| Chronic relapsing inflammatory optic neuropathy | |
| Synonyms: | Chronic relapsing inflammatory optic neuritis |
| Field: | Ophthalmology, Neurology, Neuro-ophthalmology |
| Diagnosis: | Consensus Diagnostic Criteria |
| Differential: | Optic neuritis subgroups |
| Treatment: | Corticosteroids |
Chronic relapsing inflammatory optic neuropathy (CRION) is a form of recurrent optic neuritis that is steroid responsive and dependent.[1] Patients typically present with pain associated with visual loss.[1] CRION is a clinical diagnosis of exclusion, and other demyelinating, autoimmune, and systemic causes should be ruled out.[2] An accurate antibody test which became available commercially in 2017 has allowed most patients previously diagnosed with CRION to be re-identified as having MOG antibody disease, which is not a diagnosis of exclusion. Early recognition is crucial given risks for severe visual loss and because it is treatable with immunosuppressive treatment such as steroids[2] or B-cell depleting therapy.[3] Relapse that occurs after reducing or stopping steroids is a characteristic feature.[2]
Pain, visual loss, relapse, and steroid response are typical of CRION.[1] [2] Ocular pain is typical, although there are some cases with no reported pain.[2] Bilateral severe visual loss (simultaneous or sequential) usually occurs, but there are reports of unilateral visual loss.[2] Patients can have an associated relative afferent pupillary defect.[4] CRION is associated with at least one relapse, and up to 18 relapses have been reported in an individual.[5] Intervals between episodes can range from days to over a decade.[1] Symptoms will improve with corticosteroids, and recurrence characteristically occurs after reducing or stopping steroids.[2]
In 2013, the etiology was unknown.[1] Given that CRION is responsive to immunosuppressive treatment, it was presumed to be immune-mediated,[2] but this was uncertain as at the time there were no known associated autoimmune antibodies.[2] [6]
In 2015, some research pointed to CRION belonging to the MOG antibody-associated encephalomyelitis spectrum.[7]
As of 2019, the correlation between CRION and MOG antibody-associated encephalomyelitis is so high that now CRION is considered the most common phenotype related to myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).[8]
As of 2021, some reports point out a second kind of CRION due to anti-phospholipid antibodies.[9]
In 2018, of 12 patients in a study who fulfilled the then-current diagnostic criteria for CRION, eleven (92%) were positive for MOG-IgG, and the last patient was borderline. Diagnosis requires exclusion of other neurological, ophthalmological, and systemic conditions.[2] Any cause of optic neuropathy should be ruled out, including demyelinating (MOG antibody disease, multiple sclerosis, and neuromyelitis optica) and systemic disease (diabetic, toxic, nutritional, and infectious causes).[2] Corticosteroid responsive optic neuritis not associated with demyelinating disease should also be ruled out, including sarcoidosis, systemic lupus erythematosus, or other systemic autoimmune disease.[10] Hereditary causes such as Leber's hereditary optic neuropathy are also part of the differential diagnosis.[11]
In 2014, there were no diagnostic biomarkers or imaging features typical of CRION.[2] Antinuclear antibodies (ANA), B12, folate, thyroid function tests, anti-aquaporin-4 antibodies (NMO-IgG), and glial fibrillary acidic protein (GFAP) can facilitate ruling out of other diseases.[2] Most patients are seronegative for NMO-IgG and GFAP, biomarkers for neuromyelitis optica.[2] ANA, indicative of autoimmune optic neuropathy, is also generally negative.[2] CSF can also be evaluated for oligoclonal bands typical of multiple sclerosis, which will not be present in CRION.[1] A chest X-ray or CT scan should be ordered if granulomatous optic neuropathy caused by sarcoidosis is suspected.[2]
Magnetic resonance imaging can capture optic nerve inflammation, but this finding is not present in all patients,[1] [2] [12] Diffusion tensor imaging has been shown to detect widespread white matter abnormalities in CRION patients with normal MRI findings.[13]
Five diagnostic criteria had been proposed in 2014:[2]
CRION has been included as a subtype in a 2022 international consensus classification of optic neuritis.[14]
Treatment consists of three phases of immunotherapy:
Visual acuity is dramatically worse with CRION than other forms of optic neuritis.[2] Treatment with corticosteroids induces prompt relief of pain and improved vision.[1] At times, patients obtain complete restoration of vision, although exact success rates are unknown.[1]
Recurrence is essentially inevitable in patients without treatment, and patients ultimately will require lifelong immunosuppression to prevent relapse.[2] [15]
CRION was first described in 2003.[1] The disease is rare, with only 122 cases published from 2003 to 2013.[2] There is female predominance with 59 females (48%), 25 males (20%), and no gender designation for the rest of the 122 reported cases (32%).[2] Age ranges from 14 to 69 years of age, and the mean age is 35.6.[2] The disease is noted to occur worldwide and across many ethnicities, with reported cases in all continents except Africa and Australia.[2]