Chronic relapsing inflammatory optic neuropathy
|Chronic relapsing inflammatory optic neuropathy|
|Other names: Chronic relapsing inflammatory optic neuritis|
|a,b)Automated perimetry at index event showing field defects in both eyes|
Chronic relapsing inflammatory optic neuropathy (CRION) is a form of recurrent optic neuritis that is steroid responsive. Patients typically present with pain associated with visual loss. CRION is a diagnosis of exclusion, and other demyelinating, autoimmune, and systemic causes should be ruled out. Early recognition is crucial given risks for severe visual loss and because it is treatable with immunosuppressive treatment such as steroids. Relapse that occurs after reducing or stopping steroids is a characteristic feature. 
Signs and symptoms
Pain, visual loss, relapse, and steroid response are typical of CRION. Ocular pain is typical, although there are some cases with no reported pain. Bilateral severe visual loss (simultaneous or sequential) usually occurs, but there are reports of unilateral visual loss. Patients can have an associated relative afferent pupillary defect. CRION is associated with at least one relapse, and up to 18 relapses have been reported in an individual. Interval between episodes can range from days to over a decade. Symptoms will improve with corticosteroids, and recurrence characteristically occurs after reducing or stopping steroids.
As of 2013, the etiology remained unknown. Given that CRION is responsive to immunosuppressive treatment, it may be immune-mediated. CRION has been classified as an autoimmune process but this description is not established with certainty and there is no known associated autoimmune antibody. 
As of 2019, the correlation between CRION and antiMOG associated encephalomyelitis is so high that now CRION is considered the most common phenotype related to myelin oligodendrocyte glycoprotein antibodies
Diagnosis requires exclusion of other neurological, ophthalmological, and systemic conditions. Any cause of optic neuropathy should be ruled out, including demyelinating (multiple sclerosis, and neuromyelitis optica) and systemic disease (diabetic, toxic, nutritional, and infectious causes). Corticosteroid responsive optic neuritis not associated with demyelinating disease should also be ruled out, including sarcoidosis, systemic lupus erythematosus, or other systemic autoimmune disease. Hereditary causes such as Leber’s hereditary optic neuropathy are also part of the differential diagnosis.
There are no current diagnostic biomarkers or imaging features typical of CRION. ANA, B12, folate, thyroid function tests, anti-aquaporin 4 antibodies (NMO-IgG), and GFAP can facilitate ruling out of other diseases. Most patients are seronegative for NMO-IgG and GFAP, biomarkers for neuromyelitis optica. ANA, indicative of autoimmune optic neuropathy, is also generally negative. CSF can also be evaluated for oligoclonal bands typical of multiple sclerosis, which will not be present in CRION. Chest X-ray or CT should be ordered if granulomatous optic neuropathy caused by sarcoidosis is suspected.
MRI imaging can capture optic nerve inflammation, but this finding is not present in all patients, Diffusion tensor imaging has been shown to detect widespread white matter abnormalities in CRION patients with normal MRI findings 
Five diagnostic criteria have been proposed:
- History of optic neuritis with one relapse
- Objectively measured visual loss
- NMO-IgG seronegative
- Contrast enhancement on imaging of acutely inflamed optic nerves
- Response to immunosuppressive treatment and relapse on withdrawal or dose reduction
Treatment consists of three phases:
- 1. Acute phase: IV steroids (methylprednisolone 1 mg/kg) for 3–5 days or plasmapheresis are given to restore visual function.
- 2. Intermediate phase: Oral steroids (typically prednisone 1 mg/kg) with taper are given to stabilize vision.
- 3. Long-term phase: To avoid adverse effects of long-term steroids and to avoid relapse of disease, physicians can transition to a steroid-sparing agent. Azathioprine, methotrexate, cyclophosphamide, mycophenolate, IVIG, plasma exchange, cyclosporine, and infliximab have been used.
Visual acuity is dramatically worse with CRION than other forms of optic neuritis. Treatment with corticosteroids induces prompt relief of pain and improved vision. At times, patients obtain complete restoration of vision, although exact success rates are unknown.
CRION was first described in 2003. The disease is rare, with only 122 cases published from 2003 to 2013. There is female predominance with 59 females (48%), 25 males (20%), and no gender designation for the rest of the 122 reported cases (32%). Age ranges from 14 to 69 years of age, and the mean age is 35.6. The disease is noted to occur worldwide and across many ethnicities, with reported cases in all continents except Africa and Australia.
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