Optic Perineuritis

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Article initiated by:

Bayan Al Othman, MD, Connor Dugan, BS

All contributors:

Andrew Go Lee, MD, Ashwini Kini, MD, Landon Meekins, M.D., Nagham Al-Zubidi, MD, Bayan Al Othman, MD, Mark Goerlitz-Jessen, MD

Assigned editor:

Bayan Al Othman, MD

Review:

Assigned status Update Pending

 by Bayan Al Othman, MD on May 17, 2024.

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Contributing Editors:	add

Summary

Optic perineuritis (OPN) is a form of orbital inflammatory disease in which the optic nerve sheath becomes inflamed secondary to one of a variety of potential etiologies. It typically presents as eye pain with variable visual complaints. It is critical to distinguish optic perineuritis from optic neuritis due to the therapeutic and prognostic differences between the two diseases. Critical studies include MRI brain and orbits with and without gadolinium contrast, serologic testing, and possible lumbar puncture. OPN is typically very responsive to corticosteroid therapy but, unlike optic neuritis, is not self-limited (i.e. does not resolve without therapy). Initial treatment typically consists of immunosuppression in the form of steroids, which should be tapered very slowly to prevent recurrence of disease.

Disease Entity

• Other optic neuritis – ICD10: H46.8
• Other disorders of optic nerve, not elsewhere classified – ICD10: H47.099

Disease

Optic perineuritis (OPN) is an uncommon form of idiopathic orbital inflammatory disease, in which the specific target tissue is the optic nerve sheath. Optic perineuritis is a distinct entity from demyelinating optic neuritis (see: Demyelinating Optic Neuritis). OPN is comprised of a spectrum of diseases that can be divided into two categories: primary and secondary. Primary is idiopathic in nature and secondary is considered to be a part of an identifiable systemic condition.

Optic nerve sheath inflammation is accompanied by eye pain as well as varying levels of optic nerve dysfunction (decreased vision, decreased color vision, visual field changes, and relative afferent pupillary defect). Less frequently, orbital signs (proptosis, decreased motility etc.) may be present. It is important to distinguish OPN from optic neuritis due to prognostic and therapeutic implications.

Epidemiology

The mean age of presentation in several case series is between 40 and 60 years. Acute and subacute inflammation of the optic nerve and its sheath: clinical features in Chinese patients. However, there is widespread range in the age of affected patients with reported cases in patients as young as 15 and as old as 85. Some case series have shown a predilection in women, though no definitive gender disparity has been established.

Etiology

Most cases are idiopathic (idiopathic optic perineuritis). However, it may be a manifestation of a systemic disorder including but not limited to the following: sarcoidosis, IgG4-related disease, granulomatosis with polyangiitis (GPA), giant-cell arteritis (GCA), Behcet’s disease, systemic lupus erythematosus,1 inflammatory bowel disease, syphilis, tuberculosis, herpes simplex virus, herpes zoster virus, leukemia, other viral encephalidities, and primary or metastatic malignancy. It has also been documented to present simultaneously with neuroretinitis.

History

Optic perineuritis was first described by Edmunds and Lawford in 1883. They reported a histopathologic specimen of an optic nerve with inflammatory infiltration loosely organized around the perimeter. In the past OPN was described an optic neuropathy with evidence of optic disc swelling, but no optic nerve dysfunction with normal intracranial pressure (ICP). The advent of modern neuroimaging of the sheath (magnetic resonance imaging) has revised the clinical and radiographic features of OPN. A major case series describing OPN was performed by Purvin et al., which helped characterize OPN as a syndrome that includes a number of possible etiologies.

Risk Factors

OPN appears to have a higher incidence in women. The average age of patients with optic neuritis seems to be around 40-45 years of age, which may help to distinguish from demyelinating optic neuritis (peak manifestation from 15-50). Sarcoidosis, IgG4 disease and MOG have been associated with a radiographic and clinical appearance similar to idiopathic OPN.

General Pathology

Histologic evaluations of affected optic nerves have revealed thickening of the perioptic meninges with inflammatory infiltration and fibrosis. The inflammatory infiltrate is composed of polymorphonuclear leukocytes within the meninges and stages of lymphocyte infiltration of the sheath and the adjacent optic nerve parenchyma. Cases of granulomatous inflammation and focal necrosis have also been identified. Biopsied and excised nerves of patients with OPN who experienced vision loss have demonstrated optic nerve demyelination or vasculitic changes causing infarction.

Pathophysiology

The pathophysiology of OPN may reflect the underlying cause and most cases remain idiopathic. Although the immune-mediated inflammation is primarily within the nerve sheath, axons of the optic nerve may also be affected to varying degrees. The variable degree and location of inflammation contribute to the range of symptoms and exam findings.

Diagnosis

Signs/Symptoms

The clinical presentation of OPN may mimic optic neuritis. The majority of patients present with acute visual loss, eye pain, or both. Like optic neuritis, the eye pain may be exacerbated by eye movement but the pain in OPN may be more severe or long lasting than in typical optic neuritis. The visual loss in OPN is variable and may range from none to severe. Patients may describe visual blurring, dimming, “spots” in vision, or splotches.

Physical examination

Optic disc edema is present in a majority of patients with OPN. Visual acuity is typically decreased (but may be normal) with varying degrees of visual acuity and visual field deficit described in different case studies. However, the vision loss in OPN appears to be more progressive than that of demyelinating optic neuritis, with the loss of vision progressing over several weeks. Visual field deficits can vary and include arcuate defects, paracentral or central scotomas, peripheral island, and altitudinal defects. Unlike isolated optic neuritis, the orbital and optic nerve sheath involvement in OPN may result in other orbital signs and symptoms including ptosis, ophthalmoplegia, and exophthalmos. Rarely reported intraocular findings in OPN include retinal necrosis, scleritis, and episcleritis. OPN is typically unilateral, but bilateral cases have also been reported in the literature.

Clinical diagnosis

OPN is often clinically difficult to distinguish from optic neuritis and, in some cases, from other orbital inflammatory or infectious conditions due to the overlap in symptomatology. However, it is important to identify which disease a patient has due to critical therapeutic and prognostic implications.

Clinical similarities to optic neuritis include: decreased visual acuity, possible presence of an RAPD, visual field loss, and dyschromatopsia. However, there are often clinical differences between OPN and optic neuritis. These include: faster onset in optic neuritis (days) compared to OPN (weeks). Central vision is more often spared in OPN, which also leads to less dyschromatopsia and a less frequent or subtler RAPD.

Diagnostic procedures

The diagnosis of OPN is typically based on a combination of clinical and radiographic findings. Gadolinium-enhanced, fat-saturated T1 magnetic resonance imaging (MRI) of the orbits is the key to diagnosis of OPN. Compared to the enhancement of the nerve seen in typical optic neuritis, the MRI in OPN usually shows perioptic enhancement around the optic nerve sheath. This perioptic enhancement may appear as “tram-tracks” in the axial view, and “doughnut” in the coronal view. However, it is important to note that this is not specific and the “tram-track” sign can be present in any optic nerve sheath pathology, such as optic nerve sheath meningiomas, sarcoidosis, leukemia, etc. Care must be taken to not mistake normal dural enhancement from vascular supply for enhancement secondary to inflammation. Computed tomography imaging is inadequate for diagnosis or exclusion of OPN due to inferior soft tissue resolution compared to MRI. B-scan ultrasound has not been used, classically; however, reports indicate it may be useful in select cases.

Rarely, an optic nerve biopsy may be necessary in order to confirm the diagnosis. This may be particularly useful in patients non-responsive to corticosteroids with no defining underlying etiology for the optic perineuritis to confirm the etiology. If a biopsy has been performed, it typically shows inflammatory infiltrate into the dural sheath, or possibly perineural fibrosis tissue.20 No specific lab tests are diagnostic for OPN.

Lumbar puncture should be performed to rule out central nervous system infection and malignancy if there is no clear underlying condition.6 In addition to serologies described below, chest radiography may be employed as part of the work-up for sarcoidosis.

Laboratory test

If a patient does not have a clear underlying cause for perineuritis, systemic work-up should be performed. Serology testing for syphilis, angiotensin-converting enzyme, ANCA, and IgG4 are typically the first tests obtained in addition to the aforementioned imaging and lumbar puncture. However, a good history and clinical judgement should be used to guide additional serologic work-up given the vast potential etiologies of optic perineuritis (see above).

Differential diagnosis

• Optic neuritis (e.g., demyelinating, MOG, other)
• Orbital inflammatory syndrome (e.g., idiopathic, IgG4, sarcoidosis, granulomatous)
• Infection (e.g., tuberculosis, syphilis, Lyme, Bartonella)
• Neoplasm (e.g., meningioma, leukemia, lymphoma, metastasis)
• Posterior scleritis, secondary disc edema associated with uveitis

Associated Conditions

OPN has recently been found to be a presenting symptom for a wide variety of clinical conditions. Cases have been reported in the literature of OPN being the presenting sign for tuberculosis, B-cell ALL, giant cell arteritis, syphilis and sarcoidosis, polyangiitis with granulomatosis, inflammatory bowel disease, systemic lupus erythematosus, and Behçet disease. If no clear associated condition is present, serum could be tested for anti-neutrophilic cytoplasmic antibodies (ANCA), syphilis, and IgG4.

Management

General treatment

Initial treatment for OPN generally includes high-doses of systemic corticosteroids. The dosage of steroids may vary depending on the frequency of attacks, with higher frequency requiring a higher dosage. Likewise, higher rates of recurrence were seen in a case study which used 30-40 mg/day versus a higher dosage of 60-80 mg/day. The response to steroids can be rapid and dramatic but the symptoms may recur quickly upon tapering of steroids, requiring a long slow taper to minimize risk of recurrence.

There has been a case reported of spontaneous resolution of OPN without any treatment. In the initial case study describing OPN by Purvin, et al, 2 patients were treated successfully with indomethacin as opposed to corticosteroids. There are also reports of treatment with radiation therapy and immunosuppressants, namely azathioprine, in refractory disease. Nevertheless, corticosteroids remain the mainstay of therapy.

Relapse of symptoms after cessation of steroid therapy is more common in OPN than optic neuritis. Also, recovery in OPN is often much quicker with patients experiencing relief of pain and visual symptoms within hours up to a day after treated is initiated. If a patient recently treated for optic neuritis relapses after therapy, consideration should be given to the possibility of a misdiagnosis and OPN may need to be considered.

Comorbidities predisposing patients to OPN should be treated in an evidence-based and multidisciplinary fashion.

Medical follow up

Close follow-up is important to ensure patients do not experience relapse and that the prescribed steroid therapy has been adequate. Snellen acuity, visual field testing, color vision, pupillary, and repeat funduscopic exams should be performed to monitor optic nerve function and the presence of residual deficits. Repeat imaging is generally unnecessary unless symptoms persist despite treatment.

Complications

Complications of OPN tend to result from treatment of the disease with high-dose corticosteroids, or the conditions that tend to be associated with the disease.

Prognosis

OPN typically has a relatively good prognosis. Unlike demyelinating optic neuritis, there is no known association between development of OPN and multiple sclerosis. Visual outcome tends to be excellent in patients with optic perineuritis, with a majority of patients in clinical case studies returning to 20/20 or better. However, complete vision loss may result if the diagnosis is not recognized and treatment is not initiated promptly. Prognosis tends to be poorer in patients who have delayed time from vision loss to onset of steroid initiation, as well as patients with a high frequency of attacks.