Papilledema

For most family physicians, the complete physical examination of a patient includes direct ophthalmoscopic visualization of the optic nerve head and adjacent vessels through an undilated pupil. This view of the fundus, while limited in scope, can provide important information about the systemic health of a patient.

Although the term "papilledema" is sometimes used to denote any swelling or irregularity of the optic nerve head, the general terminology should be "optic disc swelling" or "optic disc edema." The term papilledema should be used only when swelling of the optic disc results from increased intracranial pressure. Optic disc edema may occur from many sources other than papilledema. Furthermore, swelling or elevation of the optic nerve head may occur without edema.

Family physicians should be able to carefully evaluate the optic discs. A delay in the diagnosis of true papilledema can be devastating. Conversely, overdiagnosis of papilledema may foster unnecessary, increased use of expensive neurodiagnostic tests such as computed tomographic (CT) scanning and magnetic resonance imaging. An understanding of optic disc conditions that masquerade as papilledema can help family physicians provide accurate diagnosis and appropriate consultation to patients with abnormal-appearing or elevated optic discs. Optic Nerve Anatomy

The optic nerve, which is composed of axons from retinal ganglion cells, is considered to be a sensory, or afferent, nerve fiber tract of the brain. The optic nerve head, or optic disc, is the clinically visible anterior extent of the optic nerve Figure 1). The optic disc measures approximately 1.5 mm horizontally and 1.75 mm vertically and has a central depression known as the physiologic cup.

Upon entering the optic nerve head, the axons of retinal ganglion cells become segregated into bundles by astrocytes. Before these axon bundles exit the eye, they pass through the fenestrated connective-tissue scaffolding of the sclera, known as the lamina cribrosa. Cytoplasmic transport, also referred to as axoplasmic flow, is responsible for maintaining structure, supplying synapse materials and clearing degradation products within each axon.

The meningeal covering of the brain (i.e., the dura mater, the arachnoid and the pia mater, including the subarachnoid space with cerebrospinal fluid) continues anteriorly in the orbit to surround the optic nerve. The central retinal artery, a branch of the ophthalmic artery, penetrates the meninges and the optic nerve within the orbit. The artery courses anteriorly through the optic nerve to enter the eye. Blood flows through the inner retina and then drains into the central retinal vein. The central retinal vein exits the eye and traverses the optic nerve to join the superior ophthalmic vein in the orbit. Papilledema

The normal contents of the rigid bony skull include brain tissue, blood and cerebrospinal fluid. An increase in the volume of any one of these substances without an appropriate compensatory decrease in other tissue volumes may cause increased intracranial pressure. The rapid addition of as little as 80 mL of any constituent substance can raise intracranial pressure to a level incompatible with life.(1)

Patients with papilledema usually have signs or symptoms of elevated intracranial pressure, such as headache, nausea, vomiting, diplopia, ataxia or altered consciousness. However, some patients with papilledema do not have lateralizing or localizing signs.(2)

Papilledema may be associated with transient obscurations of vision, described as periods of visual blackout lasting seconds to minutes. These visual disturbances occur with postural change or the Valsalva maneuver or, less commonly, at rest. Patients may have several episodes of transient visual loss each day. There appears to be no relationship between the frequency of transient visual obscurations and permanent visual loss.

Visual field defects in patients with papilledema include an increase in the size of the blind spot, possibly due to displacement of retinal photoreceptors, or an induced peripapillary hyperopia that causes refractive scotoma.(1,3) Arcuate scotomas may be present, particularly in the inferior nasal visual field. With longstanding papilledema, diffuse constriction of the visual field may occur. Loss of central vision, an infrequent manifestation of acute papilledema, may occur when fluid leakage from optic disc vessels extends into the macula. Other visual disorders include horizontal diplopia from stretching or compression of the abducent nerve and vertical diplopia from involvement of the trochlear nerve.

The stages of papilledema have not been standardized. Furthermore, the ophthalmoscopic appearance of the optic nerve head in papilledema is dynamic rather than static.(1,4) Increased intracranial pressure is transmitted to the retrolaminar region of the optic nerve; this results in obstruction of anterograde axoplasmic flow, distention of the axons anterior to the lamina cribrosa and swelling of the optic nerve head (Figure 2).

Congestion of optic nerve fibers as a result of axoplasmic flow stasis produces capillary dilatation and optic disc hyperemia early in the course of papilledema. Blurring of the optic disc margins from the accumulation of fluid within axonal fibers is also an early manifestation of papilledema. This sign can best be seen with the "red-free" filter (green light) on the direct ophthalmoscope. Another early sign of papilledema is mild optic disc swelling (Figure 3), which is best appreciated with stereoscopic instrumentation. Optic disc swelling is present initially at the vertical margins of the optic disc and later at the horizontal margins. Splinter hemorrhages also may occur.

With continued elevation of intracranial pressure, spontaneous venous pulsation will be absent. Unfortunately, spontaneous venous pulsation is also absent in approximately 20 percent of the normal population. The presence of spontaneous venous pulsation militates against concurrent increased intracranial pressure.

These signs are not pathognomonic for papilledema. However, papilledema should be suspected when several of these signs are present.

As optic disc elevation becomes more pronounced, the optic disc margins become increasingly blurred from stretching of the peripapillary nerve fiber layer. Increased optic disc edema from axoplasmic flow stasis causes venous congestion and retinal venous tortuosity, further enlargement of optic disc capillaries and or nasal visual field. With longstanding papilledema, diffuse constriction of the visual field may occur. Loss of central vision, an infrequent manifestation of acute papilledema, may occur when fluid leakage from optic disc vessels extends into the macula. Other visual disorders include horizontal diplopia from stretching or compression of the abducent nerve and vertical diplopia from involvement of the trochlear nerve.

The stages of papilledema have not been standardized. Furthermore, the ophthalmoscopic appearance of the optic nerve head in papilledema is dynamic rather than static.(1,4) Increased intracranial pressure is transmitted to the retrolaminar region of the optic nerve; this results in obstruction of anterograde axoplasmic flow, distention of the axons anterior to the lamina cribrosa and swelling of the optic nerve head (Figure 2).

Congestion of optic nerve fibers as a result of axoplasmic flow stasis produces capillary dilatation and optic disc hyperemia early in the course of papilledema. Blurring of the optic disc margins from the accumulation of fluid within axonal fibers is also an early manifestation of papilledema. This sign can best be seen with the "red-free" filter (green light) on the direct ophthalmoscope. Another early sign of papilledema is mild optic disc swelling (Figure 3), which is best appreciated with stereoscopic instrumentation. Optic disc swelling is present initially at the vertical margins of the optic disc and later at the horizontal margins. Splinter hemorrhages also may occur.

With continued elevation of intracranial pressure, spontaneous venous pulsation will be absent. Unfortunately, spontaneous venous pulsation is also absent in approximately 20 percent of the normal population. The presence of spontaneous venous pulsation militates against concurrent increased intracranial pressure.

These signs are not pathognomonic for papilledema. However, papilledema should be suspected when several of these signs are present.

As optic disc elevation becomes more pronounced, the optic disc margins become increasingly blurred from stretching of the peripapillary nerve fiber layer. Increased optic disc edema from axoplasmic flow stasis causes venous congestion and retinal venous tortuosity, further enlargement of optic disc capillaries and the development of flame-shaped hemorrhages. The vessels at the edge of the optic disc become obscured by the increasingly opaque nerve fiber layer. Retinal infarcts (cotton-wool spots) or lipoproteinaceous accumulations (hard exudates) may be seen near the optic disc or in the macular area (Figures 4 and 5).

It is not uncommon for the landmarks of the optic nerve head to become unrecognizable because of extensive swelling, hemorrhage, venous tortuosity and obscuration, and nerve fiber layer infarct (Figure 5). The optic disc cup may be absent at this stage.

When papilledema eventually subsides due to resolution of the increased intracranial pressure or loss of optic nerve fibers, there may be varying degrees of optic atrophy, depending on the severity and duration of the papilledema. Ophthalmoscopically, the atrophic optic disc is no longer a normal pink color, but is pale yellow to bone white (Figure 6). Sometimes the surface of the optic disc has a milky-gray sheen. Atrophic enlargement of the physiologic optic nerve cup may be noted. The caliber of the optic disc vessels generally appears to be decreased, and vascular sheathing may be present. Causes of Papilledema

Increased intracranial pressure and papilledema are observed with several conditions, including intracranial tumors, idiopathic intracranial hypertension (pseudotumor cerebri), shunt obstruction, subarachnoid hemorrhage, subdural hematoma and intracranial inflammation (Table 1). Papilledema resulting from an intracranial tumor is dependent on the location of the tumor and its rate of growth. Infratentorial tumors often disrupt the flow of cerebrospinal fluid through the cerebral aqueduct; consequently, these tumors are more likely than supratentorial tumors to be associated with papilledema. Slowly progressive tumors produce papilledema more often than rapidly growing tumors.

The incidence of idiopathic intracranial hypertension, or pseudotumor cerebri (once called benign intracranial hypertension), is only one per 100, 000 in the general population, but is 19 per 100,000 among obese women of childbearing age.(5-7) Uncontrolled idiopathic intracranial hypertension can lead to blindness.

The diagnosis of idiopathic intracranial hypertension is based on the following criteria: (1) the presence of papilledema; (2) normal or small ventricles, as demonstrated by neuroradiologic imaging studies, and (3) increased intracranial pressure and normal cerebrospinal fluid composition, as documented by lumbar puncture. In some cases, a search for the cause of idiopathic intracranial hypertension has led to the diagnosis of intracranial venous drainage impairment (dural sinus thrombosis, cavernous sinus thrombosis, jugular vein ligation), endocrine or metabolic changes and disorders (menarche, pregnancy, hypoparathyroidism, Addison's disease, Turner's syndrome), medication use (corticosteroids, oral contraceptives, antibiotics, vitamin A) and systemic illness (iron deficiency anemia, blood dyscrasias, encephalopathy, respiratory insufficiency, Whipple's disease). Differential Diagnosis of Papilledema

Several conditions that cause or mimic optic disc swelling should be differentiated from papilledema (Table 2). REFRACTIVE ERROR

In a patient with marked hyperopia, the optic disc looks large and may appear swollen. This is an illusion created by reduced globe diameter and the optical properties of the lens.(1) All other signs of papilledema are absent. CONGENITAL STRUCTURAL ANOMALIES

Congenital structural anomalies of the optic disc may be identified by variable dysplastic organization of the vessels, neural tissues and supporting structures of the optic disc(l,8,9) (Figure 7). Patients with these anomalies may have basal encephaloceles and a characteristic appearance that includes short stature, hypertelorism, flattened nasal bridge and a cleft lip or palate.

Optic disc hypoplasia is characterized by a small optic disc surrounded by a yellowish peripapillary halo, termed a "double ring" (Figure 8). The outer ring represents the junction of the sclera and the lamina cribrosa, while the inner ring represents the termination of the retina and the retinal pigment epithelium. Endocrinologic dysfunction is commonly associated with this condition.

Myelination of the nerve fibers generally ceases at the lamina cribrosa. Occasionally, intraocular myelination produces blurring of the disc margins by flameshaped aggregations of white myelinated nerve fibers(l,10)(Figure 9). A tilted disc occurs from oblique insertion of the optic nerve in the globe, which results in an oval-appearing optic disc, typically with elevation of the supratemporal optic disc and depression of the inferonasal optic disc. Patients who are myopic may also have tilted discs (Figure 10). These conditions may be distinguished from papilledema by a lack of the systemic symptoms that occur with papilledema, the static nature of the findings and the lack of vascular engorgement or hemorrhage. OPTIC DISC DRUSEN

Optic disc drusen may be completely or partially buried in the optic nerve head, causing optic disc elevation that may be difficult to distinguish from true papilledema(8,9,11-13) Figure 11). When present on the optic disc surface, drusen impart a glistening, focal, irregular, nodular appearance. Drusen may be associated with branch retinal vein occlusions, retinal hemorrhages, disc margin blurring and partial visual field JOSS.14-16 Drusen are thought to represent coalescent calcified extracellular mitochondria from aberrant axoplasmic flow. OPTIC DISC TUMORS AND INFILTRATIVE INFLAMMATORY DISORDERS

Primary optic disc tumors may appear similar to large drusen.(1,17 ) Astrocytic hamartomas (Figure 12) and gliomas are slightly more gray, pink, yellow or white than the surrounding normal disc tissue. These tumors may be associated with tuberous sclerosis or neurofibromatosis. Capillary hemangiomas appear as circular, reddish masses that are slightly elevated (Figure 13), while cavemous hemangiomas are large dilated veins that look like clusters of grapes. Capillary hemangiomas may be associated with von Hippel-Lindau disease. Melanocytomas are dark-black, benign intraocular tumors and are usually found in a juxtapapillary position(18)(Figure 14).

Secondary optic disc infiltration from sarcoidosis (Figure 15), leukemia or metastatic tumors such as malignant melanoma is variable in appearance and can cause blurring of the disc margins and optic atrophy.(1,17) Optic disc infiltration from inflammatory disorders and tumors may occur simultaneously with true papilledema. However, the optic nerve head in an infiltrative process is usually less diffusely hyperemic in color and shows evidence of fluffy, grayish-yellow material obscuring the margins of the optic disc. VASCULAR OCCLUSIONS

Occlusion of the central retinal artery is classically associated with a cherry red spot in the macula, an opaque retina from retinal ischemia and edema, vascular attenuation, optic disc pallor and variable blurring of the optic disc margin (Figure 16). Occlusion of the central retinal vein is usually characterized by marked venous engorgement, extensive retinal hemorrhages, blurring of the optic disc margin and the presence of a soft-yellow exudate(19) (Figure 17). Features that distinguish central retinal artery or vein occlusion from papilledema include the lack of systemic symptoms, the unilaterality of findings and the profound loss of vision.

Anterior ischemic optic neuropathy, which results from infarction of the optic disc, usually presents with sudden, profound loss of vision (Figure 18). In this disorder, segments of the optic disc appear pale and edematous.(20) Anterior ischemic optic neuropathy from temporal arteritis may be associated with bilateral visual loss in over two-thirds of patients. OPTIC DISC NEOVASCULARIZATION

Neovascularization of the optic disc occurs as the result of various ischemic conditions, particularly proliferative diabetic retinopathy and central retinal vein occlusion.(19,21) Ophthalmoscopically, the optic disc is hyperemic, and neovascularization blurs the optic disc margins (Figure 19). These fragile vessels may rupture, causing vitreous preretinal or intraretinal hemorrhage, fibrotic tractional retinal detachment or neovascular glaucoma. OPTIC NEURITIS

Optic neuritis is an inflammation of the optic disc.(1) The condition can be anterior, with visible optic nerve head changes, or retrobulbar, without visible evidence on ophthalmoscopic examination. The ophthalmoscopic appearance of anterior optic neuritis (papillitis) may be indistinguishable from papilledema. However, unlike patients presenting with papilledema, patients with optic neuritis usually present with sudden loss of central vision and pain on attempted eye movement. COMPRESSIVE OPTIC NEUROPATHY

Compression of the optic nerve from an expanding orbital mass, such as an orbital tumor, pseudotumor of the orbit or acute orbital hemorrhage, may produce optic disc edema and visual loss. Thyroid-related orbitopathy results from autoimmune-mediated lymphocytic infiltration of the extraocular muscles and orbital fat.(22)

Compression of the optic nerve, particularly at the apex of the bony orbit, can produce ophthalmoscopic findings similar to those in papilledema. Conditions causing optic nerve compression can be differentiated from papilledema by the clinical history, signs of orbital congestion (e.g., proptosis, increased resistance to retrodisplacement of the globe, periorbital edema) and an orbital CT scan showing extraocular muscle enlargement or an orbital mass. The preparation of this article was supported in part by an unrestricted grant to the University of Missouri-Columbia from Research to Prevent Blindness, New York, N. Y REFERENCES

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