Other Inflammatory Optic Neuropathies

Chapter 21

OTHER INFLAMMATORY OPTIC NEUROPATHIES

Larry P. Frohman

This chapter deals with other forms of inflammatory optic neuropathy aside from the idiopathic optic neuritis that is so closely linked to multiple sclerosis and is described in Chapter 20. The first priority is to realize that the patient does not have a classic case of optic neuritis. There are “red flags” (in both the patient history and the examination) that should alert you of this possibility. These include:

HISTORY RED FLAGS

Simultaneous bilateral involvement of the optic nerves

Documented progression beyond a week after onset

Recurrence, especially if this occurs as corticosteroids are being tapered

Presence of other neurologic symptoms of simultaneous onset (aside from local ocular pain)

Presence of an acute illness in the immediate period before the onset of the optic neuritis (e.g., fevers, acute asthma)

Presence of a systemic illness that may cause a secondary optic neuritis

EXAMINATION RED FLAGS

Pupillary findings inconsistent with multiple sclerosis, such as Argyll-Robertson pupils

Proptosis

Anterior uveitis

Ophthalmoplegia

Sensory involvement of the trigeminal nerve

Retinal findings such as periphlebitis, arterial occlusive disease, granulomas, or macular stars

Presence of another cranial nerve sign or another neurologic sign simultaneous in onset to the optic neuritis

Whenever you encounter these red flags, you should expand your differential diagnosis to include several of the entities that are discussed in this chapter, and undertake a directed diagnostic evaluation. However, there is rarely anything specific about the ocular involvement in these forms of inflammatory optic neuropathies that would allow one to make a specific diagnosis. Thus, the systemic and laboratory evaluation are crucial to instituting specific therapy.

SARCOIDOSIS

Sarcoidosis is a multisystem disease of unknown etiology. There are multiple theories about its pathogenesis, including frank infection or allergic responses to organisms that are ubiquitous and typically nonpathogenic, including mycobacterial species.¹ Sarcoid has a predilection for the lungs and for glandular tissue such as the lacrimal, submandibular, and parotid glands.

URGENCY OF EVALUATION

The urgency of evaluation is linked to how long the patient has had visual loss. If the visual loss has been static for many months and optic atrophy is present, then there is less urgency to the evaluation. Conversely, when the visual loss is acute, sarcoid optic neuropathy may respond very rapidly to therapy; thus, rapid evaluation within days may be beneficial.

DIAGNOSIS

There is often nothing about the visual presentation of the case of truly isolated acute sarcoid optic neuritis that reliably distinguishes it from typical optic neuritis. The prolonged course over time, the development of other signs and symptoms, and on occasion, the profound visual improvement with the initiation of systemic corticosteroid therapy (or, conversely, the rebound to steroid taper) may help identify these cases.

Symptoms

Demographics

Sarcoidosis is a worldwide disease that may be seen in all ethnic groups, though in the United States it is of higher incidence in African Americans, with females more often affected than males. The peak incidence is in young adults. Neurologic disease is seen in 5 to 16% of cases, and ophthalmic disease is seen in ~20 to 25% of all patients with sarcoidosis, higher if there is pulmonary disease.1,2

Visual Loss

There are several types of optic neuropathy in sarcoidosis: (1) nonspecific inflammation indistinguishable from idiopathic optic neuritis; (2) infiltration of the optic nerves and/or sheaths, mimicking an optic nerve mass such as a glioma or meningioma; (3) direct compression of the nerve, such as from an orbital granuloma; and (4) parachiasmal involvement. Thus the extent of the visual loss and pattern of the loss may be quite variable, ranging from a small central scotoma noted in one eye, to peripheral constriction, to bitemporal field loss.

Pain

Pain is variable. It is our impression that it is more often seen in cases with uveitis and less frequently in cases with chiasmal and posterior optic nerve involvement.

Signs

Visual Acuity

Depending on the location and the mode of optic nerve involvement, acuity may be completely spared or it may be severely affected.

Visual Field

Depending on the location and mode of optic nerve involvement, the visual field may show central scotomas, peripheral constriction, bitemporal field defects, or if the optic tract is involved, homonymous hemianopsia. Optic nerve sarcoidosis is one of the entities that is suggested by simultaneous optic neuritis and raised intracranial pressure (as are tuberculosis and syphilis, discussed later). In these cases, one may see peripheral field loss and acute central visual loss (Fig. 21–1).

Pupils

If the visual loss is unilateral or asymmetric, one typically sees a relative afferent pupillary defect. If it is bilateral and symmetric, one may not.

Optic Disc

The optic disc may be normal (e.g., retrobulbar involvement) or may be swollen. There may be a granuloma visible on the optic nerve head (Fig. 21–2).

Other Findings

The anterior manifestations of ocular sarcoidosis include conjunctival nodules, keratic precipitates, and iris nodules (Busacca at the border of the iris, Koeppe nodules in the substance of the iris). Other manifestations include uveitis and lacrimal gland enlargement. More posteriorly other signs, such as vitreous opacities, snowballs, or candle wax drippings are seen. In the retina, one may see periphlebitis (Fig. 21–3). This finding is important because, although it may be seen in optic neuritis, it is usually not extensive, and recognizing it in the presence of an ocular or neurologic symptom may be the first real step in diagnosing occult sarcoidosis. Although in some cases the periphlebitis is obvious, the detection of periphlebitis may be aided with a fluorescein angiogram. Choroidal granulomas are not rare (Fig. 21–4), and are seen as deep to the retina. Sarcoid may rarely include a retinal granuloma.³

FIGURE 21–1 Visual field of right eye of patient with presumed sarcoid optic neuropathy with acuity of counting fingers OS and 20/30 OD. The color vision was preserved. This field loss, with color vision preserved and good acuity, is typical of optic perineuritis.

FIGURE 21–2 Optic nerve granuloma in sarcoid optic neuritis. The acuity was 20/20, the granuloma resorbed, and the acuity returned to 20/20 with corticosteroid therapy.

ANCILLARY TESTING

If the patient is known to have sarcoidosis, and develops an optic neuropathy in the course of the already established disease, the diagnosis is usually by inference unless something about the clinical course suggests that sarcoid is not the etiology. In the patient without established sarcoidosis, the diagnosis is more challenging. Often it is suggested by other ocular signs that suggest sarcoid or similar diseases, such as periphlebitis or choroidal granuloma. However, in the patient with no other findings, and only an atypical course for optic neuritis as the red flag, ancillary testing plays a key role.

FIGURE 21–3 Periphlebitis in a patient with optic neuritis. This finding establishes sarcoidosis as a key element in the differential diagnosis.

FIGURE 21–4 Choroidal granuloma in a patient with sarcoidosis.

Neuroimaging

In sarcoid, there are many forms of optic neuropathy. In the case where a granuloma is acting like a mass lesion and compressing the nerve, a lesion may be seen. In cases with infiltrative optic neuropathy, there may be scant, if any, findings. Magnetic resonance imaging (MRI) is the imaging modality of choice in neurosarcoidosis. In some cases, one may see intense enhancement of the optic nerve. The chiasm and or tract may enhance (Fig. 21–5). In other cases, mild enhancement of the optic nerve may not be strongly suggestive of sarcoid, but enhancement of the meninges, particularly at the base of the skull just anterior to the chiasm (an area often overlooked) may suggest sarcoidosis.

FIGURE 21–5 T1-weighted magnetic resonance imaging (MRI) scan with gadolinium showing enhancement of optic tract.

Lumbar Puncture

The hallmark of neurosarcoidosis is lymphocytic pleocytosis. Elevated protein levels may also be seen. A normal spinal fluid does not absolutely rule out that sarcoid is the etiology of the optic neuritis.

Laboratory Tests

Contrary to what is believed by many, neither an abnormal chest x-ray nor an elevated angiotensinconverting enzyme (ACE) level is necessary for diagnosing sarcoid. If one is suspicious of sarcoidosis, an aggressive workup at presentation, including chest x-ray, ACE, gallium scan (Fig. 21–6), purified protein derivative (PPD), anergy panel, pulmonary function tests, and 24-hour urine calcium, may help to establish the diagnosis, in addition to the previously mentioned MRI scanning and lumbar puncture.

Pathological Diagnosis

The typical pathology is the noncaseating granuloma, although rarely one may encounter caseation. In general, it is wise to seek a tissue diagnosis at onset, as well as to stage the patient for the extent of the systemic disease process. The tissue diagnosis is best established when one biopsies obvious lesions, such as a lacrimal or conjunctival nodule, or when the gallium scan points out abnormal tissue that may be biopsied.

If the patient has been on steroids for a period of time before the diagnosis is entertained, abnormal laboratory tests or biopsy may be “normalized” by the steroid therapy, and one may have to repeat the evaluation again 2 to 3 months after the steroids have been weaned.

FIGURE 21–6 Positive gallium scan in a patient with sarcoid optic neuritis, demonstrating uptake in both hila, the lacrimal glands, one parotid gland, and one submandibular gland.

THERAPY

Systemic sarcoidosis that involves the nervous system is typically treated with corticosteroids; if this fails, other immunomodulatory agents such as methotrexate, azathioprine, cyclophosphamide, cyclosporine, and thalidomide may be employed.

FOLLOW-UP AND REFERRAL

Sarcoid optic neuropathy is an uncommon disease best cared for by those who have experience with it. If the diagnosis is proven, or strongly suspected, we recommend referral to a neuroophthalmologist and an internal medicine subspecialist familiar with the systemic illness to direct the evaluation, staging, and therapy of the disease process.

TUBERCULOSIS

Tuberculosis is an infection caused by Mycobacterium tuberculosis. Unfortunately, tuberculosis (TB) is enjoying a worldwide resurgence, in part due to the prevalence of acquired immune deficiency syndrome (AIDS). Tuberculous optic neuritis is a rare disease, with little mentioned in the literature in the past 30 years. Unfortunately, this means that there are few physicians who have extensive experience with this disorder. This disease must be considered in anyone with an atypical optic neuritis, particularly if one is contemplating starting corticosteroid therapy (which could reactivate undiagnosed tuberculosis).