Atypical Optic Neuritis

Warren, Floyd A. MD

doi: 10.1097/WNO.0000000000000180
Virtual Issue

NYU Langone Medical Center, New York, New York.

Address correspondence to Floyd Warren, MD, NYU Langone Medical Center, 530 First Avenue, Suite 3B, New York, NY 10016; E-mail:

Article Outline

Optic neuritis of adulthood is most commonly seen in younger individuals, aged 15–45 years. Pediatric optic neuritis has a different clinical presentation and prognosis and will not be discussed here. The ONTT (Optic Neuritis Treatment Trial) demonstrated that patients with typical optic neuritis present with subacute unilateral loss of visual acuity, acquired dyschromatopsia and visual field loss. Optic neuritis is associated with pain in approximately 90% of patients, with pain preceding the visual loss in approximately 40% of cases. Patients often experience pain with eye movements. Clinical examination shows a relative afferent pupillary defect in the affected eye unless there has been prior damage to the contralateral optic nerve for any reason. Funduscopic evaluation reveals a normal optic disc, macula, and vessels in two thirds of cases and optic disc swelling in one third. There may be minimal cells in the vitreous overlong the optic disc. Vision typically decreases over a week or 2, stabilizes for a similar period and then after 2–4 weeks, it begins to improve. Ninety percent of patients make an excellent recovery with minimal deficits on examination, although a high percentage have subjective visual complaints. A historical perspective on optic neuritis was published by Volpe (1).

What should alert clinicians to the possibility that they are dealing with atypical optic neuritis? Bilateral simultaneous (2–5) or rapidly sequential bilateral visual loss has been reported in many of the atypical cases (6). Frequently, significant disc swelling has been observed (2), and there may be evidence of concomitant uveitis and/or retinal findings. As the ONTT reported and many of the atypical optic neuritis cases demonstrated, no light perception vision suggests non-MS-related optic neuritis (4–7). One's suspicions should also be raised by nonneurological symptomatology either simultaneously with the visual loss (3) or having occurred just before the episode or closely following it. Although uncommon, atypical optic neuritis can occur in patients with systemic lupus erythematosus (8), inflammatory bowel disease (9), or rheumatoid arthritis (10). Atypical optic neuritis can be seen in the setting of infections either directly or as a parainfectious process (2,3,7,10–17). Although the latter generally has a good prognosis, this is not always the case (3,7,11). Other inflammatory and hematologic entities can have associated optic neuritis (6,18).

Neuromyelitis optica or Devic disease (19–21) is possibly the neuroophthalmologists' greatest concern when dealing with isolated optic neuritis, as both the prognosis and treatment modalities are very different (21–24) from MS-related optic neuritis (25–27). Whether all optic neuritis patients should be tested for neuromyelitis optica (NMO) (aquaporin-4) antibodies remains controversial (28,29) but there is agreement that patients who have poor recovery of visual acuity or significant residual visual field deficit should be tested even if they lack other neurological signs of NMO (28).

Several articles have looked at the magnetic resonance imaging characteristics of NMO-related optic neuritis, trying to distinguish it from MS-related optic neuritis. Although the lesions tend to be more longitudinally extensive in NMO optic neuritis (30,31) and have greater posterior optic nerve involvement, there is no pathognomonic neuroimaging finding, Certainly, bilateral optic nerve or chiasmal involvement is very suggestive of NMO-related disease, especially without other signs or symptoms, although chiasmal involvement with MS-related demyelination has been reported (31). Brain MRI may show lesions in the posterior fossa, particularly in the area postrema, in a pattern not characteristic of MS (32).

A potential mimicker of optic neuritis is optic perineuritis (13,16,33). Although this is often considered as part of the spectrum of idiopathic orbital inflammatory disease, it can occur with specific inflammatory, infectious, or neoplastic etiologies (13,34). Patients with optic perineuritis may present without obvious (or any) orbital signs, with isolated eye pain, visual loss with a relative afferent pupillary defect, and an otherwise normal examination, that is, “typical” optic neuritis. Orbital imaging is essential to establishing the diagnosis because the treatment is different (oral steroids) from demyelinating optic neuritis and prognosis generally excellent.

As sometimes a cigar is just a cigar, most optic neuritis is “just” optic neuritis. The clinician should be suspicious of atypical optic neuritis if the patient presents with nonneurologic symptoms, especially rheumatologic or infectious, has ocular findings beyond monocular visual loss, with a relative afferent puillary defect and optic disc edema and has poor recovery of visual acuity and visual field loss. Atypical optic neuritis mandates comprehensive patient evaluation, including hematologic, spinal fluid, and neuroimaging studies.

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