Papilledema

Background
Papilledema is an optic disc swelling that is secondary to elevated intracranial pressure.[1, 2] In contrast to other causes of optic disc swelling, vision usually is well preserved with acute papilledema. Papilledema almost always presents as a bilateral phenomenon and may develop over hours to weeks. The term, as a matter of definition, is incorrect to be used to describe optic disc swelling with underlying optic nerve infectious, infiltrative, or inflammatory etiologies; but, it is correctly used if the underlying cause of elevated intracranial pressure is infectious, infiltrative, or inflammatory.

Pathophysiology
The disc swelling in papilledema is the result of axoplasmic flow stasis with intra-axonal edema in the area of the optic disc.[3] The subarachnoid space of the brain is continuous with the optic nerve sheath. Hence, as the cerebrospinal fluid (CSF) pressure increases, the pressure is transmitted to the optic nerve, and the optic nerve sheath acts as a tourniquet to impede axoplasmic transport. This leads to a buildup of material at the level of the lamina cribrosa, resulting in the characteristic swelling of the nerve head. Papilledema may be absent in cases of prior optic atrophy. In these cases, the absence of papilledema is most likely secondary to a decrease in the number of physiologically active nerve fibers.

Epidemiology
Frequency United States Rare International Rare Mortality/Morbidity Early detection and identification of cause may be life saving. Race No racial predilection exists. Sex Papilledema affects both sexes equally.

Age Papilledema can present at any age, though, during infancy, before the fontanelles close, the finding of papilledema may fail to occur despite elevated intracranial pressure. Proceed to Clinical Presentation

History
Most symptoms in a patient with papilledema are secondary to the underlying elevation in intracranial pressure.[3, 4] Headache: Increased intracranial pressure headaches are characteristically worse on awakening, and they are exacerbated by coughing or other type of Valsalva maneuver. Nausea and vomiting: If the rise in intracranial pressure is severe, nausea and vomiting may occur. This eventually may be followed by a loss of consciousness, pupillary dilation, and death. Pulsatile tinnitus Visual symptoms often are absent, but the following symptoms can occur: Some patients experience transient visual obscurations (graying-out of their vision, usually both eyes, especially when rising from a lying or sitting position, or transient flickering as if rapidly toggling a light switch). Blurring of vision, constriction of the visual field, and decreased color perception may occur. Diplopia may be seen occasionally if a sixth nerve palsy is associated. Visual acuity may be well-preserved, except in very advanced disease. Papilledema is sometimes found at routine examination in an asymptomatic individual. Inquire about potential causative medications.

Physical
The history should be taken, and a physical examination, including vital signs, should be performed. In particular, check the blood pressure to exclude malignant hypertension. The patient should be evaluated for neurologic problems and febrile illness. Visual acuity, color vision, and pupillary examination findings should be normal. A relative afferent pupillary defect is usually absent. Since an abduction deficit secondary to a false-localizing sixth nerve palsy sometimes may be seen in association with increased intracranial pressure, check cover test in cardinal fields of gaze and check for full motility. Careful dilated fundus examination should be performed to look for

the following signs: Early manifestations Disc hyperemia Subtle edema of the nerve fiber layer can be identified with careful slit lamp biomicroscopy and direct ophthalmoscopy. This most often begins in the area of the nasal disc. A key finding occurs as the nerve fiber layer edema begins to obscure the fine peripapillary vessels. Small hemorrhages of the nerve fiber layer are detected most easily with the red-free (green) light. Spontaneous venous pulsations that are normally present in 80% of individuals may be obliterated when the intracranial pressure rises above 200 mm water. Therefore, though the presence of spontaneous venous pulsations is very useful to exclude papilledema (except in cases of highly variable intracranial pressure), its absence is not very helpful. Late manifestations As the papilledema continues to worsen, the nerve fiber layer swelling eventually obscures the normal disc margins and the disc becomes grossly elevated. Venous congestion develops, and peripapillary hemorrhages become more obvious, along with exudates and cotton-wool spots. The peripapillary sensory retina may develop concentric or, occasionally, radial folds known as Paton lines. Choroidal folds also may be seen. Chronic manifestations If the papilledema persists for months, the disc hyperemia slowly subsides, giving way to a gray or pale disc that loses its central cup. With time, the disc may develop small glistening crystalline deposits (disc pseudodrusen).

Causes
Any tumors or space-occupying lesions of the CNS Idiopathic intracranial hypertension (also known as pseudotumor cerebri)[5] Decreased CSF resorption (eg, venous sinus thrombosis, inflammatory processes, meningitis, subarachnoid hemorrhage) Increased CSF production (tumors) Obstruction of the ventricular system Cerebral edema/encephalitis Craniosynostosis Medications, for example, tetracycline, minocycline, lithium, Accutane, nalidixic acid, and corticosteroids (both use and withdrawal)

Proceed to Differential DiaDifferential Diagnoses Central Retinal Vein Occlusion Hypertension Idiopathic Intracranial Hypertension Optic Neuritis, Adult Optic Neuropathy, Anterior Ischemic Optic Neuropathy, Compressive Pseudopapilledema Sarcoidosis Scleritis Thyroid Ophthalmopathy Toxic/Nutritional Optic Neuropathy Toxoplasmosis Uveitis, Classification Vogt-Koyanagi-Harada DiseaseLaboratory Studies Blood tests usually do not contribute to the diagnosis of papilledema. If the diagnosis is in doubt, CBC count, blood sugar, angiotensinconverting enzyme, erythrocyte sedimentation rate, and syphilis serology may be helpful to look for signs of infectious, metabolic, or inflammatory diseases.

Imaging Studies
Urgent neuroimaging (eg, CT scan, MRI) of the brain with contrast should be performed in an attempt to identify a CNS mass lesion. Consider magnetic resonance (MR) venography to detect venous sinus thrombosis. B-scan ultrasonography may be useful to rule out buried disc drusen. Fluorescein angiography can be used to help establish the diagnosis. Acute papilledema exhibits increased dilation of the peripapillary capillaries with late leakage of the dye. Autofluorescence may reveal disc drusen.

Other Tests
Perimetry Visual fields should be tested. They commonly show enlargement of the blind spot. With extreme disc edema, a pseudobitemporal hemianopsia may be seen. With chronic papilledema, constriction of the visual field, especially inferiorly, gradually can occur, which eventually may progress to a loss of central acuity and total blindness. Stereo color photographs of the optic discs are useful to document changes.

Procedures

A lumbar puncture should be performed following a normal MRI to assess the opening pressure of the CSF and to obtain CSF for analysis to rule out neoplastic and infectious etiologies. It may provide some therapeutic benefit, as the CSF pressure is reduced temporarily. Proceed to Treatment & Management

Medical Care

Therapy, whether medical or surgical, is tailored to the underlying pathological process and the progression of the ocular findings. Specific therapy should be directed to the underlying mass lesion if present. Diuretics: The carbonic anhydrase inhibitor, acetazolamide (Diamox), may be useful in selected cases, especially cases of idiopathic intracranial hypertension. (In the presence of venous sinus thrombosis, diuretics are contraindicated. In this scenario, evaluation by a hematologist is recommended.) Weight reduction is recommended in cases of idiopathic intracranial hypertension and can be curative.[7] Bariatric surgery may be considered in cases refractory to conventional methods of weight loss.
[8]

Corticosteroids may be effective in cases associated with inflammatory disorders (eg, sarcoidosis). Consider withdrawing causative medications, as weighed against other medical necessities and alternatives.

Surgical Care
The underlying mass lesion, if present, should be removed. Lumboperitoneal shunt or ventriculoperitoneal shunt can be used to bypass CSF. Optic nerve sheath decompression can be used to relieve worsening ocular symptoms in cases of medically uncontrolled idiopathic intracranial hypertension. This procedure probably will not ameliorate persistent headaches if present.

Consultations
Besides an ophthalmologist, a neurologist should be involved in monitoring the patient, and a neurosurgeon may be needed to help evaluate any underlying mass or to perform a shunting procedure.

Diet
Dietary restrictions and consultation with a dietitian in case of idiopathic intracranial hypertension is recommended. Proceed to M

Medication Summary
Diuretics may be helpful in cases of elevated intracranial pressure. Diamox and other carbonic anhydrase inhibitors can decrease the production of CSF.

Carbonic anhydrase inhibitors

Class Summary Can be used in selected cases because they decrease the production of CSF and, thus, lower intracranial pressure.
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Acetazolamide (Diamox, Diamox Sequels) The conversion of carbon dioxide to bicarbonate plays a key role in the production of both aqueous humor and CSF. Carbonic anhydrase inhibitors act by inhibiting the conversion of carbon dioxide to bicarbonate, thus inhibiting the production of both aqueous humor and CSF. Dosage should be individualized; most patients cannot tolerate more than 1 g/d because of the adverse effects (eg, dizziness, metallic taste, lethargy, paresthesias). Diamox sequels may be better tolerated than tablets.

Corticosteroids
Class Summary May be useful in cases where inflammatory lesions lead to a secondary elevation in CSF pressure. These drugs are effective in these cases because of their potent anti-inflammatory effects.
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Prednisone (Deltasone) Prednisone, like other corticosteroids, can cause profound and varied metabolic and immunologic effects. Its usefulness in these cases stems from its strong anti-inflammatory properties. Proceed to Follow-up

Further Outpatient Care

The patient should be examined weekly until stabilization of the ocular findings occurs. Well-developed papilledema takes 6-10 weeks to regress, following lowering of intracranial pressure.

Inpatient & Outpatient Medications

See Medication.

Complications
Unrelenting papilledema may eventually lead to permanent blindness.

Prognosis
The visual prognosis is generally good if the intracranial pressure is controlled.

Background
While papilledema is disc edema secondary to increased intracranial pressure, pseudopapilledema is apparent optic disc swelling that simulates some features of papilledema but is secondary to an underlying, usually benign, process. Most patients with pseudopapilledema lack visual symptoms, not unlike patients with true papilledema. In pseudopapilledema, no obscuration of the peripapillary vessels by the nerve fiber layer edema occurs. Pseudopapilledema may be unilateral or bilateral, but almost all cases of papilledema are bilateral. An extensive workup is usually unnecessary, and an experienced general ophthalmologist or neuro-ophthalmologist can correctly diagnose pseudopapilledema via an ophthalmoscopic examination.

Pathophysiology
There are a multitude of causes of true disc swelling and other disorders that may mimic disc swelling, some of which represent a morphologic variant of normal. The optic nerve may be elevated, simply because the optic nerve enters the eye at an extremely oblique angle (tilted disc), giving a portion a more elevated aspect (usually nasally). The optic cup may be smaller than usual in a hyperopic eye. This causes crowding of the axons, which become heaped-up and elevated as they leave the eye. The nerve fiber layer, which is normally translucent, may be partially myelinated. This can lead to the appearance of a large cup with blurring of the disc margins. A subtler (but common) cause of pseudopapilledema is buried disc drusen. This article focuses primarily on optic disc drusen. Disc drusen are composed of small conglomerates of mucopolysaccharides and proteinaceous material that become calcified with advancing age. These small tumors develop within the substance of the nerve tissue (bilateral in 70% of cases) and can lead to an elevated disc; they also may lead to a loss of visual field or, in rare cases, central acuity. They may be inherited as an autosomal trait with irregular penetrance. Disc drusen may be associated with retinitis pigmentosa and pseudoxanthoma elasticum.

Rarely, pseudopapilledema may be caused by remnants of the congenital hyaloid system and localized gliosis. An experienced observer can almost always distinguish these entities. Primary and metastatic optic nerve tumors can result in a swollen disc but ordinarily only when intraorbital disease is present and is seldom unaccompanied by other signs and symptoms of orbital disease, such as proptosis and motility disturbance. A host of inflammatory, infiltrative, and infectious conditions can cause true disc edema, which may be confused with true papilledema due to elevated intracranial pressure. In these cases, the swelling is usually unilateral (with the major exception of hypertensive crisis). Examples of infectious causes include syphilis, Lyme disease, and cat-scratch disease. Examples of inflammatory disorders that cause true disc edema include anterior ischemic optic neuropathy, optic neuritis, diabetes, sarcoidosis, and leukemic infiltration. These conditions should be seen as causes of papillitis, which is a distinct entity apart from pseudopapilledema.

Epidemiology
Frequency United States This condition affects 2-5% of the population. It is clinically apparent in only about 0.35% of individuals. Mortality/Morbidity Optic disc drusen may be associated with progressive visual field loss, more rarely loss of central acuity, and, in very rare cases, blindness. However, congenital causes are not associated with any progressive visual loss. Race Disc drusen are more common in whites and are believed to be less common in African Americans. Sex No sexual predilection exists. Age The condition occurs at any age, although disc drusen tend to enlarge with time and become more prominent with advancing age.

History

Most patients are asymptomatic. No visual symptoms are usually present. Visual field loss In many patients with disc drusen, visual field defects eventually develop along with afferent pupil defect, though patients usually remain symptom free. Transient visual obscurations A minority of patients with disc drusen experience transient visual flickering or graying out that is similar to transient visual obscurations that are sometimes seen in patients with papilledema. Rarely, patients might experience permanent visual loss from secondary processes. For example, disc drusen may increase the risk of later developing subretinal neovascular membranes, retinal vascular occlusion, or ischemic optic neuropathy. Visual acuity Patients with disc drusen may eventually lose central acuity. Although unusual, this visual loss would most likely follow a long period of gradual field constriction, otherwise this should arouse suspicion of another process.

Physical
Take a history concentrating on neurologic problems and symptoms, hypertension, and febrile illness. Perform visual acuity, color vision, and pupillary examinations. If present, document a relative afferent pupillary defect. Although the presence or absence of an afferent pupillary defect is not helpful diagnostically per se, generally, an afferent pupil defect is mild with early field loss. Blood pressure should be checked since optic nerve swelling can be a sign of malignant hypertension, a treatable systemic medical emergency. Perform a careful dilated fundus examination. Edema of the nerve fiber layer that blurs the disc margins and the peripapillary vasculature is a hallmark of true papilledema. Usually, the peripapillary vessels are clearly seen in pseudopapilledema, except in such cases as myelinated nerve fibers. The angle of the optic nerve head should be noted. A tilted disc results from an optic nerve that enters the eye at a sharply oblique angle; it usually has a characteristic appearance of a prominently elevated nasal aspect with a poorly defined or sunken temporal aspect. Patients with tilted discs may

have associated marked astigmatism or high myopia. Other anatomical variants include persistent hyaloid remnants, gliosis of the optic nerve head, and myelination of the nerve fiber layer. These entities have a characteristic appearance on dilated fundus examination. When superficial drusen (small, white-to-yellow, granular bulging of the substance of the disc) are present, they greatly aid in the diagnosis. At other times, drusen can be deeply buried in the substance of the nerve, and the clinical diagnosis is more subtle. Buried drusen may be visualized via retroillumination of the peripapillary retina and the sclera. See the image below.
Superficial optic nerve drusen. Note the irregular disc margins with preserved vascular and perivascular detail.

In papilledema, the disc is usually hyperemic with sometimes subtle dilatation of the superficial optic nerve vessels, and an increased frequency of hemorrhages and cotton-wool spots exists. Also, Paton lines and optociliary shunt vessels may be seen with retention of the central cup until late in the course of the disease. A severely crowded nerve due to other causes (eg, hyperopia, disc drusen) may display subtle congestion of optic nerve vasculature as well. In pseudopapilledema, the disc is yellow, the cup may be small or absent, venous congestion is not present, spontaneous venous pulsations are often present, congenitally anomalous vessels may be seen, and the disc abnormality may be familial. It may be fruitful to examine family members for disc drusen.

Causes
Congenitally anomalous disc Hyperopia Optic disc drusen Tilted disc Myelinated nerve fiber layer

Proceed to Differential Diagnoses

Differential Diagnoses
Idiopathic Intracranial Hypertension Optic Neuritis, Adult Optic Neuritis, Childhood Optic Neuropathy, Anterior Ischemic

Optic Neuropathy, Compressive Papilledema Sarcoidosis Scleritis Toxic/Nutritional Optic Neuropathy Toxoplasmosis Uveitis, Classification

Laboratory Studies

Laboratory studies are not usually necessary in the workup of patients with disc drusen. In patients with suspected Leber hereditary optic neuropathy, mitochondrial mutations are helpful. B-scan ultrasonography may be useful in identifying buried disc drusen. Because drusen are calcified, they demonstrate high reflectivity on ultrasound. While rarely indicated, a CT scan may show small areas of calcification within the disc substance, which represent calcified disc drusen. Progressive field loss, dyschromatopsia, or visual acuity loss in patients with suspected buried disc drusen or visible disc drusen warrants consideration of neuro-imaging studies to rule out occult CNS lesions, in which case a CT scan carries the advantage of possibly detecting buried disc drusen. Fluorescein angiography can be used to rule out true papilledema, which exhibits increased dilation of the peripapillary capillaries with late dye leakage. Disc drusen may autofluoresce on fluorescein angiography, which can be seen with red-free photo techniques, using the appropriate filters. (Buried disc drusen may not autofluoresce.) In Leber hereditary optic neuropathy, disc leakage is not seen on fluorescein angiography.

Imaging Studies

Other Tests
Visual field tests should be considered, especially if optic nerve drusen are suspected. Constriction of the visual field can gradually occur; patients rarely have progressive field loss that is insidious or rapid. Stereo color photographs of the optic discs are useful to document changes.

Procedures
No additional procedures are indicated. Proceed to Treatmen

Medical Care

No treatment is needed for most causes of pseudopapilledema because they represent normal physiologic variants. Diseases possibly associated with disc drusen may need treatment, such as subretinal neovascular membrane, central retinal vein occlusion, or ischemic optic neuropathy (largely to exclude giant cell arteritis in the appropriate age groups). A minority of patients with disc drusen (16-22%) present with progressive visual loss. Field deterioration normally occurs over many years and is generally slow and unnoticed by patients. Dramatic field loss related to vascular complications, such as anterior ischemic optic neuropathy, can rarely occur. Unfortunately, no successful therapy is available at this time. For patients who may suffer from glaucoma, it can be challenging to differentiate progressive glaucomatous field loss from field loss due to glaucoma. Estimation of the cup-to-disc ratio is also more challenging.
[1]

Surgical Care
No effective surgical treatment is available.

Complications Prognosis

With disc drusen, gradual loss of the peripheral visual field may occur and, rarely, loss of central vision. The visual prognosis is generally good.

Adult Optic Neuritis

Background
Optic neuritis (ON) is a demyelinating inflammation of the optic nerve that typically first occurs in young adulthood (see the image below). Many cases of ON are associated with multiple sclerosis (MS) or neuromyelitis optica (NMO), but ON can occur in isolation.[1] In cases associated with MS, ON is commonly the first manifestation of the chronic demyelinating process. [2] Long-term follow-up studies have indicated that up to 75% of female patients initially presenting with ON ultimately develop MS. (See Presentation and Prognosis.)
A case of acute optic neuritis. A. 1.5 Tesla, contrast-enhanced spin echo T1-weighted, fatsuppressed coronal MRI through the orbits shows enlargement and contrast enhancement of the left optic nerve in the retrobulbar portion (arrow). B. Coronal spin echo T1weighted, fat-suppressed MRI of the same patient shows enlargement and contrast enhancement of the nerve in a parasagittal oblique section (arrow).

Occasionally, ON can result from an infectious process involving the orbits

or paranasal sinuses or occur in the course of a systemic viral infection. [3, 4, 5, 6, 7, 8, 9, 10, 11] Certain optic neuropathies, such as anterior ischemic optic neuropathy (AION) and compressive and hereditary optic neuropathies, can resemble ON.[12] This article reviews ON as a primary demyelinating inflammation of the nerve occurring either in isolation or in association with MS or NMO. (NMO is a severe form of a demyelinating disease; it affects the optic nerves and the spinal cord, causing recurrent attacks of blindness and paralysis. [13, 14] ) Much information has been gleaned from the Optic Neuritis Treatment Trial (ONTT), and the reader is encouraged to review the follow-up data from this study. (See Etiology, Treatment, and Medication.)[15, 16, 17, 18] Patient education For patient education information, see Multiple Sclerosis.

Etiology
Most cases of ON are associated with MS, even though ON can occur in isolation. In MS-associated and isolated, monosymptomatic ON, the cause is presumed to be an autoimmune reaction that results in a demyelinating inflammation of the nerve. Pathologic studies in patients with ON associated with MS have shown that the demyelinative lesions in the optic nerve are similar to the MS plaques seen in the brain, with an inflammatory response marked by perivascular cuffing, T cells, and plasma cells. However, little is known about the pathology of isolated ON. In a single case of chronic, isolated ON, a biopsy specimen showed the presence of perivascular lymphocytic infiltration, multifocal demyelination, and reactive astrocytosis in the retrobulbar portion of the optic nerve. Abnormal intrathecal immunoglobulin G (IgG) synthesis, reflected as the presence of oligoclonal bands in the cerebrospinal fluid (CSF), is found in 60-70% of patients with isolated ON, suggesting an immunologic etiology similar to MS. NMO has been recognized as a distinct inflammatory demyelinating disease consisting of ON in combination with longitudinally extensive transverse myelitis. NMO is associated with the presence of a specific serum, NMO IgG autoantibody, which targets the water channel aquaporin-4.[19, 20, 21] As previously stated, ON can occasionally result from an infectious process involving the orbits or paranasal sinuses or occur in the course of a systemic viral infection.[3, 4, 5, 6, 7, 8, 9, 10, 11]

Epidemiology

Studies from Sweden and Denmark have reported an annual incidence of 45 cases of new-onset ON per 100,000 persons.[22] Patients living in temperate climates seem to be predisposed to ON. Race-, sex-, and age-related demographics ON appears to affect Caucasians more commonly than it does other races. Women are affected twice as often as men.[15] Typically, patients with first-time, acute ON are young adults aged 20-45 years. Atypical cases of ON may be seen in elderly patients. Bilateral ON in childhood is not uncommon, and it is believed there is less risk of progression to MS.

Prognosis
In contrast to ischemic optic neuropathies and compressive optic neuropathies, a gradual recovery of visual acuity with time is characteristic of ON.[23] For most patients with ON, visual function begins to improve 1 week to several weeks after onset, even without any treatment. However, permanent residual deficits in color vision and contrast and brightness sensitivity are common.[18] Decreased visual acuity secondary to ON may be permanent. Final visual outcome may be better in patients with an isolated episode of ON, compared with patients who eventually develop MS. Up to 75% of female patients and 35% of male patients initially presenting with ON ultimately develop MS.[24, 25, 26] Patients with silent demyelinative lesions elsewhere in the brain, observed on magnetic resonance imaging (MRI) performed at the initial presentation, are more likely to develop definite MS in the long term than are patients with isolated ON. In addition, patients who have recurrent episodes of ON may be more likely to develop MS. In patients with normal findings on MRI, a 16% risk of progression to clinically definite MS exists at 5-year follow-up. Most patients with relapsing NMO have an aggressive form of the disease that is associated with frequent and severe exacerbations and poor prognosis. Proceed to Clinical Presentation

History

A history of preceding viral illness may be present. Typically, patients with first time acute optic neuritis (ON) are otherwise healthy young adults. Patients with ON experience rapidly developing impairment of vision in 1

eye or, less commonly, both eyes during an acute attack.[27] Dyschromatopsia (change in color perception) in the affected eye occasionally may be more prominent than the decreased vision. [28] In nearly all cases, the visual changes are associated with a retro-orbital or ocular pain, usually exacerbated by eye movement. The pain may precede the visual loss. Patients may complain of vision loss exacerbated by heat or exercise (Uhthoff phenomenon). Objects moving in a straight line may appear to have a curved trajectory (Pulfrich phenomenon), presumably due to asymmetrical conduction between the optic nerves. Patients with MS may have recurrent attacks of ON. [29] Therefore, a history of previous episodes of decreased vision in the same or the fellow eye may be elicited. A previous history of neurologic problems, such as transient episodes of extremity/facial numbness or weakness, suggests a diagnosis of MS. A family history of MS may exist. NMO is characterized by ON and myelitis in a close temporal relationship. [30, 31, 32, 33] However, ON can occasionally precede the myelopathy. Some patients with NMO develop relapses limited to the optic nerves and spinal cord. In patients, especially males with bilateral, sequential optic neuropathy with little recovery of vision, exclude Leber hereditary optic neuropathy (LHON). Patients with LHON may have a history of vision loss in maternal uncles.

Physical Examination
In a typical first-time, acute case of ON, the general physical examination is normal. Pupillary light reaction is decreased in the affected eye and a relative afferent pupillary defect (RAPD) or Marcus Gunn pupil commonly is found. In bilateral cases, the RAPD may not be apparent. Measurement of visual acuity reveals varying degrees of reduction in vision, from a mildly decreased visual acuity to complete visual loss. However, visual acuity may be normal, with only a limited, mild visual-field defect. Almost all patients with decreased visual acuity also have abnormal contrast sensitivity and color vision, as revealed by examination using a Pelli-Robson chart and Ishihara color plates, respectively. Classic dictum states that a central scotoma most commonly is seen in ON. However, the Optic Neuritis Treatment Trial (ONTT) suggested that altitudinal field defects, arcuate defects, and nasal steps were more common than central scotomas and cecocentral scotomas. Visual field

examination typically shows a central scotoma. Peripheral extension of the scotoma in any direction, and even a generalized depression of the entire visual field, may be encountered. In acute ON, the fundus appears normal because two thirds of cases of ON are retrobulbar. With time, the optic nerve may become pale. One third of patients with ON have a swollen disc (papillitis). The disc edema of ON often is diffuse. The presence of segmental changes, altitudinal swelling, pallor, arterial attenuation, and splinter hemorrhages suggest other diagnoses (eg, AION).[34] If a dilated fundus examination is not performed, retinal problems, such as central serous retinopathy and retinal detachment, may be mistaken for ON.[35] Patients with NMO often develop a severe, bilateral form of ON and myelitis. Bitemporal or junctional visual-field defects, indicating chiasm involvement, may be present. Myelitis may be associated with localized back or radicular pain and Lhermitte's sign (spine or limbs paresthesias elicited by neck flexion) early in the course of the disease. Severe degrees of neurologic deficits, including paraplegia, are usual. Symptoms such as respiratory failure or hiccups may occur when the cervical spinal cord lesions extend into the medulla. Proceed to Differential Diagnoses

Diagnostic Considerations

Conditions to consider in the differential diagnosis of optic neuritis (ON) include the following: Neuromyelitis optica Hereditary optic neuropathies Nutritional optic neuropathies Wegener granulomatosis Necrotizing herpetic retinopathy in persons who are immunocompromised Branch retinal artery occlusion Central retinal artery occlusion Herpes simplex

Differential Diagnoses
Glaucoma, Angle Closure, Acute Interstitial Keratitis Meningioma, Optic Nerve Sheath Optic Neuropathy, Anterior Ischemic Optic Neuropathy, Compressive Sarcoidosis

Sudden Visual Loss Thyroid Ophthalmopathy Toxic/Nutritional Optic Neuropath yApproach Considerations Blood tests that can be considered to exclude causes of optic neuropathy other than demyelinating optic neuritis (ON) include the following: Erythrocyte sedimentation rate Thyroid function tests Antinuclear antibodies Angiotensin-converting enzyme Rapid plasma reagin Mitochondrial deoxyribonucleic acid (DNA) mutation studies However, in a typical case of ON without any clinical signs or symptoms of a systemic disease, the yield from these tests is extremely low. CSF analysis often is noncontributory to diagnosis. However, the presence of myelin basic protein, oligoclonal bands, and an elevated IgG index and synthesis rate in the CSF supports the diagnosis of MS. Even in the absence of other signs of MS during the initial presentation, patients with positive findings of demyelination in the CSF are more likely to develop MS in the long term.[36] Neuromyelitis optica (NMO)-IgG is a specific autoantibody marker for NMO.[13, 14]

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is highly sensitive and specific in assessing inflammatory changes in the optic nerves (see the image below) and helps to rule out structural lesions. In addition, MRI may have a value in predicting future development of MS in patients presenting with first-time, acute ON.[37, 38, 39, 40, 41, 42, 43]
A case of acute optic neuritis. A. 1.5 Tesla, contrast-enhanced spin echo T1-weighted, fatsuppressed coronal MRI through the orbits shows enlargement and contrast enhancement of the left optic nerve in the retrobulbar portion (arrow). B. Coronal spin echo T1weighted, fat-suppressed MRI of the same patient shows enlargement and contrast enhancement of the nerve in a parasagittal oblique section (arrow).

MRI performed at the initial presentation reveals that 10-20% of these patients may have clinically silent demyelinative lesions elsewhere in the brain. MRI at 3.0T is more sensitive to hyperintense lesions than is MRI at 1.5T.[44] These patients are more likely to develop definite MS in the long term than are patients with isolated ON. The Optic Neuritis Treatment Trial (ONTT) reported the 10-year risk of MS to be 56% with at least 1 MR T2 lesion.[15]

Utilization of fat saturation techniques helps to visualize gadolinium enhancement of the optic nerve and is the best imaging technique to visualize inflammation of the optic nerve. In addition to MRI of the optic nerves and brain/brainstem, MRI of the spinal cord is indicated in patients with suspected NMO. An MRI of the spinal cord characteristically shows cord swelling, signal changes, and enhancement extending over several levels consistent with longitudinally extensive myelitis.[45]

Visual Evoked Potentials

Visual evoked potentials (VEPs) are an important means of evaluating patients with suspected ON. They may be abnormal even when MRI of the optic nerve is normal. VEP often shows a loss of P100 response in the acute phase. P100 recovers with time, but it usually shows a markedly prolonged latency that persists indefinitely even after clinical recovery. VEP may be abnormal in patients without a past history of ON, thereby providing evidence of subclinical involvement of the optic nerve. For this reason, VEP often is performed in patients with a suspected diagnosis of MS. Proceed to Treatment & Management Proceed to Workup

Approach Considerations
Finding professional help early in the course of optic neuritis (ON) is important. The Optic Neuritis Treatment Trial (ONTT) was a carefully performed, randomized, clinical trial that yielded useful information. Despite the ONTT, the treatment of ON remains somewhat controversial.[46, 16] From a vision standpoint, observation without steroid treatment versus intravenous (IV) steroid treatment showed no difference in ultimate visual outcome at the 5-year mark.[47] In a case series of 20 patients with highly relapsing NMO, Kim et al reported significantly reduced relapse rates and clinical stabilization or improvement with mitoxantrone treatment.[48] Further studies conducted in a prospective and controlled fashion are required to determine whether mitoxantrone is a viable treatment option. Early reports with a small number of patients found some benefit with plasma exchange in acute, severe ON. Further controlled studies are recommended.

Inpatient care Patients with NMO often require supportive care, as they are prone to many complications, such as deep venous thrombosis, pulmonary embolism, urinary tract infection, decubiti, and contractures related to the myelopathy. Mechanical ventilation may be needed due to respiratory compromise. Consultations Consultations with ophthalmology and neurology are recommended for complete evaluation and treatment of suspected ON cases.

Steroid Therapy
The ONTT showed strong evidence against the use of oral steroids in isolation in the treatment of ON, because oral steroids alone caused an increased rate of recurrence of ON.[17] IV steroids (methylprednisolone 250 mg qid for 3 days with oral steroid taper) decreased the short-term risk of development of MS in patients with central nervous system (CNS) white matter plaques, but they had no longterm protective benefit from MS. IV steroids do little to affect the ultimate visual acuity in patients with ON, but they do speed the rate of recovery. Some clinicians advocate IV steroids in patients with severe visual loss or bilateral visual loss. IV steroids are sometimes administered in an outpatient setting or at home. Admission to the hospital is recommended for the duration of high-dose intravenous steroid treatment because of the potential risk of serious adverse effects from this treatment. Patients with NMO often respond to IV methylprednisolone. Plasma exchange has been used in patients with no significant improvement with steroids.[49, 50] Proceed to Medication Pharmacologic therapy in optic neuritis (ON) is directed at ameliorating the acute symptoms of pain and decreased vision caused by demyelinating inflammation of the nerve. Varying regimens of corticosteroids have been used for this purpose. A 3-day course of high-dose IV methylprednisolone followed by a rapid oral taper of prednisone has been shown to provide a rapid recovery of symptoms in the acute phase. (In addition, this treatment may delay the short-term development of MS after ON.) However, IV steroids do little to affect the ultimate visual acuity in patients with ON.

Medication Summary

For patients with ON whose brain lesions on MRI indicate a high risk of developing clinically definite MS, treatment with immunomodulators (eg, interferon beta-1a, interferon beta-1b, glatiramer acetate) may be considered.[51] IV immunoglobulin (IVIG) treatment of acute ON has been shown to have no beneficial effect.

Corticosteroids
Class Summary These have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.
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Methylprednisolone (Solu-Medrol, Depo-Medrol, Medrol) Methylprednisolone is a synthetic corticosteroid used intravenously as an anti-inflammatory and immunosuppressant agent. It has been shown to facilitate the recovery of vision in the acute phase of ON even though it may not change the long-term visual outcome. In addition, treatment with methylprednisolone may delay the development of MS.
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Prednisone Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. It is a commonly used oral agent. Prednisone is used for an oral taper of steroids, which may reduce the emotional effects of steroid withdrawal and the risk of the development of adrenocortical insufficiency. However, these risks are not very high after only 3 days of treatment with high-dose steroids, and most neurologists do not use a prednisone taper.
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Prednisolone (Pediapred, Prelone, Orapred) Prednisolone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. It is a commonly used oral agent. Prednisolone is used for an oral taper of steroids, which may reduce the emotional effects of steroid withdrawal and the risk of the development of adrenocortical insufficiency. However, these risks are not very high after only 3 days of treatment with high-dose steroids, and most neurologists do not use a prednisone taper.

NEURITIS OPTIK
PENDAHULUAN
Nervus opticus adalah saraf yang membawa informasi visual dari retina ke otak. Nervus opticus terdiri dari sekitar 1 juta akson yang berasal dari ganglion sel retina. Serat sarafnya menjadi bermielin saat meninggalkan mata. Nervus opticus bergabung membentuk chiasma opticum.1

ETIOLOGI
Neuritis optik adalah peradangan dari nervus opticus, yang dapat disebabkan oleh: 1. Demielinisasi Idiopatik Sklerosis multipel Neuromyelitis optica (Devics disease) 2. Immune mediated Neuritis optik setelah infeksi virus1,2 Neuritis optik setelah imunisasi Acute disseminated encephalomyelitis Guillain Barre syndrome Lupus eritematosus sistemik 3. Infeksi langsung Herpes zoster, syphilis, tuberculosis, cryptococcosis, cytomegalovirus 4. Granulomatous optic neuropathy Sarcoidosis Idiopatik 5. Contiguous inflammatory disease Peradangan dalam bola mata Peradangan intracranial: meningitis, encephalitis1 Pada referat ini yang akan dibahas adalah yang disebabkan oleh kelainan demyelinative, yang merupakan penyebab tersering pada orang dewasa.

EPIDEMIOLOGI
Insidensi neuritis optik per tahun adalah 5 per 100.000 penduduk. Ras kaukasian lebih banyak terkena dibanding ras lain. Biasanya unilateral dan lebih banyak pada wanita (3:1), dengan predileksi umur dewasa muda 20-45 tahun. Pada anak lebih umum terkena bilateral dan timbul papilitis tapi dengan kecenderungan menjadi sklerosis multipel yang lebih rendah. 1 Kasus neuritis optik pada anak lebih jarang dibanding kasus pada orang dewasa, kurang lebih 5% kasus.3

PATOFISIOLOGI
Pada neuritis optik, baik yang dihubungkan dengan sklerosis multipel ataupun yang idiopatik, dipercaya faktor yang berperan adalah reaksi autoimun. Penelitian pada pasien neuritis optik dengan sklerosis multipel menunjukkan bahwa lesi demielinisasi pada nervus optikus serupa dengan lesi sklerosis multipel pada otak, dengan tanda radang.4

KLASIFIKASI
Ada 2 bentuk dari neuritis optik, yang pertama papilitis yang merupakan peradangan papil saraf optik dalam bola mata, dan neuritis retrobulbar yang merupakan radang saraf optik yang terletak di belakang bola mata.2

DIAGNOSA
Anamnesa Riwayat Pasien dengan sklerosis multipel dapat mempunyai riwayat neuritis optik yang berulang, dapat ditanyakan apakah pernah terjadi sebelumnya keluhan yang sama. Pada anamnesa akan didapatkan gejala subjektif: 1. Penglihatan turun mendadak dalam beberapa jam sampai hari yang mengenai satu atau kedua mata. Kurang lebih sepertiga pasien memiliki visus lebih baik dari 20/40 pada serangan pertama, sepertiga lagi juga dapat memiliki visus lebih buruk dari 20/200. 2. Penglihatan warna terganggu. 3. Rasa sakit bila mata bergerak dan ditekan, dapat terjadi sebelum atau bersamaan dengan berkurangnya tajam penglihatan. Bola mata terasa berat di bagian belakang bila digerakkan. 4. Adanya defek lapang pandang. 5. Pasien mengeluh penglihatan menurun setelah olahraga atau suhu tubuh naik (tanda Uhthoff).1,2,4 6. Beberapa pasien mengeluh objek yang bergerak lurus terlihat mempunyai lintasan melengkung (Pulfrich phenomenon), kemungkinan dikarenakan konduksi yang asimetris antara nervus optikus.4 Pemeriksaan Dilakukan pemeriksaan untuk melihat gejala objektif. Langkah-langkah pemeriksaan: 1. Pemeriksaan visus Didapatkan penurunan visus yang bervariasi mulai dari ringan sampai kehilangan total penglihatan. 2. Pemeriksaan segmen anterior Pada pemeriksaan segmen anterior, palpebra, konjungtiva, maupun kornea dalam keadaan wajar. Refleks pupil menurun pada mata yang terkena dan defek pupil aferen relatif atau Marcus Gunn pupil umumnya ditemukan. Pada kasus yang bilateral, defek ini bisa tidak ditemukan.1,2,4,5 3. Pemeriksaan segmen posterior Pada neuritis optik akut sebanyak dua pertiga dari kasus merupakan bentuk retrobulbar, maka papil tampak normal, dengan berjalannya waktu, nervus optikus dapat menjadi pucat akibat atrofi. Pada kasus neuritis optik bentuk papilitis akan tampak edema diskus yang hiperemis dan difus, dengan perubahan pada pembuluh darah retina, arteri menciut dan vena melebar. Jika ditemukan gambaran eksudat star figure, mengarahkan diagnosa kepada neuroretinitis.1,2,5 Pemeriksaan Tambahan - Tes konfrontasi - Tes ishihara untuk melihat adanya penglihatan warna yang terganggu 2,4,5, umumnya warna merah yang terganggu.5

Pemeriksaan Anjuran

Untuk membantu mencari penyebab neuritis optik biasanya dilakukan pemeriksaan foto sinar X kanal optik, sela tursika, atau dilakukan pemeriksaan CT orbita dan kepala. Dengan MRI dapat dilihat tanda-tanda sklerosis multipel.1,4,5

DIAGNOSIS BANDING
Diagnosis banding dari neuritis optik adalah: - Iskemik optik neuropati Tidak sakit dengan skotoma altitudinal - Edema papil Merupakan edema dari papil akibat peningkatan tekanan intrakranial, biasanya terjadi bilateral, tajam penglihatan yang normal terkoreksi, refleks pupil yang normal, dan lapang pandang yang intak kecuali pembesaran bintik buta. - Ablasi retina - Oklusi arteri retina sentral - Obstruksi vena retina sentral - Toksik neuropati1,2,4

TERAPI
Terapi steroid digunakan karena mungkin dapat mempersingkat periode akut penyakit 1,2,4, namun tidak mempengaruhi hasil akhir dari penglihatan.1,4 Pada penelitian Optic Neuritis Treatment Trial di Amerika Serikat, prednisolone oral sendiri tidak meningkatkan kecepatan kembalinya tajam penglihatan dan meningkatkan resiko terjadinya neuritis optik rekuren.1,4

KOMPLIKASI
Kehilangan penglihatan pada neuritis optik dapat permanen.

PROGNOSA
Penyembuhan pada neuritis optik berjalan secara bertahap. Pada banyak pasien neuritis optik, fungsi visual mulai membaik 1 minggu sampai 3 minggu setelah onset penyakit walau tanpa pengobatan.1,2,4 Namun sisa defisit dalam penglihatan warna, kontras, serta sensitivitas adalah hal yang umum.4 Penglihatan akhir pada pasien yang mengalami neuritis optik dengan sklerosis multipel lebih buruk dibanding dengan pasien neuritis optik idiopatik.4 Biasanya visus yang buruk pada episode akut penyakit berhubungan dengan hasil akhir visus yang lebih buruk juga, namun kadang kehilangan persepsi cahaya pun dapat diikuti dengan kembalinya visus ke 20/20. Hasil akhir visus yang buruk juga dihubungkan dengan panjangnya lesi yang terkena, khususnya jika terlibatnya nervus dalam canalis optikus.1 Tiap kekambuhan akan menyebabkan pemulihan yang tidak sempurna dan memperburuk penglihatan.

BAB II TINJAUAN PUSTAKA

II.1 ANATOMI DAN FISIOLOGI II.1.1 Lapisan Retina

Gambar 1. Lapisan retina

Komponen yang paling utama dari retina adalah sel-sel reseptor sensoris atau fotoreseptor dan beberapa jenis neuron dari jaras penglihatan. Lapisan terdalam (neuron pertama) retina mengandung fotoreseptor (sel batang dan sel kerucut) dan dua lapisan yang lebih superfisial mengandung neuron bipolar (lapisan neuron kedua) serta sel-sel ganglion (lapisan neuron ketiga). 1,2,3 Sel batang berfungsi dalam proses penglihatan redup dan gerakan sementara sel kerucut berperan dalam fungsi penglihatan terang, penglihatan warna, dan

ketajaman penglihatan. Sel batang memiliki sensitivitas cahaya yang lebih tinggi daripada sel kerucut dan berfungsi pada penglihatan perifer. Sel kerucut mampu membedakan warna dan memiliki fungsi penglihatan sentral. Badan sel dari reseptor-reseptor ini mengeluarkan tonjolan (prosesus) yang bersinaps dengan sel-sel ganglion retina. Akson sel-sel ganglion membentuk lapisan serat saraf pada retina dan menyatu membentuk saraf optikus. 1,3

II.1.2 Nervus Optikus

Gambar 2. Jaras nervus optikus

Nervus optikus bermula dari optik disk dan berlanjut sampai ke kiasma optikum, dimana ke dua nervus tersebut menyatu. Lebih awal lagi merupakan kelanjutan dari lapisan neuron retina, yang terdiri dari axon-axon dari sel ganglion. Serat ini juga mengandung serat aferen untuk reflex pupil. Secara morfologi dan embriologi, neuritis optikus merupakan saraf sensorik. Tidak seperti saraf perifer nervus optikus tidak dilapisi oleh

neurilema sehingga tidak dapat beregenerasi jika terpotong. Serat nervus optikus mengandung 1,0-1,2 juta serat saraf. 4

Bagian nervus optikus Nervus optikus memiliki panjang sekitar 47-50 mm, dan dapat di bagi mejadi 4 bagian : Intraocular (1 mm) : menembus sklera (lamina kribrosa), koroid dan masuk ke mata sebagai papil disk. Intraorbital (30 mm) : memanjang dari belakang mata sampai ke foramen optik. Lebih ke posterior, dekat dengan foramen optik, dikelilingi oleh annulus zinn dan origo dari ke empat otot rektus. Sebagian serat otot rektus superior berhubungan dengan selubung saraf nervus optikus dan berhubungan dengan sensasi nyeri saat menggerakkan mata pada neuritis retrobulbar. Secara anterior, nervus ini dipidahkan dari otot mata oleh lemak orbital. Intrakanalikular (6-9 mm) : sangat dekat dengan arteri oftalmika yang berjalan inferolateral dan melintasi secara oblik, dan ketika memasuki mata dari sebelah medial. Ini juga menjelaskan kaitan sinusitis dengan neuritis retrobulbar. Intrakranial (10 mm) : melintas di atas sinus kavernosus kemudian menyatu membentuk kiasma optikum. 1, 4

Selubung meningeal Piamater, arachnoid, dan duramater melapisi otak dan berlanjut ke nervus optikus. Di kanalis optik dura mater menempel langsung ke tulang sekitarnya. Ruang subarachnoid dan ruang subdural merupakan kelanjutan dari bagian otak juga. 1, 4

Vaskularisasi nervus optikus Permukaan optic disk didarahi oleh kapiler-kapiler dari arteri retina. Daerah prelaminar terutama di suplai dari sentripetal cabang cabang dari peripailari koroid dan sebagian kontibusi dari pembuluh darah dari lamina cribrosa. 1, 4 Lamina kribrosa disuplai dari cabang arteri siliaris posterior dan arteri circle of zinn. Bagian retrolaminar nervus optikus di suplai dari sentrifugal cabang-cabang arteri retina sentral dan sentripetal cabang-cabang pleksus yang dibentuk dari arteri koroidal, circle of zinn, arteri retina sentral, dan arteri oftalmika. 1, 4

Gambar 3. Vaskularisasi Nervus Optikus

II.1.3.

Lesi Saraf Optik Ditandai dengan hilangnya penglihatan atau kebutaan lengkap pada sisi yang

terkena dengan hilang nya refleks cahaya langsung pada sisi ipsilateral dan reflek tidak langsung pada sisi kontralateral. 3, 4 Penyebab umum dari lesi saraf optik adalah: optik atrofi, trauma pada saraf optik, neuropati optik, dan neuritis optikus akut.

Gambar 4. Defek Visual

Lesi melalui bagian proksimal saraf optik Gambaran penting dari lesi tersebut yaitu hemianopsia ipsilateral dan kontralateral, hilangnya refleks cahaya langsung pada sisi yang terkena dan reflek cahaya tidak langsung pada sisi kontralateral. 1, 3, 4 Lesi kiasma sentral Dicirikan oleh hemianopsia bitemporal dan kelumpuhan refleks pupil. Biasanya diahului oleh atrofi optik pada sebagian akhir nervus optikus. Penyebab umum lesi kiasma pusat adalah suprasellar aneurisma, tumor kelenjar hipofise, kraniofaringioma, meningioma suprasellar, glioma ventrikel ketiga, hidrosefalus akibat obstruktif ventrikel tiga, dan kiasma arachnoiditis kronis. 1, 3, 4

Lesi kiasma lateral Gambaran menonjol pada lesi ini yaitu hemianopia binasal dengan kelumpuhan refleks pupil. Penyebab umum dari lesi tersebut diantaranya penggelembungan dari ventrikel ketiga yang menyebabkan tekanan pada setiap sisi kiasma dan ateroma dari carotis atau arteri communican posterior. 1, 3, 4 Lesi saluran optik Ditandai dengan hemianopia homonim terkait dengan reaksi pupil kontralateral (Reaksi Wernicke). Lesi ini biasanya diahului oleh atrofi optik pada sebagian akhir nervus optikus dan mungkin berhubungan dengan kelumpuhan saraf ketiga kontralateral serta hemiplegik ipsilateral. Penyebab umum lesi ini diantaranya lesi sifilis, tuberkulosis, dan aneurisma dari serebeli atas atau arteri serebral posterior. 1, 3, 4 Lesi badan genikulatam lateral Lesi ini mengakibatkan hemianopia homonim dengan refleks pupil minimal, dan mungkin berakhir dengan atrofi optik parsial. 1, 3, 4 Lesi radiasi optik Gambaran berbeda-beda tergantung pada lokasi lesi. Keterlibatan radiasi optik total mengakibatkan hemianopsia homonim total. Hemianopia kuadrantik inferior ( pie on the floor) terjadi pada lesi lobus parietal (mengandung serat unggul radiasi optik). Hemianopia kuadrantik superior (pie on the sky) dapat terjadi setelah lesi dari lobus temporal (mengandung serat radiasi optik inferior). Biasanya lesi dari radiasi optik terjadi akibat oklusi pembuluh darah, tumor primer dan sekunder, serta trauma. 1, 3, 4 Lesi korteks visual Kerusakan makula homonim pada lesi ujung korteks oksipital yang dapat terjadi sebagai akibat cedera kepala atau cedera ditembak senapan. Refleks cahaya pupil normal dan atrofi optik tidak diikuti lesi korteks visual. 1, 3, 4

Lesi jalur visual Kerusakan makula homonim pada lesi ujung korteks oksipital yang dapat terjadi sebagai akibat cedera kepala atau cedera ditembak senapan. Refleks cahaya pupil normal dan atrofi optik tidak diikuti lesi korteks visual. 1, 3, 4

II.2 Definisi dan Klasifikasi Neuritis optik adalah radang nervus optikus; penyakit ini dapat diklasifikasikan ke dalam bentuk : 6. intraokular, yang mengenai bagian saraf bola mata (papillitis) 7. retrobulbar, yang mengenai bagian saraf di belakang bola mata1,2,5

II.3 Epidemiologi Studi epidemiologi menunjukan kejadian neuritis optikus berkisar 4-5 per 100.000 populasi, dengan insidensi tertinggi pada populasi yang tinggal di dataran tinggi, seperti Amerika Utara dan Eropa bagian barat, dan terendah pada daerah ekuator. Sedangkan dari segi ras, ras kaukasian lebih banyak terkena dibanding ras lain. Pada predileksi umur dewasa muda 20-45 tahun, neuritis optikus biasanya bersifat unilateral dan lebih banyak pada wanita (3:1). Sedangkan neuritis optik pada anak lebih jarang terjadi, yaitu hanya kurang lebih 5% kasus, biasanya bersifat bilateral, timbul palpitis, dan mempunyai kecenderungan menjadi sklerosis multipel lebih rendah. 3,6

II.4 Etiologi Demielinatif1 a. Idiopatik b. Sklerosis multiple c. Neuromielitis optika (penyakit Delvic)

 Diperantarai imun1 7. Neuritis optik pascainfeksi virus (morbili, mumps, cacar air, influenza, mononukleosis infeksiosa) 8. Neuritis optik pascaimunisasi 9. Ensefalomielitis diseminata akut 10. Polineuropati idiopatik akut (sindrom Guillain-Barre)

11.Lupus eritematosus sistemik 12. Penyakit leber

Infeksi langsung1 - Herpes zoster, sifilis, tuberkulosis, crytococcosis, cytomegalovirus Neuropati optik granulomatosa1 - Sarkoidosis - Idiopatik Penyakit peradangan sekitar1 - Peradangan intraocular - Penyakit orbita - Penyakit sinus, termasuk mukormikosis - Penyakit intracranial: meningitis, ensefalitis Intoksikasi racun eksogen3 tobacco, etil alkohol, metil alkohol penyakit metabolic7 diabetes, anemia, kehamilan, avitaminosis

II.5 Patogenesis

Dasar patologi penyebab neuritis optikus paling sering adalah inflamasi demielinisasi dari saraf optik. Patologi yang terjadi sama dengan yang terjadi pada multipel sklerosis (MS) akut, yaitu adanya plak di otak dengan perivascular cuffing, edema pada selubung saraf yang bermielin, dan pemecahan mielin.7, 8 Inflamasi pada endotel pembuluh darah retina dapat mendahului demielinisasi dan terkadang terlihat sebagai retinal vein sheathing. Kehilangan mielin dapat melebihi hilangnya akson.7, 8 Dipercaya bahwa demielinisasi yang terjadi pada Neuritis optikus diperantarai oleh imun, tetapi mekanisme spesifik dan antigen targetnya belum diketahui. Aktivasi sistemik sel T diidentifikasi pada awal gejala dan mendahului perubahan yang terjadi didalam cairan serebrospinal. Perubahan sistemik kembali menjadi normal mendahului perubahan sentral (dalam 2-4 minggu). Aktivasi sel T menyebabkan pelepasan sitokin dan agen-agen inflamasi yang lain. Aktivasi sel B melawan protein dasar mielin tidak terlihat di darah perifer namun dapat terlihat di cairan serebrospinal pasien dengan Neuritis optikus. Neuritis optikus juga berkaitan dengan kerentanan genetik, sama seperti MS. Terdapat ekspresi tipe HLA tertentu diantara pasien neuritis optikus. 7, 8

II.6 Gejala dan Tanda Keluhan utama pada neutiris optikus adalah sama, baik pada papilitis, dimana saraf yang terkena terletak intraokular, maupun pada neuritis retrobulbar yang mengenai saraf ekstra okular. 3 Gambaran akut - Gejala neuritis optik biasanya monokular, namun dapat mengenai kedua mata terutama pada anak-anak. 2, 6 - Hilangnya penglihatan tiba-tiba selama beberapa jam sampai beberapa hari 2, 6 - Nyeri pada mata

Nyeri ringan di dalam atau sekitar mata terdapat pada lebih dari 90% pasien. Nyeri tersebut dapat terjadi sebelum atau bersama-sama dengan hilangnya penglihatan dan berlangsung selama beberapa hari. Rasa sakit akan bertambah bila bola mata ditekan dan disertai sakit kepala.
2

Pergerakan okular terutama gerakan ke atas dan ke bawah juga dapat memperberat nyeri ini karena perlekatan sejumlah serat otot rektus superior dengan duramater. 2, 6 - Defek pupil aferen (afferent pupillary defect)

Gambar 5. Defek pupil aferen

Selalu terjadi pada neuritis optik bila mata yang lain tidak ikut terlibat. Adanya defek pupil aferen ini ditunjukkan dengan pemeriksaan swinging light test (Marcus-Gunn pupil). MarcusGunn positif ialah apabila pada mata yang sehat diberi cahaya, maka terjadi miosis pada kedua mata. Namun bila cahaya dipindahkan pada mata yang sakit, maka kedua pupil akan melebar. 2, 6,
9

- Defek lapang pandang Pada neuritis optik, lapang penglihatan perifer menyempit secara konsentris, terdapat skotoma sentral dengan bermacam tebal dan besarnya. Dapat pula berbentuk sekosentral atau para sentral. 2, 6 - Buta warna pada mata yang terkena, terjadi pada 88% pasien. 2, 6, 9

Gambaran Kronik Walaupun telah terjadi penyembuhan secara klinis, tanda neuritis optik masih dapat tersisa. Tanda kronik dari neuritis optik yaitu:

- Kehilangan penglihatan secara persisten. Kebanyakan pasien neuritis optik mengalami perbaikan penglihatan dalam 1 tahun. 2, 6 - Defek pupil aferen relatif tetap bertahan pada 25% pasien dua tahun setelah gejala awal. 2, 6 - Desaturasi warna, terutama warna merah. Pasien dengan desaturasi warna merah akan melihat warna merah sebagai pink, atau orange bila melihat dengan mata yang terkena. 2, 6 - Fenomena Uhthoff yaitu terjadinya eksaserbasi temporer dari gangguan penglihatan yang timbul dengan peningkatan suhu tubuh. Olahraga dan mandi dengan air panas merupakan pencetus klasik. 2, 6 - Diskus optik terlihat mengecil dan pucat, terutama didaerah temporal. Pucatnya diskus meluas sampai batas diskus ke serat retina peripapil. 2, 6

II.7 Diagnosis Anamnesis 1, 7, 8 4. Penglihatan yang kabur (visus turun) mendadak 5. Adanya bintik buta 6. Perbedaan subjektif pada terangnya cahaya 7. Persepsi warna yang terganggu 8. Kekaburan penglihatan ketika beraktivitas dan meningkatnya suhu dan berkurang jika beristirahat. 9. Rasa sakit pada mata yang mengganggu dan lebih sering pada tipe neuritis retrobulbar daripada tipe papilitis. 10. Gejala berlangsung sementara pada salah satu mata (pada pasien dewasa). Sedangkan pada pasien anak, biasanya mengenai kedua mata. Terdapat riwayat demam atau imunisasi sebelumnya pada anak akan mendukung diagnosis.

Pemeriksaan Fisik 1, 7, 8 Pemeriksaan visus. Hilangnya visus dapat ringan (20/30), sedang (20/60), maupun berat (20/70). Pemeriksaan lapang pandang, biasanya berupa skotoma sentral atau sentrosekal. Namun setelah 7 bulan, 51 % kasus memiliki lapangan pandang yang normal. Refleks pupil. Defek aferen pupil terlihat dengan refleks cahaya langsung yang menurun atau hilang. Penglihatan warna berkurang. Adaptasi gelap mungkin menurun.

Pemeriksaan penunjang 1, 6, 7, 8 1. Funduskopi - Pemeriksaan funduskopi pada papilitis terlihat gambaran hiperemia dan edema diskus optik sehingga membuat batas diskus tidak jelas. Pada papil terlihat perdarahan, eksudat star figure yang menyebar dari papil ke makula, dengan perubahan pada pembuluh darah retina dan arteri menciut dengan vena yang melebar. Kadang-kadang terlihat edema papil yang besar yang menyebar ke retina. Edema papil tidak melebihi 2-3 dioptri.

Gambar 6. Edema nervus optikus pada neuritis optikus

- 60% pasien dengan neuritis retrobulbar memiliki gambaran funduskopi yang normal. Hal ini menyebabkan adanya suatu istilah The patient sees nothing and the doctor sees nothing. Namun apabila prosesnya sangat destruktif, dapat berakhir sebagai optik atrofi dan papil menjadi pucat, tak berbatas tegas, dan matanya buta. - Perdarahan peripapil, jarang pada neuritis optik tetapi sering menyertai papilitis karena neuropati optik iskemik anterior. - Tanda lain adanya inflamasi pada mata yang terdeteksi pada pemeriksaan funduskopi yaitu: perivenous sheathing. 2. MRI (magnetic resonance imaging) MRI diperlukan untuk melihat nervus optikus dan korteks serebri. Hal ini dilakukan terutama pada kasus-kasus yang diduga terdapat sklerosis multipel. 3. Pungsi lumbal dan pemeriksaan darah Dilakukan untuk melihat adanya proses infeksi atau inflamasi. 4. Slit lamp Adanya sel radang pada vitreous 5. Visually evoked response (VER) terganggu dan menunjukan penurunan amplitude dan perlambatan waktu transmisi.

II.8 Diagnosis Banding2,3 Neuritis Optik Papiledema Iskemik Gejala Visus Visus sentral hilang Visus tidak hilang; cepat, progresif, jarang ketajaman dipelihara kegelapan yang transien Defek akut lapang pandang; ketajaman bervariasi turun Neuropati Optik

akut

Lain

Bola mata pegal; sakit bila digerakkan; sakit

Sakit kepala, mual, muntah, tanda fokal neurologis lain Tidak ada

Biasanya nihil;

Sakit bergerak

alis atau orbita Ada

Tidak ada

Bilateral

Jarang pada orang dewasa; sering

Selalu bilateral

Khas unilateral pada stadium akut

Gejala

pada anak-anak Tidak ada isokoria;

Tidak ada isokoria;

Tidak ada isokoria;

Pupil

Reaksi sinar menurun pada sisi

Reaksi normal

Reaksi sinar menurun pada sisi infark disk

Penglihatan warna

neuritis Turun

Normal

Ketajaman visus

Biasanya menurun

Normal

Bervariasi

Lapang pandang

Skotoma sentral

Membesar; ada blind spot

Skotoma sentral

Sel badan kaca

Ada

Tidak ada

Tidak ada

Funduskopi

Retrobulbar : nomal.

Papilitis : - Media Keruh pada posterior vitreous - Warna diskus - Pinggir diskus - Edema diskus Hiperemia Kabur Biasanya tidak melebihi 3 diopter - Edema peripapillary - Perdarahan retina - Retinal exudate - Makula Prognosis visus Macular fan bisa ada Visus biasanya kembali normal atau tingkat fungsional Fluorescein angiography Kebocoran zat kontras sedikit Macular star bisa ada Baik dengan menghilangkan kausa tekanan intra-kranial Vertical oval pool zat kontras akibat kebocoran Tidak ada Prognosis buruk untuk kembali, mata kedua lamalama terlibat dalam 1/3 kasus idiopatik Ada kebocoran zat kontras di peripapillary Kurang jelas Sangat jelas Jelas Biasanya tidak ada Jelas Jelas Ada Ada Ada Merah Kabur 2 6 diopter Pucat Kabur Bengkak Bening Bening

II.9

Penatalaksanaan Pasien tanpa riwayat Multiple Sclerosis atau Neuritis optikus :

- Dari hasil MRI bila terdapat minimum 1 lesi demielinasi tipikal : Regimen selama 2 minggu : o 3 hari pertama diberikan Methylprednisolone 1kg/kg/hari i.v o 11 hari setelahnya dilanjutkan dengan Prednisolone 1mg/kg/hari oral o Tapering off dengan cara 20 mg prednisone oral untuk hari pertama (hari ke 15 sejak pemberian obat) dan 10 mg prednisone oral pada hari ke-2 sampai ke-4 o Dapat diberikan Ranitidine 150 mg oral untuk profilaksis gastritis6,10,11 Menurut Neuritis optikus Treatment Trial (ONTT) pengobatan dengan steroid dapat menurunkan progresivitas Multiple sclerosis selama 3 tahun. Terapi steroid hanya mempercepatkan pemulihan visual tapi tidak meningkatkan hasil pemulihan pandangan visual. 11 - Dari hasil MRI bila 2 atau lebih lesi demielinasi : o Menggunakan regimen yang sama dengan yang di atas. o Merujukan pasien ke spesialis neurologi untuk terapi interferon -1 intramuskular seminggu sekali selama 28 hari. o Metilprednisolon IV (1 g per hari, dosis tunggal atau dosis terbagi selama 3 hari) diikuti dengan prednison oral (1 mg/kg BB/hari selama 11 hari kemudian 4 hari tappering off ). Tidak menggunakan oral prednisolone sebagai terapi primer karena dapat meningkatkan resiko rekuren atau kekambuhan. 6,10,11 - Dengan tidak ada lesi demielinasi dari hasil MRI : a. Risiko terjadi MS rendah, kemungkinan terjadi sekitar 22% setelah 10 tahun kemudian b. Intravena steroid dapat digunakan untuk mempercepatkan pemulihan visual c. Biasanya tidak dianjurkan untuk terapi kecuali muncul gangguan visual pada mata kontralateral

d. MRI lagi dalam 1 tahun kemudian6,10,11

Mitoxantrone, suatu agen kemoterapi dan terapi antibiotik di monoklonal telah memberikan hasil yang menjanjikan bagi penyakit kambuhan-remisi (relapsing-remitting disease) yang progresif dan sulit diatasi. 10

II.10 Komplikasi Kehilangan penglihatan pada neuritis optik dapat terjadi permanen. Neuritis retrobulbar mungkin terjadi walaupun merupakan suatu neuritis optik yang terjadi cukup jauh di belakang diskus optikus.6, 7 Neurits optik yang disebabkan oleh sklerosis multipel memiliki ciri khas kekambuhan dan remisi. Disabilitas yang menetap cenderung meningkat pada setiap kekambuhan. Peningkatan suhu tubuh dapat memperparah disabilitas (fenomena Uhthoff) khususnya gangguan penglihatan. 6, 7

II.11 Prognosis Penyembuhan pada neuritis optik berjalan secara bertahap. Pada banyak pasien neuritis optik, fungsi visual mulai membaik 1 minggu sampai 3 minggu setelah onset penyakit walau tanpa pengobatan. Namun sisa defisit dalam penglihatan warna, kontras, serta sensitivitas adalah hal yang umum. Kelainan tajam penglihatan (15-30%), sensitivitas kontras (63-100%), penglihatan warna (33-100%), lapang pandang (62-100%), stereopsis (89%), terang gelap (89 100%), reaksi pupil aferen (5592%), diskus optikus (6080%), dan visual-evoked potential (63100%). Rekurensi dapat terjadi pada mata yang lain, kira-kira 30% dalam 5 tahun. 1, 6 Penglihatan akhir pada pasien yang mengalami neuritis optik dengan sklerosis multiple lebih buruk dibanding dengan pasien neuritis optik idiopatik.3,7

Biasanya visus yang buruk pada episode akut penyakit berhubungan dengan hasil akhir visus yang lebih buruk juga, namun kadang kehilangan persepsi cahaya pun dapat diikuti dengan kembalinya visus ke 20/20. Hasil akhir visus yang buruk juga dihubungkan dengan panjangnya lesi yang terkena, khususnya jika terlibatnya nervus dalam kanalis optikus.3,7 Tiap kekambuhan akan menyebabkan pemulihan yang tidak sempurna dan memperburuk penglihatan. 3,7

Proses penyembuhan dan pemulihan ketajaman penglihatan terjadi pada 92% pasien. Jarang yang mengalami kehilangan penglihatan yang progresif. Meskipun demikian, penglihatan tidak dapat sepenuhnya kembali normal.