. Uveoscleral flow seems to be present in most species, but the amount of aqueous humor transported by the system varies considerably, being approximately 3% in rabbits and 50% in some species of monkey; in humans it is estimated that 5 to 25% of the total outflow is through this unconventional pathway. Direct measurement of uveoscleral flow is very limited, and the human eyes that have been studied may be atypical. Also, outflow increases up to fourfold when the anterior segment is inflamed. It appears that uveoscleral flow increases when the IOP is raised from atmospheric pressure to the level of the EVP; however, above this pressure level, uveoscleral flow is largely independent of IOP. The main resistance to uveoscleral flow is the tone of the ciliary muscles. Factors that contract the ciliary muscles, such as pilocarpine, lower the flow, whereas drugs that relax the ciliary muscles, such as atropine, increase the flow. The prostaglandins significantly increase uveoscleral outflow, and the effects of a prostaglandin/pilocarpine combination are largely unstudied. A few studies indicate that epinephrine may lower IOP by increasing uveoscleral outflow. Cyclodialysis is an older operation designed to lower IOP by detaching a portion of the ciliary body from the scleral spur. There is evidence that this acts to increase uveoscleral outflow.7

What Is the Normal Venous Drainage of the Orbit?

The main venous supply from the orbit is provided by the superior ophthalmic vein, the inferior ophthalmic vein, and the central retinal vein (Fig. 6– 1).12 The supply to the eyelids is supplemented by branches of the superficial temporal and facial veins. These vessels have no valves, are markedly tortuous, and display many plexiform anastomoses. They communicate with the veins of the face, with the pterygoid plexus, and with the veins of the nose. They ultimately drain into the cavernous sinus.

The superior ophthalmic vein is formed near the root of the nose via communication from the angular vein and the supraorbital vein. It passes into the orbit above the medial palpebral ligament and then accompanies the ophthalmic artery across the optic nerve and under the superior rectus to the superior orbital fissure, where it is usually joined by the inferior ophthalmic vein. It then leaves the orbit to enter the cavernous sinus. The inferior ophthalmic vein forms as a venous plexus on the orbital floor. It takes branches from the lower lid, tear sac, inferior rectus, oblique muscles, and the two inferior vortex veins. The blood flow passes posteriorly, forming two veins, getting into the medial compartment of the supraorbital fissure, and then into the cavernous sinus. A lower branch may pass through the intraorbital fissure to the pterygoid plexus.

112 Glaucoma Associated with Raised Episcleral Venous Pressure: The “Red Eye“ Glaucomas

Figure 6–1. Venous drainage of the orbit. Superior ophthalmic vein, inferior ophthalmic vein and facial veins are the three principal routes of orbital venous drainage. (From Ritch, Shields, and Krupin, 1999. By permission from C.V. Mosby.)

The central retinal vein is a confluence of all of the branches of the retinal venous circulation. The upper veins form a superior papillary vein and the lower and inferior papillary vein, which unite in the region of the optic cup. About 10 mm behind the globe, the central retinal vein turns downward at a right angle to leave the optic nerve. It usually passes through the sheath of the optic nerve and emerges behind the artery, where it runs posteriorly and passes through the oculomotor foramen to enter the cavernous sinus directly. The cavernous sinus drains primarily through the superoinferior petrosal sinuses into the internal jugular vein. A small amount drains through the external jugular veins, and still less through the suboccipital plexus into the vertebral and deep cervical veins. The cavernous sinus also has connections with the ipsilateral pterygoid plexus and the contralateral cavernous sinus. Facial veins communicate with the superior ophthalmic vein through the nasal, frontal, and lacrimal eyelid veins and communicate with the inferior ophthalmic vein through the infraorbital vein. The facial veins drain mainly into the external jugular veins.4,6

How Is the EVP Measured?

The episcleral vessels can easily be differentiated from the conjunctival vessels by the relative mobility of the latter when they are in touch with the tip of a pressure chamber (Table 6–3). The episcleral veins are differentiated from the anterior ciliary arteries by the narrower caliber, straighter course, and slightly darker color of the veins. Glaucomatous damage develops in certain patients because of elevated EVP. For an instrument to be practical in the clinical environment, it should be easily operated by one observer, require little calibration, be of compact size, permit stereopsis before and during the measurement, and provide good reproducibility. Such an instrument, called a venomanometer, has been developed by Zeimer and associates.13 Basically, the instrument is mounted directly on the slit lamp. It looks similar to an applanation tonometer. There is a flexible transparent tip of molded silicone rubber covering an air-sealed piston.

Table 6–3. Medical Evaluation of Patients with Increased Episcleral Venous Pressure (EVP)

Blood test for thyroid disease

Look for exophthalmos—stable or pulsatile Listen for bruit in orbit or neck

Do x-ray/computed tomography (CT) scan of skull, orbit, foramen Do electroencephalogram (EEG)

Examine carefully for skin lesions suggestive of congenital vascular disease or scars indicating trauma

Performing systemic measurement of venous pressure in arms Get a complete neurologic examination

Order selective external and internal carotid arteriogram Order orbital venogram

Consider digital subtraction angiogram or color Doppler ultrasound

There is a rotating dial that controls the position of the air-sealed piston. The position of the piston determines the volume of air in the chamber and therefore its pressure. The instrument is available currently for approximately $850 according to personal communications with Peter Netland, M.D., Ph.D.

The EVPs in normal eyes and in eyes with open-angle glaucoma have not been shown to be significantly different. However, Kupfer10 and Talusan and Schwartz14 have reported that ocular hypertensive eyes have a slightly lower EVP than normal eyes. There are some problems in measuring the EVP. Most of these problems are of an anatomic nature. Different observers may select different blood vessels, which may yield slightly different readings. Also, the selection of the end-point indication of increased EVP is somewhat arbitrary. Tissue compressibility has been reported to be negligible, and the pressure required to blanch the vessel to the one-half point accurately reflects the intraluminal pressure. No evidence has been found for regional differences in EVP within the quadrant of an eye or between the two eyes. There is a significant correlation of EVP with age. The normal EVP runs 7.6 ± 1.3 mm Hg. When the EVP is raised by some disease process, the IOP is usually increased as well; however, the relationship between the pressure increases is more complex in the chronic situation than in the acute, experimental situation. Many conditions, for example carotid cavernous fistula, that increase EVP also cause ocular ischemia, and that reduces the aqueous humor formation and IOP. Also, acute elevations of EVP increase the facility of outflow, whereas chronic elevations of pressure may produce secondary changes in the angle structures, and ultimately decrease the outflow facility.

What Clinical Conditions Cause Raised EVP?

Various clinical conditions may result in elevated EVP. As discussed below, patients may present with a multitude of ocular and/or systemic signs and symptoms. The steps in an evaluation include a history; measurement of visual acuity, IOP, and EVP; slit-lamp examination; neurophthalmic examination, gonioscopy; and fundus examination. Figure 6–2 delineates various steps that may help in the diagnosis.

114 Glaucoma Associated with Raised Episcleral Venous Pressure: The “Red Eye“ Glaucomas

Figure 6–2. Algorithm for diagnosing causes of increased EVP.

What Venous Obstruction Problems Cause Raised EVP?

Orbital venous abnormalities and lymphangiomas have been generally classified on morphologic grounds; however, this has led to a confusing scientific dialogue. The members of the Orbital Society have recently issued a statement classifying orbital vascular malformations based on their hemodynamic relationships (Table 6–4). Orbital vascular malformations fall into three categories: no flow, venous flow, and arterial flow. Assignment to each group is based on pertinent clinical and imaging criteria. Mixed forms with both no flow and venous components are grouped with the venous flow category.15

Figure 6–2. Continued. (Figure continued next page.)

Do Retrobulbar Tumors Cause Glaucoma?

Any orbital tumor that compresses the venous system may result in glaucoma secondary to backup in venous system drainage apparatus. Nordman et al reported 14 cases caused by a variety of tumors in 1961 (translation cited by Weinreb and Karwatowski4). This condition would generally be diagnosed with a computed tomography (CT) scan or an ultrasound. Intraocular tumors, such as ciliary body melanomas, may present with engorgement of the episcleral veins, which are called the “sentinel vessels.” However, these engorged

several reasons, including elevated EVP. Elevated EVP may result from the retrobulbar infiltration process.16 Jorgenson and Guthoff16 reported that 5 of 35 patients with endocrine orbitopathy had increased IOP in primary gaze. EVP was high, being between 16 and 23 mm Hg. It was speculated that compression of the ophthalmic veins by swollen extraocular muscles resulted in abnormal EVP and subsequently raised IOP. Also, the contraction of extraocular muscles resulted in the abnormal EVP and subsequently raised IOP. Also, the contraction of extraocular muscles may cause abnormally high IOPs in some specific directions of gaze. Usually fibrosis of the inferior rectus muscle significantly increases IOP in upgaze.4 The presence of exophthalmos with abnormal blood tests and either orbital ultrasound or CT scan of the orbit showing enlarged extraocular muscles will aid in the diagnosis of this condition.

Does Superior Vena Cava Syndrome (SVCS)

Cause Glaucoma?

Obstruction of the superior vena cava will result in increased venous pressure in those areas in which it provides venous drainage. These patients show edema and cyanosis of the face and neck as well as dilated vessels in the head, neck, chest, and upper extremities. Obstruction may increase the intracranial pressure, causing headaches, stupor, vertigo, seizures, and mental changes. Ocular findings include exophthalmos, papilledema, and prominent blood vessels in the conjunctiva, episclera, and retina.17 The IOP is usually elevated and is greater when the patient is in the supine position. It has been reported that glaucomatous cupping occurs infrequently with this syndrome, despite the elevated IOP. Some researchers propose that cupping does not occur because the IOP is counterbalanced by elevated intracranial pressure.17 Before the advent of antibiotics, this syndrome was commonly caused by mediastenitis secondary to the pulmonary infections of syphilis or tuberculosis. Presently, malignancy is the cause of 97% of these cases. Occasionally, aortic aneurysm, enlarged hilar nodes, and intrathoracic thyroid disease may be involved. Diagnosis is suggested by the clinical appearance of the face and neck, “pumpkin head” appearance, and by altered neurologic status accompanied by frequent complaints of headaches. The glaucoma is bilateral and usually gives rise to no subjective complaints. The site of obstruction may be demonstrated by venography or scintigraphy, but not without attendant hazards. These tests are generally not warranted. SVCS is usually more frequent on the right side, with a ratio of 4:1, and at present the most common cause is bronchogenic carcinoma.18

Does Congestive Heart Failure Lead to Glaucoma?

A report in the German-language literature by Bettelheim19 has demonstrated that elevated EVP in pulmonary hypertension can cause glaucoma and it was termed “cardiogenesis glaucoma.” No details are available, as the original article has not been translated into English. Nevertheless, this type of glaucoma points out that many case reports in the literature present intriguing diagnostic questions that remain unanswered. Another cardiac abnormality causing bilateral corkscrew episcleral veins occurred in a 56-year-old woman with an insidious onset of redness in both eyes, developing over a course of 6 months.20 She

118 Glaucoma Associated with Raised Episcleral Venous Pressure: The “Red Eye“ Glaucomas

had a history of rheumatic heart disease and had marked tricuspid valve incompetence. She did not have elevation of her IOP. The important concept in this article concerns the use of orbital color Doppler ultrasound to detect this unusual episodic biphasic blood flow present in both superior ophthalmic veins. Similar Doppler flow patterns were demonstrated on both of this patient’s internal jugular veins. Even though the patient was not in congestive heart failure at the time of her exam, it appears that the congestive effect in this patient was caused by tricuspid incompetence transmitting the ventricular pressure as reversed flow in the superior ophthalmic veins. Nevertheless, it was not a constant arterialized reversal of flow seen in a typical carotid cavernous sinus fistula. The noninvasive nature of color Doppler imaging and its ability to perform in an outpatient clinic makes it a choice over standard angiography in many situations.

Does Thrombosis of the Cavernous Sinus

or Superior Ophthalmic Vein Cause Glaucoma?

Occlusion or thrombosis of the superior ophthalmic vein or the cavernous sinus is a nonspecific finding that may be caused by such disorders as tumors of the skull base or nasopharynx. Sometimes no cause can be found. Brismar and Brismar21 described eight cases with increased EVP and glaucoma. Typically, these patients will have third, fourth, and sixth cranial nerve palsies. Retroorbital pain associated with ophthalmoplegia is typical, and more serious underlying causes need to be ruled out. Septic cavernous sinus thrombosis is not difficult to distinguish because of its fulminant nature. Many of these cases show spontaneous remission. Improvement with steroid therapy does not help in establishing the etiologic cause. Extensive clinical and radiologic evaluation should be done on these patients to discern a more serious underlying disorder. These tests would include carotid angiography, tomography of the skull base, and nasopharyngoscopy with blind biopsies. Orbital phlebography has a definite value in the diagnosis of these patients. Infrequently, it is quite a challenge to distinguish between Talosa-Hunt syndrome and aseptic cavernous sinus thrombosis. Although the IOP was normal in these eight cases, many of them had abnormalities of the optic nerve and visual field defects that had not been clearly described. Conjunctival venous dilations and retinal venous dilations were present in a number of these cases.

Does Vasculitis of the Episcleral and/or Orbital Veins Cause Glaucoma?

Patients with anterior scleritis may have elevated IOP related to raised EVP. In a German-language article by Jorgensen and Guthoff,16 64 patients were described with dilated vessels and glaucoma. Raised EVP was the cause of the elevated IOP. Jorgensen and Guthoff described cases of spontaneous carotid cavernous fistula, Sturge-Weber syndrome, orbital tumors, endocrine ophthalmopathy, anterior scleritis, and idiopathic cases. A variety of pathophysiologic mechanisms were involved. After systemic steroid therapy, both raised IOP and elevated EVP returned to normal.

Can Jugular Venous Obstruction Cause Glaucoma?

In 1946, Meyer22 described a type of secondary glaucoma due to inflammatory jugular phlebostenosis and called it “glaucoma exogenicum.” He traced clinically the cause of glaucoma to jugular phlebostenosis caused by proliferative endophlebitis. He claimed that the bulk of blood entering the head is drained off by the internal jugular veins on either side of the neck. A relatively small amount of venous blood passes through the external jugular veins, and another very small portion returns by way of the suboccipital plexus into vertebral and deep cervical veins and from there into the anominate veins. In Meyer’s era the primary cause of the jugular endophlebitis could be traced to oral infections, such as acute tonsillitis, and other pharyngeal infections. Meyer found that the application of leeches in the treatment of purulent phlebitis in the lower extremities was beneficial, and he stated that previously ophthalmologists had used leeches in glaucoma cases. They applied leeches over the temporal region in glaucoma patients and this application resulted in a temporary decongestion of the eye. He claimed that “recalibration” of the jugular veins with leeches in inflammatory obstruction brings on a total decongestion of the whole head area and therefore has a permanent therapeutic effect.

Does Inversion Therapy Lead to Glaucoma?

The IOP typically increases as the body assumes a more dependent posture. When the body is totally inverted in a vertical orientation, the IOP rapidly rises to a level approximately double the normal erect posture. Eleven patients had their EVP and gonioscopy performed in the supine and inverted positions.23 The IOP rose rapidly; within 10 seconds 70% of the increase had occurred and within 1 minute a constant value was reached. It was felt that the rapid rise in pressure was due to mechanical compression of the orbital contents against the globe, and that congestion and expansion of the uveal tissue from increased venous and arterial pressure within the orbit also played an important role. The investigators felt that the sustained increase in venous pressure in the orbit and additional contributions to the IOP may be due to a net increase in the rate of aqueous production. Alterations in the rate of uveoscleral outflow may also be a factor. They found that for every 0.83 mm Hg increase in EVP, there was a 1 mm Hg increase in IOP.

What Arteriovenous Anomalies May Lead to Glaucoma?

Various arteriovenous anomalies that may cause glaucoma are described below.

Does Carotid-Cavernous Sinus Fistula (CCSF)

Cause Glaucoma?

CCSF can be subdivided into (1) etiologic (i.e., spontaneous or traumatic), (2) hemodynamic, (i.e., high or low flow), and (3) anatomic (i.e., direct or dural). CCSFs provide a free communication between the internal carotid artery and the surrounding cavernous sinus resulting in high blood flow and high mean pressure in the shunt.3 A reversal of the blood flow in these vessels leads to conges-