Fig. 18-17  Choroidal melanoma invading the ciliary body and angle.

are presented in Chapter 19, the discussion here is limited to tumors in adults.

Malignant melanoma can be associated with normal, elevated, or depressed IOP. Elevated IOP is reported more frequently with melanomas of the anterior uveal tract than with choroidal melanomas.442 Glaucoma can occur through several mechanisms, including the following: (1) direct extension of the tumor into the trabecular meshwork (Fig. 18-17); (2) seeding of tumor cells into the outflow channels; (3) pigment dispersion; (4) inflammation; (5) hemorrhage, inducing hemolytic glaucoma, and suprachoroidal hemorrhage, leading to angle closure; (6) neovascularization of the angle; (7) angle closure from anterior displacement of the lens–iris diaphragm, peripheral anterior synechiae, or posterior synechiae, and (8) obstruction of the trabecular meshwork by macrophages containing melanin released by a necrotic tumor (melanomalytic glaucoma).

Most eyes with advanced melanomas are treated with enucleation or radiation.443–449 In some cases, local excisional surgery may be a viable option.450,451 If the eye is retained, medical therapy is used to

attempt to control IOP. Unfortunately many irradiated eyes develop neovascular glaucoma. In a 5-year study of helium ion irradiation, for example, Decker and co-workers found that 43% of patients developed neovascularization.445 Neovascular glaucoma was often not responsive to treatment and was a prominent contributing factor in the subsequent decision to perform enucleation. Metastatic tumors to the eye may cause glaucoma, especially if the metastasis involves the anterior segment.452–454 The mechanisms producing glaucoma are similar to those described for malignant melanoma. There is one report of a metastatic tumor invading Schlemm’s canal and the collector channels.455 Many metastatic tumors are treated with radiation and/or chemotherapy. Medical treatment for glaucoma is indicated to retain vision and reduce discomfort.

Intraocular lymphoma and leukemia can produce glaucoma by seeding the outflow channels or by producing angle closure.454 Several benign ocular tumors can also produce glaucoma. Melanocytomas of the iris can invade the angle456 or cause sufficient pigment dispersion to obstruct the trabecular meshwork.454

Pigment dispersion and glaucoma are also reported with adenomas of the pigment epithelium,344,457 melanosis oculi,458 and nevus of Ota.459–461 These conditions generally respond well to medical

therapy or to ALT. Medulloepithelioma can displace the lens–iris diaphragm or produce neovascularization of the angle.442

Amyloidosis

The hereditary systemic amyloidoses are a group of diseases in which amyloid is deposited in tissues throughout the body, leading to cardiovascular, renal, endocrine, muscular, gastrointestinal, and neurologic deficits.The ocular findings include vitreous opacification, proptosis, lid abnormalities, extraocular muscle weakness, ­anisocoria, internal ophthalmoplegia, and retinal vasculitis.462,463

Secondary open-angle glaucoma develops in approximately 25% of the patients with the hereditary systemic amyloidoses.The glaucoma somewhat resembles pigmentary glaucoma because modest pigment exists in the trabecular meshwork and on the corneal endothelium. There is also a resemblance to the exfoliation syndrome because white flecks are seen on the iris near the pupil and on the anterior lens capsule.464 Histologic examination of these eyes reveals heavy accumulation of amyloid in the trabecular meshwork.463 Anatomic changes and amyloid deposition involve the ciliary body as well.465 This accumulation most likely causes glaucoma by obstructing aqueous humor outflow.466 Glaucoma can also be caused by elevated episcleral venous pressure.467

Another form of familial systemic amyloidosis and secondary open-angle glaucoma has been reported that includes lattice dystrophy of the cornea, cranial neuropathy, and no vitreous opacities.468 These patients may require multiple penetrating keratoplasties over the years, and unresponsive glaucoma is a frequent sequela.469 There is also a report of non-familial systemic amyloidosis associated with secondary open-angle glaucoma.470

The treatment of glaucoma in amyloidosis is similar to the treatment of POAG.467 It has been reported that filtering surgery is successful initially but that the blebs fail over several months to a few years because of the accumulation of amyloid material.471

Elevated episcleral venous pressure

Any condition that raises episcleral venous pressure also raises IOP by obstructing the post-trabecular flow of aqueous humor. In acute experiments, when a pressure cuff is placed around a patient’s neck

and episcleral venous pressure is raised 1 mmHg, IOP increases approximately 0.8 mmHg.472,473 In a study of IOP and episceral

venous pressure in patients who were placed in a vertically inverted posture (i.e., upside down), Friberg and co-workers found that when the episcleral venous pressure increased 0.83 0.21 mmHg, the IOP rose 1 mmHg.474 The difference between these pressure increases has been attributed to fluid being forced from the eye475 or to pseudofacility (i.e., a pressure-related reduction in aqueous humor formation).473 Recently, however, the concept of pseudofacility has been questioned. It is difficult to interpret acute experiments such as the one just described because IOP, outflow facility, and episcleral venous pressure never reach steady state.Animal models can measure episcleral venous pressure and IOP changes reproducibly in acute experimental settings,476,477 but these findings do not necessarily mimic the clinical situation of chronically elevated episcleral venous pressure in the human. For example, acute elevations of episcleral venous pressure increase the total outflow facility,475 whereas chronic ­elevations often decrease outflow facility.478 Thus it is difficult to

predict accurately the change in IOP that will accompany a specific rise in episcleral venous pressure.The two pressure changes are often of similar magnitude, but the IOP may be less than or even greater than the rise in episcleral venous pressure.479

The physical signs of elevated episcleral venous pressure depend on the underlying disease or condition and include chemosis, proptosis, orbital bruit, and pulsating exophthalmos. Generally the episcleral veins are dilated, tortuous, and have a corkscrew appearance, although this can vary from mild to severe.480 The retinal veins are usually not dilated because the rise in venous pressure is counterbalanced by a rise in IOP. The angles are open, and blood is often present in Schlemm’s canal.The elevated IOP may produce typical glaucomatous optic nerve cupping and visual field loss. Outflow facility is normal in most cases of elevated episcleral venous pressure. In longstanding cases, however, secondary changes in the trabecular meshwork may reduce outflow facility.478

Elevated episcleral venous pressure can be confused with any condition that produces dilated extraocular vessels, including conjunctivitis, episcleritis, scleritis, and general orbital inflammation. Usually the venous pressure is normal in these inflammatory conditions. Furthermore, the most common of these entities, conjunctivitis, affects the superficial vessels and spares the deeper episcleral vessels. This distinction can be made by observing the vessels during slitlamp examination while moving the conjunctiva with a moist swab. In addition, dilated superficial vessels constrict in response to topical agents such as phenylephrine 2.5%, whereas deeper vessels do not.

Many conditions can produce elevated episcleral venous pressure. These conditions are usually divided into three major categories: obstruction of venous drainage, arteriovenous fistulas, and idiopathic elevations (Box 18-3). The discussion here is restricted to the more common entities.

Superior Vena Cava Obstructions

Various conditions can obstruct the superior vena cava, including

tumors, aortic aneurysms, mediastinal masses, hilar adenopathy, and intrathoracic goiter.481–483 This obstruction produces edema and

Box 18-3  Etiology of elevated episcleral venous pressure

I.Obstruction of venous drainage

A.Episcleral

1.Chemical burns

2.Radiation

B.Orbital

1.Retrobulbar tumors

2.Thyroid eye disease

3.Pseudotumor

4.Phlebitis

C.Cavernous sinus thrombosis

D.Jugular vein obstruction

E.Superior vena cava obstruction

F.Pulmonary venous obstruction II. Arteriovenous fistulas

A.Orbital

B.Intracranial

1.Carotid-cavernous fistula

2.Dural fistula

3.Venous varix

4.Sturge-Weber syndrome III. Idiopathic

cyanosis of the face and neck (pumpkinhead appearance) as well as dilated vessels in the head, neck, chest, and upper extremities.484 Obstruction of the superior vena cava increases intracranial pressure, which leads to headache, stupor, vertigo, seizures, and mental changes. The associated ocular findings include exophthalmos, papilledema, and prominent blood vessels in the conjunctiva, episclera, and retina. Intraocular pressure is elevated, and the IOP increase is greater when the patient is in the supine position.485 There is a clinical impression that glaucomatous cupping occurs infrequently with superior vena cava obstruction despite the elevated IOP. Some researchers propose that cupping does not occur because the IOP is counterbalanced by elevated intracranial pressure.486 Therapy in this situation is directed toward relieving the obstruction.487 During this period, the IOP elevation is treated primarily with medications that decrease aqueous production, such as -blockers and topical or systemic CAIs; agonists may also be helpful.

Thyroid Eye Disease

Thyroid eye disease is known by a variety of names, including endocrine exophthalmos, thyrotropic exophthalmos, and Graves’ disease. The hormonal defect of this condition is unclear, and patients can

be hypothyroid, euthyroid, or hyperthyroid when their eye problems begin.488,489 The physical findings are variable and include exophthal-

mos, chemosis, lid retraction, lid lag, a staring or startled appearance, dilated conjunctival and episcleral vessels, corneal exposure, restriction of ocular motility, optic atrophy, and diminished retropulsion of the globe.490 Intraocular pressure can be increased for several reasons, including elevated episcleral venous pressure. Ocular rigidity is reduced in thyroid eye disease, and thus IOP measurements should be taken with applanation rather than Schiøtz tonometry. In addition, because of restricted ocular motility, pressure measurements should be taken with the patient gazing down slightly to minimize a potential transient IOP rise.491

Ocular hypertension and open-angle glaucoma occur relatively frequently in thyroid-related immune orbitopathy with a prevalence of 8.5% and 2.5% respectively in one study – a prevalence which is significantly higher than controls.492 In another study, the prevalence of glaucoma was as high as 14%.493

When glaucoma occurs in the setting of thyroid eye disease, elevated IOP is treated with topical aqueous humor suppressants; topical prostaglandins and agonists may also be useful. Corticosteroids, radiation, and surgical decompression have been

employed to protect the optic nerve, limit corneal exposure, and improve cosmetic appearance.494–500 In addition to thyroid eye

disease, in which signs and symptoms of thyroid disease (usually hyperthyroidism) have direct ocular manifestations, long-term study indicates an association between open-angle glaucoma and a history of treatment for thyroid disease, including hypothyroidism.501

Arteriovenous Fistulas

Carotid-cavernous fistulas 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.502 The reversal of blood flow in the vessels leads to congestion of the orbital veins and soft tissues.The shunting of the blood may produce ocular ischemia503 and may transmit arterial pulsa-

tions to the globe. Patients with carotid-cavernous fistulas often give a history of previous trauma.504,505 Many of these patients have

Fig. 18-18  Carotid-cavernous fistula.

(Courtesy of Randall T Higashida, MD, UCSF Medical Center, San Francisco.)

a dramatic appearance, with pulsating exophthalmos, chemosis,

lid edema, vascular engorgement, and restriction of ocular motility (Fig. 18-18).506,507 The conjunctival and episcleral veins have a

tortuous, corkscrew appearance.480 The physical findings usually occur on the same side as the fistula. Because of the connec-

tions between the cavernous sinuses, however, the findings may be bilateral or even alternating.508,509 Patients with carotid-cavern-

ous fistula often complain of a noise in their head or ears; a bruit is often present over the frontal or temporal regions or over the globe. Intraocular pressure is elevated in the majority of patients

because of increased episcleral venous pressure, although angleclosure and neovascular glaucoma have also been reported.510–512

Skull and orbital radiography, ultrasonography, and CT or magnetic resonance imaging (MRI) confirm the diagnosis, but arteriography provides the most detailed information about the fistula.508 Treatment of these fistulas can be difficult and is usually reserved for individuals who have severe pain, incapacitating bruit, progressive glaucomatous visual loss, or other serious complications. A variety of embolization and balloon catheter techniques have been employed with increasing success.513–518

Dural fistulas are communications between the cavernous sinus and an extradural branch of the external or internal carotid artery.These fistulas generally have lower blood flow and lower mean pressure.519– 522 The clinical appearance of these patients is far less dramatic than that of patients with carotid-cavernous fistulas (Fig. 18-19). Patients with dural fistulas lack bruits and have variable exophthalmos and variable limitation of ocular motility. The conjunctival and episcleral vessels have the same corkscrew, arterialized appearance, and IOP is elevated.This condition is often seen in elderly women who have no history of trauma.523 At times, the findings are so subtle that only the dilated vessels distinguish this entity from POAG.This condition has been referred to as the ‘red-eyed shunt syndrome’ by Phelps and coworkers.522 Low-flow or dural fistulas can close spontaneously and may not require treatment. High-flow shunts respond well to interventional approaches in experienced hands.516 Elevated IOP generally responds to topical -adrenergic antagonists and CAIs. Although sometimes effective, topical prostaglandins and -adrenergic agonists often exacerbate the hyperemia associated with the fistula. Choroidal effusion has been reported associated with topical prostaglandin use in a patient with elevated episcleral venous pressure.523 Glaucoma associated with neovascularization may respond to local laser treatment.524

Fig. 18-19  Dural shunt with engorged vessels.

Sturge-Weber Syndrome

Sturge-Weber syndrome is a rare oculocutaneous disorder that produces increased IOP through a variety of mechanisms, including

elevated episcleral venous pressure and, possibly, maldevelopment of the chamber angle.525–530 Glaucoma that is often resistant to med-

ical therapy occurs in about 40% of patients with the syndrome. Often the glaucoma in these children (and adults) is very challenging to manage.531 This condition is discussed in Chapter 19.

Idiopathic Elevations

Several cases of unexplained or idiopathic elevations of episcleral venous pressure and IOP have been described.411,532–537 This con-

dition can be unilateral or bilateral and sporadic or familial. The IOP elevations can lead to glaucomatous cupping and visual field loss. The treatment of elevated episcleral venous pressure depends greatly on the underlying condition. Elevated IOP is treated with topical and systemic medications to reduce aqueous production.

Cholinergic agents may be useful, especially in patients with reduced outflow facility. Argon laser trabeculoplasty may also be helpful in these patients. One study reports lowering IOP with the topical administration of vasodilators.538

Many of these patients eventually require filtering surgery, but ophthalmologists must be aware of the increased possibility of complications. The high venous pressure favors the development

of intraoperative choroidal effusion, expulsive hemorrhage, and flat anterior chamber.534,539,540 It is recommended that prophylac-

tic sclerotomies be made in one or two inferior quadrants at the beginning of filtering surgery. The sclerotomies are then left open at the end of surgery and covered only by conjunctiva to allow continued drainage of suprachoroidal fluid.539

Staged trabeculectomy is another alternative which is intended to reduce the risks of surgical complications by decompressing the eye more gradually.541