Article, Ophthalmology

Ophthalmic diagnoses in the ED: optic neuritis

Diagnostics

Ophthalmic diagnoses in the ED: optic neuritis

Carl A. Germann MDa,*, Michael R. Baumann MDa, Sirus Hamzavi MDb

aDepartment of Emergency Medicine, Maine Medical Center, Portland, ME, USA

bDepartment of Opthalmology, Central Maine Medical Center, Lewiston, ME, USA

Received 17 January 2007; accepted 18 January 2007

Abstract Optic neuritis is the most common cause of decreased vision due to optic nerve dysfunction in patients who are 20 to 40 years of age. Optic neuritis, or inflammation of the optic nerve, is primarily due to idiopathic demyelination. Demyelinative lesions seen in optic neuritis are not unlike those seen in plaque associated with Multiple sclerosis. In fact, acute inflammatory demyelination of the optic nerve commonly occurs as an initial manifestation of multiple sclerosis. Key features of optic neuritis include a Vision loss occurring over 1 to 10 days, color vision impairment, eye pain with motility, and an afferent pupillary defect. This significant diagnosis can be challenging to an emergency physician as it is relatively infrequently observed.

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Introduction

In the United States, the annual incidence of optic neuritis in a predominately white community is approximately 5 per 100,000 per year, whereas the prevalence is 115 per 100,000 [1]. Most cases occur in patients between 15 and 45 years old, with women affected more frequently than men.

Most cases are due to inflammatory demyelination of the optic nerve. The pathophysiology leading to the demyelin- ation is most often idiopathic. Occasionally, optic neuritis may be due to an infectious process involving the orbits or paranasal sinuses. Optic neuritis caused by inflammatory demyelination carries a strong association with multiple sclerosis (MS), but cases may occur in isolation.

The diagnosis of this disease is made based on history and Physical exam findings. However, magnetic resonance imaging (MRI) may yield prognostic information in terms of the patient’s future risk for development of MS. Despite a

* Corresponding author. Maine Medical Center, Portland, Maine 04102, USA. Tel.: +1 207 774 7333.

E-mail address: [email protected] (C.A. Germann).

large amount of recent research regarding the therapy for optic neuritis, the treatment remains controversial.

Case example

A 28-year-old woman arrived at the emergency depart- ment (ED) complaining of a 3-day history of progressive headache, eye pain, and unilateral Blurred vision. She denied a history of Chronic headache and stated that she had previously been in good health. There is no history of recent trauma.

On physical examination, the patient was alert and oriented. Her vital signs were normal. The visual acuity was tested at 20/20 on the right side and 20/200 on the left. Cranial nerves II through XII were normal. Results of her fundoscopic examination was normal bilaterally. She had mild discomfort with extraocular muscle movements. The patient reported that red and orange colors appeared bless bright,Q and an afferent pupillary defect (APD) was present on examination of the left eye. Results of her neurologic examination did not demonstrate any other focal lesions.

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Pathophysiology and clinical manifestations

Optic neuritis represents an inflammatory and demyelin- ating condition of the optic nerve. The most common form arises from idiopathic demyelination of the nerve. This degeneration of the optic nerve represents the most common cause of optic nerve disease. Pathologically, the nerve is surrounded by inflammatory cells initiating swelling and fragmentation of the nerve tissue. Further degeneration occurs as macrophages phagocytize myelin breakdown products [2]. The other, less common causes of optic nerve disease, or optic neuropathy, arise secondary to various systemic illnesses, toxins, and trauma. Diabetes mellitus, systemic lupus erythematosis, temporal arteritis, tuberculo- sis, encephalitis, and certain medicines have been associated with optic neuropathy.

Fig. 1 Afferent pupillary defect.

On presentation, the visual acuity can vary from 20/20 to no light perception [2]. Loss of vision is frequently unilateral, although Visual loss may be binocular, particu- larly in children. Binocular vision loss should instigate a search for other causes, with optic neuritis as the diagnosis of exclusion. The natural history of a typical case of optic neuritis is for visual acuity to gradually decline and reach its poorest level within 10 days. Vision gradually improves over the next several weeks with good return of vision in most patients [2]. A good prognosis for visual recovery is expected with 95% of patients achieving final visual acuity of 20/40 or better [3].

If checked in the ED, color vision and contrast sensitivity are affected in almost all cases. As in MS, degeneration of the myelin sheath impairs nerve transmission and thus distorts perception of color by diminishing input from the cone cells of the retina. Color differentiation and perception is commonly affected to a greater degree than visual acuity and can help hone the differential if checked in patients with eye problems.

Mild pain in or around the eye is present in more than 90% of patients. Pain is typically mild and characterized as a soreness, ache, or general discomfort. This discomfort may begin days to weeks before the onset of visual problems. Patients with optic neuritis may also develop pain in or about the affected eye that is worsened by eye movement. Eye discomfort generally decreases over a few days to 2 weeks. Symptom improvement most likely correlates with resolution of the inflammation and associated conduction block [4].

An APD is almost always present because of the loss of fibers in the afferent limb of the light reflex arc. The affected eye perceives less light as a result of the optic nerve dysfunction. The brain receives the message of less light and the result is less constriction when light is shined into the involved eye than in the normal one. The swinging flashlight test is reportedly abnormal in more than 90% of patients with optic neuritis [5]. When each eye is illuminated in succession, there is a brisk constriction of both pupils when light is applied to the normal eye, followed by a lack of response or dilation of the pupils when light is applied to the affected eye (Fig. 1).

Optic neuritis is a common presenting event in patients who are eventually diagnosed with MS. Approximately 30% of patients presenting with acute optic neuritis will develop MS with in 5 years [6]. The most important predictor of subsequent development of MS is the presence of white matter lesions on MRI.

Diagnosis

Optic neuritis is generally a clinical diagnosis based on history and physical examination. In cases with typical clinical symptoms, laboratory testing is unlikely to be revealing [7,8]. Symptoms often include a reduced visual

Fig. 2 Papillitis.

acuity and color perception, ocular pain, and APD in the affected eye [9-12]. The first 2 symptoms can be tested by using a standard eye chart and pseudoisochromatic plates.

Most cases of optic neuritis are retrobulbar and the fundoscopic examination will appear normal [13]. In one third of cases, inflammation will involve the optic disc (papillitis) resulting in mild swelling on fundoscopic exam (Fig. 2). Severe edema or disc hemorrhage is infrequently seen in optic neuritis and other diagnoses should be explored. These diagnoses may include malignant hyper- tension, anterior ischemic optic neuropathy, Lyme disease, or papilledema from Intracranial injury.

Although not required for diagnosis of optic neuritis, imaging can be helpful in assessing risk for the development of MS. Computed tomography is relatively insensitive for the detection of optic nerve inflammation; in contrast, MRI can show optic nerve abnormalities in most cases, although MRI in typical optic neuritis is unlikely to reveal an alternative reason for visual dysfunction [7,14-16]. In approximately 50% of patients with optic neuritis, brain MRI will reveal white matter lesions [10]. In the Optic Nerve Treatment Trial, the 5-year risk of developing MS was 16% in patients with normal brain MRI findings, 37% with 1 to 2 lesions, and 51% with 3 or more lesions [6]. Therefore, in patients with suspected or known optic neuritis, MRI of the brain should be performed to assess the presence of white matter lesions and assess risk for the development of MS and guide therapy [6,17].

Treatment

There is no known cure for optic neuritis. Much of the current understanding of the treatment comes from the Optic Neuritis Treatment Trial (ONTT), which was a multicenter trial composed of 457 patients with optic neuritis. The primary objective of this study was to assess the benefit of corticoSteroid treatment of optic neuritis. Numerous follow-

up studies were performed to investigate the potential benefit of steroids for treatment of optic neuritis and prevention of MS.

In the ONTT, patients were randomly treated with oral prednisone, intravenous methylprednisolone followed by oral prednisone, or placebo [8]. The ONTT reported that intravenous methylprednisolone treatment hastened the recovery of visual function, but did not affect long-term visual outcome after 6 months to 10 years when compared to placebo or oral prednisone [3,18]. This benefit was greatest within the first 15 days [18]. The authors also reported an increased risk of recurrence of optic neuritis in those patients treated with oral prednisone [6,19]. Other randomized studies have also demonstrated that use of high- dose oral methylprednisolone may hasten the recovery of visual symptoms [20].

Intravenous methylprednisolone may have a dual benefit in those patients with white matter lesions on MRI of the brain by delaying the onset of MS symptoms. However, methylprednisolone does not appear to alter the risk of development or degree of disability [6]. The ONTT concluded that treatment with a 3-day course of intravenous methylprednisolone reduced the rate of development of MS over a 2-year period [19]. The 5-year follow-up of this same patient cohort revealed no significant differences among treatment groups in the development of MS [6]. For this reason, some neurologists will consider intravenous steroids for any attack of optic neuritis, although no treatment may also be an acceptable course of action. It should be clear that corticosteroids appear to hasten the recovery of vision, but have not been shown to improve final visual outcome and may decrease the symptom onset of MS for only a finite period [3,7,21].

In addition to the ONTT data, a meta-analysis of numerous placebo-controlled trials using corticosteroids demonstrated that no long-term improvement was achieved [22]. In 2000, the Quality Standards Subcommittee of the American Academy of Neurology recommended that bthe decision to use these medications to speed recovery but not to improve ultimate visual outcome should therefore be based on other non evidence-based factors such as quality of life, risk to the patient, visual function in the fellow eye, or other factors that the clinician deems appropriateQ [23]. When treatment is initiated, the preferred regimen (as suggested by the ONTT) is 1 g of methylprednisolone per day (IV) for 3 days followed by oral prednisone 1 mg/kg per day for 11 days [24]. Local Treatment decisions should be decided in collaboration with the consulting ophthalmolo- gist and neurologist.

Recent randomized trials have supported the use of interferon therapy after the development of acute demye- linating optic neuritis in patients with white matter lesions on MRI of the brain. Treatment with interferon demonstrat- ed a reduced rate of accumulation of new lesions on MRI. However, the potential long-term benefit of this treatment of MS is unknown [25-28].

After making the diagnosis of optic neuritis, it is appropriate to discuss the association with MS with the patient and arrange follow-up with a neurologist. The decision of when to perform an MRI should be made in conjunction with this consultant. For patients at higher risk of developing MS (those with 2 or more white matter lesions on MRI), consideration should be made to treat with steroids (intravenous methylprednisolone for 3 days followed by oral prednisone for 11 days) and/or interferon (weekly). Diagno- sis, treatment and follow-up plans should be made in collaboration with a neurologist and ophthalmologist.

Key points

    • Optic neuritis is a clinical diagnosis that often includes eye pain, a relatively abrupt vision and color differentiation loss, and an afferent papillary defect.
    • Intravenous steroids have been shown to speed the

recovery of vision without affecting the final visual outcome.

    • Steroids may also decrease the symptom onset of MS

over the first 2 to 3 years after optic neuritis.

    • Brain MRI is the most useful predictor of subsequent development of MS.

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