Etiology is crucial to substantive treatment.
Optic neuritis and neuropathies can present in many ways and have a wide variety of potential etiologies. Generally indicative of a current or previous inflammatory or ischemic state of the optic nerve, signs of optic neuritis may include optic disc swelling, a sign of active inflammation, or optic atrophy, signifying a previous event. But it is not always that simple, because the physical appearance of the prelaminar optic nerve (ie, the part of the nerve we examine) can vary depending on the underlying condition, the stage and severity of the disease, and other factors. The thought process of sorting through these factors and differentials during an examination, especially in the moment when it is time to alert your patient of the findings and next steps, can be daunting. Is it serious, meaning vision or life threatening? Is it urgent? Or is it long standing and a nonissue? Causes include toxicity, vasculopathy, demyelination, and tumors.
Optic neuritis represents an active inflammatory process affecting the optic nerve anywhere along its path anterior to the optic chiasm. Strictly speaking, the etiology is inflammatory in nature, with possibilities ranging from toxicity to demyelination or other autoimmune disease. Optic neuropathy, on the other hand, is typically vascular in nature.1 Clearly, there is overlap between definitions and differentials. Both optic neuritis and optic neuropathy can present similarly in their early stages, and until the specific cause is parsed out, they can be managed the same way. As such, these terms may be used interchangeably in the following paragraphs.
Optic neuritis can occur in one eye or in both, and in either case, it can represent a primary ocular disease or an underlying systemic condition. As with many ophthalmic findings, bilaterality most often represents a systemic etiology. Presenting as eventual optic atrophy with disc pallor and generalized loss of sensitivity, bilateral optic neuritis may be secondary to toxicity and autoimmune disease or may be genetically inherited, as noted in Table 1.2-3
Differentiated from optic neuritis, active bilateral disc edema should be determined as an emergency, such as with a hypertensive crisis; urgent, such as with a compressive lesion or hydrocephalus; or nonurgent. A common nonurgent cause includes idiopathic intracranial hypertension (IIHTN). Those not associated with critically elevated blood pressure level are often initially referred for brain imaging to rule out a space-occupying mass. Another important step for these cases is differentiating them from those conditions that do not require expensive and invasive testing, such as with optic disc drusen and anatomically crowded discs.
In the case of suspected unilateral optic neuritis or neuropathy, there is also a possibility of emergency or urgency, and although the condition may have an underlying systemic etiology, the focus is usually more on steps to save vision. A summary of possible causes is listed in Table 2,1,4-8 noting that many conditions occurring in one eye could also occur in both.
The questions of “What is this, and what do I do next?” can be answered initially with the patient’s history and examination, particularly of the optic nerve itself. What age is the patient? Are there existing conditions that put the patient at risk for vascular insult, toxicity, or inflammatory manifestations? Is there acuity loss and/or an afferent pupillary defect? Is the disc elevated or pale? If elevated, is it edematous? Are there associated vascular findings such as disc tortuosity or adjacent hemorrhages? Or does the nerve look normal and healthy? As illustrated by the examples in Figure 1, there are many faces of optic neuritis. All 3 patients were ultimately diagnosed with multiple sclerosis (MS); however, this same concept could be applied to many underlying etiologies of optic neuritis. Ultimately, this information can be applied together to determine the first step forward. In-office ancillary testing can, of course, be useful to further guide management plans.
Unilateral optic neuritis can be a sign of inflammation, infection, toxicity, vasculopathy, or demyelination, allowing some overlap with those causing bilateral findings. The patient’s age can be a fundamental place to start as you develop a pathway for diagnosis and management. Figure 2 illustrates appropriate initial suspicions, particularly when no other risk factors are present.9 Pairing age with known comorbidities, and a series of questions looking for uninvestigated symptoms and recent environmental exposures (eg, travel, insect bite, vaccination), a tailored approach can be obtained.
Although the possibilities can be overwhelming, taking the approach of ruling out the most urgent conditions first is critical. Arteritic ischemic optic neuropathy (AION) caused by giant cell arteritis (GCA) should be suspected in any patient older than 55 years (some say patients younger than 55 years) with painless and sudden vision loss. These patients typically have severely reduced acuity as poor as light perception only and an afferent pupillary defect along with a pale, swollen optic disc. Permanent vision loss will occur in up to 30% of these patients, and vision loss occurs in the contralateral eye within 1 week in up to 50% of patients. Notably, up to 50% of patients experiencing GCA also have polymyalgia rheumatica, which can serve as a diagnostic clue. Alternatively, GCA can manifest as an otherwise unexplained central retinal artery occlusion, posterior ION, or an extraocular muscle palsy.10-12
The most common cause of isolated unilateral optic neuritis or neuropathy in middle-aged adults is MS.13-15 Neuromyelitis optica (NMO) is less common, only accounting for 2% of demyelinating disease in this country; however, it is more serious and has a different treatment approach. Earlier differentiation is critical for the best prognosis.16,17
Going beyond Snellen visual acuity in evaluating visual function of a patient with suspected optic neuritis can be revealing of a problem and may prompt further testing. Reduced contrast sensitivity, abnormal color vision, or visual field loss can suggest subclinical damage. Contrast sensitivity and color vision are both known to be reduced in the affected eye of optic neuritis in many cases when vision is 20/20. Threshold visual field testing can also be illuminating, often revealing visual dysfunction missed by acuities. Threshold visual field loss such as enlarged blind spots, central defects, or generalized depressions can be correlated with other findings to point to causes.
Although initially swollen optic nerves, regardless of cause, often cause an enlarged blind spot, their underlying etiology will soon determine visual field pattern. For example, toxic and metabolic optic neuropathies often lead to central or cecocentral defects. Demyelinating optic neuritis most commonly leads to a central defect, in from MS, whereas patients with NMO spectrum disorder often present with central, noncentral, or altitudinal defects. As it relates directly to the vascular pattern of the posterior ciliary nerve which is affected, nonarteritic ION (NAION) presents initially with an altitudinal defect. However, as the retinal ganglion cells of the macula become atrophied as a result, a central defect or generalized depression can ensue.17
Optical coherence tomography (OCT) results such as inner retinal thickening (in the case of active inflammation) or thinning (in the case of atrophy following a disease process) can help to determine both etiology and stage of disease. Patterns of inner retinal loss, whether it be impact to the retinal nerve fiber layer around the nerve or the ganglion cell complex at the macula, can further differentiate etiology. Rapidity of tissue loss can be quite telling as well. Although many optic neuropathies, if left unmanaged, will ultimately result in a similarly poor clinical appearance, the rate at which the change occurs is often very different. This is true for physical appearance of the optic nerve, visual field loss, and changes in retinal ganglion cells; however, the OCT is unique in its ability to quantify and track microscopic change. Optic neuritis from a demyelinating disease or NAION, for example, will likely lead to dramatic thinning in the macular region of the ganglion cell layer after just 1 to 2 months, whereas glaucomatous optic neuropathy or that from a compressive lesion may show the same change over years. In both cases, disease activity and severity can determine rate of change. Furthermore, conditions that are recurrent, such as optic neuritis from MS, can add the insult of cumulative thinning to an already injured retina, complicating the clinical interpretation.18-21
Retinal electrodiagnostics can also add to the clinical picture, with visual evoked potential (VEP) often revealing reduced amplitude and increased latency. These can be useful objective data when the optic nerve itself appears healthy or when there is doubt of normalcy. Although VEP abnormalities are not specific for optic neuritis, they are sensitive and can be paired with electroretinogram to differentiate optic nerve disease from retinal conditions.
Once urgent causes are ruled out and in-office testing has had a chance to delineate, sorting through the differentials can move on to laboratory testing and brain imaging. In any case of unexplained optic neuritis, brain imaging is appropriate. An MRI with contrast of the brain and orbits can be ordered to rule out a space-occupying mass and is often a fundamental step in determining urgency on the road of differentials. Fluid-attenuated inversion recovery (FLAIR) is a technique used by the radiologist to look for demyelinating conditions and should be specified if desired. Chest x-ray is indicated for ruling out sarcoidosis. Common laboratory tests are summarized in Table 3.1,21,22