Background
IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder characterized by IgG4-positive lymphoplasmacytic infiltrative lesions and elevated serum IgG4 levels [
1,
2]. Target organs that are most commonly affected by IgG4-RD are the orbits, salivary and lacrimal glands, lungs, kidneys, prostate, aorta and retroperitoneum, lymph nodes, biliary tree and as visceral inflammatory pseudo tumours. In the USA, 23% of all of IgG4-RD cases, the disease manifests in the eye or orbit. Furthermore, lacrimal gland swelling was found in 4 to 34% IgG4-RD cases in Japanese reviews.
Eyes are often the first most frequent site associated with IgG4-RD [
3]. A number of orbital inflammatory cases, formerly considered as other idiopathic lesions, are now regarded as IgG4-related orbital diseases (IgG4-ROD) [
4]. Radiology image is important to distinguish IgG4-ROD from other orbital diseases. IgG4-ROD usually presents as dacryoadenitis, myositis, or inflammation of infraorbital fat. In addition, some researches have indicated that the presence of infraorbital nerve enlargement (IONE) is considered as a key sign of IgG4-ROD on an MRI [
5].
Optic neuropathy may be involved in IgG4-ROD, and it can lead to severe injuries. However, this type of disease is more likely misdiagnosed as other orbital inflammatory diseases, such as optic neuritis, Graves’ disease, inflammatory pseudotumor, lymphoma, sarcoidosis and so on [
6]. IgG4-ROD is quite different from these diseases with reference to treatment and prognosis [
3]. Therefore, its early diagnosis is very important. Over the recent years, much knowledge has been gained about the clinical manifestations of IgG4-ROD [
7]; yet, most of studies were small case series, and only few explored the imaging manifestations of IgG4-ROD related optic neuropathy. Clinical data have suggested that decreased visual acuity and defective visual field are the first symptoms to appear. Nevertheless, most of the existing studies have focused on dacryoadenitis, myositis and branch of trigeminal neuropathy [
8,
9]. In addition, there is insufficient information on radiological features of optic neuropathy with IgG4-ROD, and causes of optic neuropathy in IgG4-ROD.
Hence, the purpose of this study was to investigate the radiological features of optic neuropathy from IgG4-ROD in Chinese patients. Furthermore, we suggest a radiological diagnostic criterion for optic neuropathy cases diagnosed as IgG4-ROD.
Discussion
IgG4-RD is characterized by elevated serum IgG4 levels and IgG4-positive lymphoplasmacytic infiltrative lesions [
1,
2] and it involves multiple organs, including ocular structures [
13,
14]. Previous studies, investigating IgG4-related ophthalmic diseases, have been mainly focused on examining ocular adnexa, dacryoadenitis, myositis and branch of trigeminal neuropathy lesions. In contrast, optic neuropathy is a frequent cause of vision loss encountered by ophthalmologist, which often leads to more severe injuries compered to ocular adnexa lesions. Thus, real-team imaging methods are an important tool for identifying the pathogenesis of optic neuropathy.
In the current study, we used MRI to determine the causes of optic neuropathy development, such as hypophysis, extraocular muscle enlargement, hypertrophic cranial pachymeningitis, compressed by pseudotumor masses and optic nerve sheath inflammation. Currently, the most commonly used imaging modalities for IgG4-ROD are computed tomography (CT) and MRI [
15‐
17]. In the current study, all the patients underwent MRI, since CT imaging of optic nerve and optic nerve sheath were not clear enough. Previous data have indicated that the most common structural lesions include lacrimal gland (62–88% of cases), orbital fat (29–40%), EOM (19–25%), and trigeminal nerve (10–39%) [
18,
19]. Other structures may involve eyelid, conjunctiva [
20], optic nerve [
21,
22] and mass compression. Song et al have found that IgG4-ROD mass lesions possess homogenous internal architecture, well-defined margins, contrast enhancement, and no destruction of orbit bone [
23]. In this study, compression was the main cause of optic nerve damage, especially the mass compression, and most EOMs belonged to the pseudotumor mass compression, because the hypertrophy of the EOMs is a characteristic of pseudotumor mass. Previous data have suggested that IgG4-RD has a particular tropism for cranial nerves [
24‐
26]. In addition, it has been reported that IONE can oppress the optic nerve at the orbital apex [
27]. However, in this study, we observed no IONE oppression related cases, while most oppressions were caused by pseudo tumor. In the current study, all the cases showed bilateral involvement, while 80.77% (21/26 cases) showed extraophthalmic involvement. Moreover, a Korean study group found that bilateral involvement, longer duration of symptom and higher IgG4 levels are all significant risk factors for extraophthalmic involvement in patients with IgG4-ROD [
28]. IgG4-ROD with optic neuropathy involvement was more likely combined with extraophthalmic disorder. Accordingly, optic nerve involvement might be considered as another risk factor for extraophthalmic involvement.
IONE is the main sign for differentiating optic nerve sheath inflammation of IgG4-ROD from other orbital diseases. The orbital region is the first most frequent site of the head and neck region associated with the suffering from IgG4-RD. [
3,
4] The main pathogenesis of optic neuropathy is compression; however, optic nerve sheath inflammation is also commonly observed. In addition, optic nerve sheath inflammation is often involved in unidiopathic orbital inflammation diseases [
6]. IgG4-ROD diagnoses may be useful for the adequate management and appropriate care of their patients. In the current study, matched patients with non-IgG4 ROD were compared with IgG-4 ROD patients, IONE was found to be a specific sign of IgG4-ROD. A previous research has identified an association between the enlargement of infraorbital branch of the trigeminal nerve and the IgG4-ROD [
15,
19,
29]. In previously mentioned study on IgG4-ROD that included European and Japanese study group, IONE was considered as the specific radiological feature [
5,
30]. In addition, according to radiological reviews on IgG4-ROD, trigeminal nerve enlargement occured in 24% (4/17 cases) [
9], 29% (20/68 cases) [
29], 39% (25/65 cases) [
19], and 50% (8/16 cases) of cases [
15]. In addition, one study (
n = 14) found that 50% of patients with IONE had IgG4-ROD [
26].
Our study has few limitations. This is a study with retrospective design that was conducted only in two centers, thus non-controlled investigation and treatment protocol were considered as limitations. In addition, only 26 cases were included in this study, which means that future studies should include bigger sample size.
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