Imaging analysis of ocular involvement in granulomatosis with polyangiitis

Introduction

Granulomatosis with polyangiitis (GPA) is an uncommon and unexplained autoimmune disease that mainly involves the arterioles, veins, and capillaries. Its pathology is characterized by inflammation of the vascular wall (1). The ocular lesions associated with this disease are uncommon and often missed in the diagnosis. Furthermore, it is prone to misdiagnosis because the clinical features of the disease are similar to those of some orbital inflammatory lesions, lymphomas, and other tumor lesions. The improvement in imaging techniques is critical to the diagnosis and disease identification of ocular lesions in GPA.

The most frequently involved tissues of GPA are the upper respiratory tract, lung, kidney, skin, eyeball, orbit, ear, joint, and lymph nodes (2). Ocular involvement ranges from 50% to 60% of GPA, and any area of the eye can be affected, with 15–20% of cases exhibiting granulomatous inflammation (3,4). If the cause of the orbital granulomatous inflammation is not identified early and treatment delayed, this may lead to serious complications of the eyes, such as loss of vision and removal of the eyeballs (5). Previous studies on orbital imaging of GPA have primarily been case reports, and a systematic description is lacking. Although, a few large-sample, clinical studies have been conducted, only clinical data have been reported, and the imaging diagnostic features and pathogenesis of the disease have not been extensively explored (6). Lacrimal gland enlargement and intraorbital pseudotumor are the common imaging manifestations of GPA (7,8), but other imaging manifestations have been identified, such as optic nerve sheath, dural matter enhancement (9,10), and extraocular myositis (11). However, these are also present in some orbital inflammatory and tumorous lesions, such as immunoglobulin G4-related ophthalmic diseases (IgG4-ROD), Graves ophthalmopathy, sarcoidosis, and lymphoma. Therefore, identifying diagnostic markers of characteristic imaging is a challenge for current research. Studies on IgG4-ROD have suggested that thickening of the suborbital nerve are characteristic imaging markers, while hypertrophy of the extraocular muscle belly is a characteristic marker of Graves ophthalmopathy. However, studies on imaging markers for GPA are rare.

Therefore, identifying the imaging manifestation of GPA involving the eyes remains a yet-to-be conducted but clinically significant object of research. Therefore, in this study, we reviewed the data of previously published imaging cases of GPA ophthalmopathy and summarized the possible ocular imaging features of GPA. Moreover, to clarify the pathogenesis and etiology of the disease, the imaging data of 10 patients clinically diagnosed with GPA involving the ocular structure were collected, the unique characteristics of the disease were identified, and the related characteristics were analyzed.

Methods

The imaging data of 10 patients clinically diagnosed with GPA involving multiple ocular structures were retrospectively analyzed. The patients with GPA were recruited from the Ophthalmology Department of Beijing Friendship Hospital, Capital Medical University. Recruitment took place from February 2016 to February 2019, and patients meeting the inclusion criteria were offered participation in the study. All the patients were required to meet the classification criteria of the American College of Rheumatology (12). Localized GPA was diagnosed according to the Chapel Hill Consensus and the European Vasculitis Society (EUVAS) recommendations (13-15) as follows: a biopsy specimen consistent with GPA (at least two of the three features of GPA, including granulomas, small-to-medium-sized vessel vasculitis, or geographic necrosis) (16) and ocular involvement of the lesion. All patients with GPA were diagnosed by experienced rheumatologists (more than 5 years of experience in rheumatology) and were subjected to imaging examination. The magnetic resonance imaging (MRI) of patients was evaluated by two experienced neuroradiologists (more than 8 years of imaging experience).

MRI scanning was performed using a 3-T scanner (GE HealthCare, Chicago, IL, USA). The eye scanning sequence and parameters were as follows: transverse T1-weighted imaging [T1WI; repetition time (TR) 600 ms; echo time (TE) 11 ms], T2-weighted imaging (T2WI; TR 3,000 ms; TE 120 ms), and coronal T2 short tau inversion recovery (STIR) (TR 3,500 ms; TE 106 ms), with an interval of 3.0–4.0 mm, an interlamellar spacing of 0.5–1.0 mm, and a field of view of 18 × 18 cm². The craniocerebral MRI scanning sequence (all transected) and parameters were as follows: sagittal T1WI (TR 2,000 ms; TE 15 ms), cross-sectional T2WI (TR 4,000 ms; TE 89 ms), cross-sectional fluid-attenuated inversion recovery (FLAIR; TR 8,000 ms; TE139 ms), and cross-sectional diffusion-weighted imaging (b=1,000 s/mm²). The contrast agent, gadolinium-diethylenetriaminepentacetate (Gd-DTPA), was administered at 0.1 mmol/kg body mass, and then T1WI scanning was performed in cross-section on the axis, sagittal, and coronal planes.

Computed tomography (CT) scanning was conducted with a Philips Brilliance 256-row CT scanner (Philips, Amsterdam, the Netherlands); the voltage of all the tubes was 120 kV, and the current was 200 and 300 mAs, respectively. The thickness of the reconstruction layer was 4 mm. The bone window [the window width and window position were 2,000 and 200 Hounsfield unit (HU), respectively] and soft tissue window (the window width and window position were 350 and 40 HU, respectively) were employed for observation.

This study was approved by the Beijing Friendship Hospital Ethics Committee (No. 2019-P2-201-01). The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Informed consent was obtained from the patients’ parents or legal guardians (V1.1/2019-09-16). All the blood samples were collected as part of routine treatment for this study.

Results

Ocular imaging manifestations in patients with GPA

Ten patients were recruited in this study. Of these, six were male and four females, with the ages being between 12 and 64 years. Both MRI of the eyes and CT scanning of accessory nasal sinuses were performed in seven patients, cranial MRI and CT scanning of accessory nasal sinuses (Figure 1) were performed in two patients, and only MRI scanning of eyes was performed in one patient.

Figure 1 A 15-year-old male patient with GPA. (A,B) Cross-sectional T2-weighted imaging showing bilateral enlargement of the lacrimal gland (arrows), which exhibited a high signal intensity compared with that of the ectocinerea. Nasal sinusitis (triangle) and bilateral middle-ear papillitis. (C,D) Computed tomography (scan of the coronal bone window showing the destruction of the nasal septum [arrow in (C)] and abnormal enhancement of basal cochlea of the patient [arrow in (D)]. GPA, granulomatosis with polyangiitis.

Lacrimal glands were involved in six patients (60%), three had bilateral symmetrical enlargement of the lacrimal glands, and three had unilateral lacrimal gland enlargement. A total of nine side lesions were present; one patient underwent surgery due to bilateral lacrimal gland enlargement, and after surgery, the pathology was determined to be necrotizing granulomatous vasculitis. All the lacrimal gland lesions occurred on the eyelid and orbit at the same time. In five patients (50%), seven lacrimal gland lesions were examined using MRI. MRI showed a slightly low signal intensity on T1WI (compared with the gray matter). T2WI showed a high signal intensity (Figure 1A). Obvious enhancement of the lacrimal gland lesions and homogeneous enhancement of the four patients were observed. Obvious uneven enhancement of three patients was also observed. The bilateral lacrimal gland lesions in three patients with CT examination showed isodensity compared with that of the extraocular muscles, and the adjacent bone showed no signs of destruction (Figure 1C).

An abnormal soft tissue shadow in the extraconal space of orbital muscles was found in nine patients (90%) (Figures 2,3). Among the 14 lesions, bilateral lesions were found in 5 patients and unilateral lesions in 4 patients. The inner lower quadrant (Figure 2A-2C) was involved in five patients (50%), and the ipsilateral lacrimal gland was involved in three patients (30%), with involvement in the outer superior quadrant. The lesions of the outer space of the muscle cone showed isosignal intensity on T1WI and slightly low isosignal intensity on T2WI, and all lesions were enhanced (Figure 4A-4C). CT examination was performed in eight patients. The lesions in the outer muscle cone were of equal density compared with that of the extraocular muscles. No signs of bony destruction were visible in the adjacent orbital wall. The local bone was coarse, with the continuity being interrupted by the thin bone in the inner wall of the orbit (Figure 1C).

Figure 2 A 46-year-old male patient with granulomatosis with polyangiitis showing abnormal soft tissue [(A) arrow] in the extraconical space of bilateral orbital muscles, mainly involving the suborbital quadrant, which was obviously strengthened after enhancement. The thickening and enhancement of endocranium could be seen [(B) curved arrow]. Abnormal contrast enhancement shadow in the bilateral pterygopalatine fossa could also be seen [(C) white arrows]. Inflammatory infiltration in the eyelid [(C) yellow arrow] was also seen.

Figure 3 A 30-year-old woman with granulomatosis with polyangiitis exhibiting left lacrimal gland enlargement (yellow arrow), inflammatory infiltration in the extraconal space adjacent to the external upper quadrant, and abnormal soft tissue in the left nasolacrimal duct involving the extraconal space adjacent to the inner and lower quadrant (white arrow).

Figure 4 A 12-year-old female patient with granulomatosis with polyangiitis. (A) Abnormal soft tissue in the extraconal space of the bilateral orbital muscles, and isosignal of T1WI observed compared with that of the ectocinerea (white arrow). (B) T2-weighted imaging had a slightly lower signal (white arrow), and middle-ear mastoiditis (yellow arrow) was found in both sides. (C) Obvious enhancement after enhancement of the mass (white arrow). (D) Magnetic resonance imaging showing thickening and enhancement of the left optic nerve sheath (yellow arrow). T1WI, T1-weighted imaging.

Inflammatory infiltration was found in nine patients with orbital fat (90%) (17 sides), and eyelid swelling was found in nine patients (90%) (18 sides; Figure 2C). Three patients (30%) showed thickening and enhancement of the optic nerve sheath (Figure 4D).

Other concomitant structural and organ abnormalities

Nasosinusitis was found in all 10 patients (100%), 4 (40%) of whom had nasal septal bone destruction (Figure 1C), and the left nasal cavity of 1 patient (10%) showed postoperative manifestations. An abnormal soft tissue shadow was found in the nasolacrimal duct and pterygopalatine fossa of 10 patients (Figures 2C,3,5). MRI showed that T1WI had an equal signal, and T2WI had an equal and high signal intensity and was enhanced. Dural thickening and enhancement was found in seven patients (70%) (Figure 2B), mainly involving the anterior skull base meninges in three patients and the bilateral cavernous sinus and middle skull base meninges in two patients (20%). Diffuse thickening and enhancement of the intracranial dura mater was found in two patients (20%), bilateral otitis media and mastoiditis in five (50%) patients (Figures 1B,4B), and abnormal enhancement of the basal cochlea in one patient (Figure 1D). Soft tissue involvement was found in the maxillofacial region in one patient (Figure 5).

Figure 5 A 28-year-old female patient with granulomatosis with polyangiitis. After left nasal cavity operation, the maxillary sinus wall was incomplete. There was inflammatory infiltration around the antrum, involving the pterygopalatine fossa, retromaxillary fat space, and subcutaneous maxillofacial region (white arrow).

Abnormal changes were found in the lungs of five patients (50%), including patch, nodule, and stripe shadow.

Discussion

GPA may involve any part of the eye and can include conjunctivitis, helcoma, leucitis, retinal vasculitis, and optic neuropathy (17). In the past, most of the imaging literature related to GPA has been in the form of case reports (Table 1). The imaging manifestations of GPA orbital lesions include enlarged lacrimal glands, granulomatous inflammation, extraocular myositis, and optic perineuritis. However, these studies only described the imaging features, and the mechanisms of the related imaging features were not analyzed (6,18-25). In one retrospective study of 226 patients in ophthalmology, 74 were examined with CT or MRI. The patients were divided into three groups: a lacrimal gland enlargement group, orbital tumor group, and extraocular myositis group. However, this study was an epidemiological study of the orbit and focused on the description of the clinical manifestations of the eye, but the imaging features of the orbit were not described or analyzed (11).

A characteristic imaging feature of the group of patients in this study was that the intraorbital granuloma inflammation was mainly located in the extraconal space. This may have two principal explanations: one was the invasion of granuloma adjacent to paranasal sinus or nasal cavity, and the other was that the GPA involved the lacrimal glands, resulting in bilateral or unilateral enlargement of these glands (26), with formation of inflammatory granuloma in the outer space of the extraorbital superior quadrant muscle simultaneously with that of the lacrimal glands. These two phenomena could be concurrent, but the former likely exerted the greatest effect. In our study, one patient exhibited an unusual course of disease spread. The nasolacrimal duct and adjacent medial inferior quadrant muscle cones of the patient were involved, and the lacrimal gland was enlarged with inflammatory infiltration of the outer space of the upper quadrant muscle cone. There are three main histological changes in GPA-associated granuloma: parenchymal tissue injury, vasculitis, and granulomatous inflammation. Inflammation tends to spread from a certain areas, such as the orbit, which can stimulate the production of tumor-like changes. This often results in the formation of inflammatory pseudotumor-like masses in areas with abundant blood flow.

Another characteristic imaging manifestation, which was evident in all patients in this study, was inflammatory infiltration of the pterygopalatine fossa, with the pterygopalatine fossa lesions of the transcranial basal foramen involving the adjacent sinus cavernosus, orbital apex, masticatory muscle space, and other structures being visible. In other studies (27,28), the orbital pseudotumor was reported to combine with adjacent disease within the paranasal sinuses or to extend posteriorly to the cavernous sinus. Moreover, it has been speculated that the inflammation of paranasal sinuses could pass through the pterygopalatine fossa due to numerous and interconnected channels in the skull base. The skull is involved through the structures of the foramen, canal, and suborbital fissure connected to the pterygopalatine fossa, leading to the thickening and enhancement of endocranium.

GPA also involves the optic nerve sheath, which is characterized by the thickening and strengthening of the optic nerve sheath due to the involvement of inflammatory cells in the optic nerve sheath (23). In addition to the ocular and endocranium changes, patients with GPA might often have middle-ear mastoiditis. Abnormal enhancement of the underlying cochlea were observed in one patient in this study, which is consistent with other reported cases (29,30).

In clinical work, GPA, IgG4-related diseases, and thyroid-associated ophthalmopathy involve multiple structures of the eye. These three diseases are common autoimmune diseases. Therefore, recognizing the similarities and differences of their imaging manifestations in clinic is critical.

Many types of diseases can give rise to orbital pseudotumor. The common clinical diseases include GPA, thyroid-associated ophthalmopathy, and IgG4-related diseases, all of which have been studied in recent years (31). Although all three of these diseases could result in the formation of intraorbital pseudotumor, obvious differences can be discerned between them. GPA formation of the orbital inflammatory pseudotumor is mainly concentrated in the external space of the muscle cone, especially in the inner inferior quadrant. The characteristic feature of IgG4 involving ocular herniation is the involvement of the trigeminal nerve branches, resulting in its thickening. The perineural growth of the disease might be one of the characteristic imaging signs of the disease (31). The prominent feature of thyroid-associated ophthalmopathy is the thickening and protruding of extraocular muscles. The trigeminal nerve branches were not involved in the GPA observed in this study, and the extraocular muscles were not thickened. To our knowledge, no evidence of trigeminal nerve branching or extraocular muscle involvement in patients with GPA has been reported thus far.

In our study, the signal intensity of T2WI in GPA lacrimal gland lesions was high and the T2WI signal of the IgG4-involved lacrimal glands was low, which might be related to the pathological changes in these glands, including fibrosis (32). Meanwhile, the lacrimal glands were enlarged in patients with thyroid-associated ophthalmopathy. GPA involves the thickening and strengthening of the optic nerve sheath. However, in patients with IgG4 and thyroid-associated ophthalmopathy, the optic nerve sheath was involved, and among the patients with GPA, IgG4, or thyroid-associated ophthalmopathy, the eyelid soft tissue and orbital fat body were involved. Therefore, the involvement of these structures is of little significance for differentiating between these three diseases (33).

In addition to ocular changes, the patients with GPA also exhibited dural thickening and strengthening, middle-ear mastoiditis, and abnormal enhancement of the underlying cochlea, which have not been reported in the patients with IgG4-related diseases or thyroid-associated ophthalmopathy.

The MRI manifestations vary across different inflammatory orbital diseases (33). The most prominent feature of thyroid-associated ophthalmopathy is the thickening and protruding of extraocular muscles (34). Characteristic ophthalmologic findings in with patients with IgG4-ROD include ocular herniation with involvement of trigeminal nerve branches and nerve thickening (35). In patients with GPA, orbital inflammatory pseudotumor in the external space of the muscle cone is common, especially in the inner inferior quadrant. Meanwhile, sarcoidosis is characterized by diffuse inflammation of the eye, which can involve the eyeball, the orbit, and the extraocular muscles, and the main manifestations are inflammatory pseudotumor in the orbit and peripheral optic neuropathy. One differential diagnosis to consider in clinical work is ocular lymphoma, which occurs mainly in the conjunctiva and can also involve multiple structures, such as the lacrimal gland, eyelid, lacrimal sac, and lacrimal port bilaterally. However, the signal intensity of ocular lymphoma is more homogeneous, the enhancement is mild and moderate (36), and no meningeal thickening or enhancement or middle-ear mastoiditis occur.

Limitations

Our study was a case series, employed a retrospective design, and was limited to a single center. Stringent inclusion criteria also limited our sample size to 10 cases which might have underpowered some aspects of the study.

Conclusions

The characteristic imaging feature of GPA is inflammatory granuloma in the extraconal space accompanied by infiltration of the pterygopalatine fossa. Thyroid-associated ophthalmopathy is characterized by the thickening and protruding of extraocular muscles, and IgG4-ROD is characterized by ocular herniation with involvement of the trigeminal nerve branches. Meanwhile, the enhancement of lymphoma is mild and moderate.

Acknowledgments

Funding: This work was supported by the National Natural Science Foundation of China (No. 82272072) and the Capital Health Development Research Special Project (No. 2022-2-20211).

Footnote

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-239/coif). All authors report receiving funding from the National Natural Science Foundation of China (No. 82272072) and the Capital Health Development Research Special Project (No. 2022-2-20211). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the Beijing Friendship Hospital Ethics Committee (No. 2019-P2-201-01). The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Informed consent was obtained from the patients’ parents or legal guardians (V1.1/2019-09-16).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Pokharel S, Singh S, Shaukat MS. An Unusual Presentation of Granulomatosis with Polyangiitis (GPA). Am J Case Rep 2018;19:1071-3. [Crossref] [PubMed]
2. Hellmich B, Sanchez-Alamo B, Schirmer JH, Berti A, Blockmans D, Cid MC, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis 2024;83:30-47. [Crossref] [PubMed]
3. Takamasu E, Yokogawa N, Shimada K. Optic perineuritis in eosinophilic granulomatosis with polyangiitis. Rheumatology (Oxford) 2024;63:e195. [Crossref] [PubMed]
4. Rothschild PR, Pagnoux C, Seror R, Brézin AP, Delair E, Guillevin L. Ophthalmologic manifestations of systemic necrotizing vasculitides at diagnosis: a retrospective study of 1286 patients and review of the literature. Semin Arthritis Rheum 2013;42:507-14. [Crossref] [PubMed]
5. Pakalniskis MG, Berg AD, Policeni BA, Gentry LR, Sato Y, Moritani T, Smoker WR. The Many Faces of Granulomatosis With Polyangiitis: A Review of the Head and Neck Imaging Manifestations. AJR Am J Roentgenol 2015;205:W619-29. [Crossref] [PubMed]
6. Tan LT, Davagnanam I, Isa H, Taylor SR, Rose GE, Verity DH, Pusey CD, Lightman S. Clinical and imaging features predictive of orbital granulomatosis with polyangiitis and the risk of systemic involvement. Ophthalmology 2014;121:1304-9. [Crossref] [PubMed]
7. Kiseleva TN, Grusha IaO, Polunina AA, Semenkova EN, Abdurakhmanov GA, Nikol'skaia GM. Involvement of lacrimal organs in Wegener's granulomatosis. Vestn Oftalmol 2009;125:33-6. [PubMed]
8. Holle JU, Voigt C, Both M, Holl-Ulrich K, Nölle B, Laudien M, Moosig F, Gross WL. Orbital masses in granulomatosis with polyangiitis are associated with a refractory course and a high burden of local damage. Rheumatology (Oxford) 2013;52:875-82. [Crossref] [PubMed]
9. Purvin V, Kawasaki A. Optic perineuritis secondary to Wegener's granulomatosis. Clin Exp Ophthalmol 2009;37:712-7. [Crossref] [PubMed]
10. Yajima R, Toyoshima Y, Wada Y, Takahashi T, Arakawa H, Ito G, Kobayashi D, Yamada M, Kawachi I, Narita I, Takahashi H, Nishizawa M. A Fulminant Case of Granulomatosis with Polyangiitis with Meningeal and Parenchymal Involvement. Case Rep Neurol 2015;7:101-4. [Crossref] [PubMed]
11. Ismailova DS, Abramova JV, Novikov PI, Grusha YO. Clinical features of different orbital manifestations of granulomatosis with polyangiitis. Graefes Arch Clin Exp Ophthalmol 2018;256:1751-6. [Crossref] [PubMed]
12. Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, Calabrese LH, Fries JF, Lie JT, Lightfoot RW Jr, Masi AT, McShane DJ, Mills JA, Stevens MB, Wallace SL, Zvaifler NJ. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum 1990;33:1101-7. [Crossref] [PubMed]
13. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994;37:187-92. [Crossref] [PubMed]
14. Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, de Groot K, Gross W, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 2009;68:310-7. [Crossref] [PubMed]
15. Hellmich B, Flossmann O, Gross WL, Bacon P, Cohen-Tervaert JW, Guillevin L, Jayne D, Mahr A, Merkel PA, Raspe H, Scott DG, Witter J, Yazici H, Luqmani RA. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis 2007;66:605-17. [Crossref] [PubMed]
16. Devaney KO, Travis WD, Hoffman G, Leavitt R, Lebovics R, Fauci AS. Interpretation of head and neck biopsies in Wegener's granulomatosis. A pathologic study of 126 biopsies in 70 patients. Am J Surg Pathol 1990;14:555-64. [Crossref] [PubMed]
17. Wojciechowska J, Krajewski W, Krajewski P, Kręcicki T. Granulomatosis With Polyangiitis in Otolaryngologist Practice: A Review of Current Knowledge. Clin Exp Otorhinolaryngol 2016;9:8-13. [Crossref] [PubMed]
18. Drobysheva A, Fuller J, Pfeifer CM, Rakheja D. Orbital Granulomatosis With Polyangiitis Mimicking IgG4-Related Disease in a 12-Year-Old Male. Int J Surg Pathol 2018;26:453-8. [Crossref] [PubMed]
19. Fechner FP, Faquin WC, Pilch BZ. Wegener's granulomatosis of the orbit: a clinicopathological study of 15 patients. Laryngoscope 2002;112:1945-50. [Crossref] [PubMed]
20. Martínez-Gutiérrez JD, Mencía-Gutiérrez E, Gutiérrez-Díaz E, Rodríguez-Peralto JL. Bilateral idiopathic orbital inflammation 3 years before systemic Wegener's granulomatosis in a 7-year-old girl. Clin Ophthalmol 2008;2:941-4. [Crossref] [PubMed]
21. Bowers B, Gupta D, Patel H, Mirza N. Exophthalmos as a presenting manifestation of limited Wegener's granulomatosis in a patient with prior graves' disease. Clin Med Case Rep 2009;2:35-7. [Crossref] [PubMed]
22. Yang B, Yin Z, Chen S, Yuan F, Zhao W, Yang Y. Imaging diagnosis of orbital Wegener granulomatosis: A rare case report. Medicine (Baltimore) 2017;96:e6904. [Crossref] [PubMed]
23. Kimura Y, Asako K, Kikuchi H, Kono H. Refractory optic perineuritis due to granulomatosis with polyangiitis successfully treated with methotrexate and mycophenolate mofetil combination therapy. Eur J Rheumatol 2017;4:70-2. [Crossref] [PubMed]
24. Kenny GM, Holl-Ulrich K, Fulcher T, McElnea E, Kavanagh E, Moriarty H, Mulligan N, Molloy ES, McCarthy GM. Successful reconstruction of an ocular defect resulting from granulomatosis with polyangiitis, following treatment with rituximab. Am J Ophthalmol Case Rep 2018;10:240-3. [Crossref] [PubMed]
25. Takazawa T, Ikeda K, Nagaoka T, Hirayama T, Yamamoto T, Yanagihashi M, Tochikubo T, Iwasaki Y. Wegener granulomatosis-associated optic perineuritis. Orbit 2014;33:13-6. [Crossref] [PubMed]
26. Santiago YM, Fay A. Wegener's granulomatosis of the orbit: a review of clinical features and updates in diagnosis and treatment. Semin Ophthalmol 2011;26:349-55. [Crossref] [PubMed]
27. Holle JU, Gross WL. Neurological involvement in Wegener's granulomatosis. Curr Opin Rheumatol 2011;23:7-11. [Crossref] [PubMed]
28. Cleary JO, Sivarasan N, Burd C, Connor SEJ. Head and neck manifestations of granulomatosis with polyangiitis. Br J Radiol 2021;94:20200914. [Crossref] [PubMed]
29. Al-Hakami H, Al-Arfaj AS, Al-Sohaibani M, Khalil NA. An eosinophilic variant granulomatosis with polyangiitis involving the dura, bilateral orbits, and mastoids. Saudi Med J 2016;37:690-3. [Crossref] [PubMed]
30. Hermann J, Reittner P, Scarpatetti M, Graninger W. Successful treatment of meningeal involvement in Wegener's granulomatosis with infliximab. Ann Rheum Dis 2006;65:691-2. [Crossref] [PubMed]
31. Rosenbaum JT, Choi D, Wilson DJ, Grossniklaus HE, Harrington CA, Sibley CH, et al. Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling. Exp Mol Pathol 2015;99:271-8. [Crossref] [PubMed]
32. Tiegs-Heiden CA, Eckel LJ, Hunt CH, Diehn FE, Schwartz KM, Kallmes DF, Salomão DR, Witzig TE, Garrity JA. Immunoglobulin G4-related disease of the orbit: imaging features in 27 patients. AJNR Am J Neuroradiol 2014;35:1393-7. [Crossref] [PubMed]
33. Li J, Zhang Y, Zhou H, Wang L, Wang Z, Li H. Magnetic resonance imaging indicator of the causes of optic neuropathy in IgG4-related ophthalmic disease. BMC Med Imaging 2019;19:49. [Crossref] [PubMed]
34. Szelog J, Swanson H, Sniegowski MC, Lyon DB. Thyroid Eye Disease. Mo Med 2022;119:343-50. [PubMed]
35. Soussan JB, Deschamps R, Sadik JC, Savatovsky J, Deschamps L, Puttermann M, Zmuda M, Heran F, Galatoire O, Picard H, Lecler A. Infraorbital nerve involvement on magnetic resonance imaging in European patients with IgG4-related ophthalmic disease: a specific sign. Eur Radiol 2017;27:1335-43. [Crossref] [PubMed]
36. Olsen TG, Heegaard S. Orbital lymphoma. Surv Ophthalmol 2019;64:45-66. [Crossref] [PubMed]