OPN is an uncommon orbit inflammatory disease(7) and most prior literature has come in the form of case reports(8). A cohort of 14 patients with idiopathic OPN was reported in 2001(1). This study identified demographic and clinical characteristics of patients with OPN, which included mostly middle-aged females with unilateral presentation, +/- eye pain, mild visual impairment, and optic disc edema. Visual field abnormalities included arcuate defects, paracentral scotomas, central scotomas, and peripheral island defects(3). The clinical manifestations and characteristics of the patients in our study are quite different. This may be due to the differing OPN etiologies, as many of the patients in this small cohort had idiopathic OPN not associated with another specific condition.
It has been previously established that OPN is an orbital inflammatory disease that is different from IDON(9). Our study illustrates some of the differences between OPN and IDON, which include clinical characteristics, imaging features, and prognosis. We found that OPN are more often with CTD and IDON are more often associated with idiopathic inflammation, such as MS and NMO. Orbital MRI showed low or equal signal on T1WI and slightly low signal on T2WI. In OPN, contrast-enhanced scans showed that most of the optic nerve sheath presented a strip-like or nodular uniform enhancement with unclear boundaries. Optic nerve and sheath enhancement were present in IDON. Soft tissue inflammation in the orbit has also been found in OPN, yet inflammation of the orbit is rare in IDON. Unlike OPN, optic nerve sheath enhancement in IDON is almost always accompanied by more prominent optic nerve parenchyma enhancement.
Known CTD etiologies of OPN include sarcoidosis (10, 11), GAP (12, 13), giant cell arteritis (14, 15), Crohn’s disease (16), IgG-4 (17), Behcet's disease (9), and SLE (2). Infectious etiologies of OPN have been associated with acute retinal necrosis (18), syphilis (19, 20), herpes zoster (21), tuberculosis (22, 23), and Mycoplasma pneumoniae (24). In our study we found the primary causes of OPN were Graves’ diseases (12), IgG-4(10), GPA (4), SLE (2), sarcoidosis (1), rheumatoid disease (1), scleroderma (1), Behcet's disease (1), gout (1), tuberculosis (5), sparganosis (1), ocular Toxoplasmosis (1), bacterial meningitis (1), fungal meningitis (1), and Cytomegalovirus (1). Unlike published reports, we did not find and OPN associated with syphilis and giant cell arteritis, which may be due to our small sample size and single center study. The finding of OPN associated with Graves’ disease is unique to our study. We found that orbital fat inflammation was always associated with inflammation of the optic nerve sheath, suggesting that inflammatory invasion of orbital fat may be the primary pathogenic mechanism of OPN in patients with Graves’ disease.
In GPA, formation of an orbital inflammatory pseudotumor was mainly concentrated in the external space of the muscle cone, especially in the inner inferior quadrant (25). OPN patients with IgG-4 often had ocular herniation involving the trigeminal nerve branches, which resulted in its thickening, suggesting perineural growth may be a characteristic imaging finding of OPN (26). The most prominent feature of thyroid-associated ophthalmopathy is the thickening and protruding of extraocular muscles (27). The trigeminal nerve branches were not involved in the OPN of the GPA patients in this study and the extraocular muscles were not thickened. We were unable to find any prior reports of trigeminal nerve branching and extraocular muscle involvement in patients with GPA, Graves’, and sarcoidosis.
CTDs are a group of diseases that affect bones, joints, and surrounding soft tissue, such as muscles, bursa, tendons, fascia, and nerves (28). Chronic inflammation, mediated by T and B lymphocytes, eosinophils, and macrophages, activates fibroblasts to induce collagen deposition, and ultimately leads to tissue proliferation and dural thickening (29). The optic nerve is a continuation of the central nervous system with a dura, arachnoid, and pia mater. Therefore, the optic nerve sheath is also susceptible rheumatic CTDs. Orbital MRI showed low or equal signal on T1WI and slightly low signal on T2WI. Contrast-enhanced scanning showed that most of the optic nerve sheath had strip-like or nodular uniform enhancement with unclear boundaries. Most cases of soft tissue inflammation in the orbit have been found in OPN, differing it from the imaging findings in IDON. We speculate that OPN may be caused by orbital soft tissue inflammation and that the damage of the optic nerve sheath could be from antigen/antibody-mediated destruction associated with rheumatic disease.
Anti-myelin oligodendrocyte glycoprotein (MOG) autoantibodies have been identified in both children and adults with demyelination and are strongly associated with bilateral or recurrent optic neuritis (30). However, anti-MOG antibodies have not been found in patients with OPN (31) and we did not detect these antibodies in our study.
Limitations of this study include its retrospective design and recruitment of patients form only one medical center. Only 44 cases were included in this study due to inability to follow-up with some patients who initially met the inclusion criteria. Multi-center, large sample, case-control prospective studies are needed to further understand OPN pathogenesis and its relationship with other diseases.