Orbital Inflammatory and Infectious Conditions by Compartment

Optic Nerve and Sheath

Optic Neuritis:

Optic neuritis is inflammation of the optic nerve, most commonly due to multiple sclerosis. Other demyelinating causes include neuromyelitis optica and MOG-associated disease, while non-demyelinating causes include infections and Behçet’s disease.

Imaging: MRI shows a swollen optic nerve with increased T2 signal and contrast enhancement, best seen on coronal images.

Fig 1: Optic neuritis. T2W FS coronal image shows an increased signal in the intraorbital segment of the left optic nerve (arrow).

Fig 2: T1W post-contrast coronal image shows increased contrast enhancement in the left optic nerve (arrow) of the same patient as Fig 1.

Fig 3: Ischemic optic neuropathy of the left optic nerve. DWI image shows increased signal of the left optic nerve(arrow), corresponding ADC map showed that this signal was due to true diffusion restriction.

Optic Perineuritis:

Inflammation of the optic nerve sheath, presenting similarly to optic neuritis but with different etiologies, including idiopathic, autoimmune, and infectious causes.

Imaging: MRI shows optic nerve sheath enhancement, with the tram-track sign (axial/sagittal) and donut sign (coronal).

Fig 4: Bilateral optic perineuritis. Arrows indicate increased enhancement of bilateral optic nerve sheaths following contrast administration.

Fig 5: Meningioma of the right optic nerve sheath. Arrow indicates thick, enhancing mass surrounding the right optic nerve. Differentiation from optic perineuritis on imaging may be hard in some exaggerated perineuritis cases. Clinical presentation and course can help in such instances.

Ocular Globe

Uveitis & Scleritis:

Uveitis is inflammation/infection of the uveal tract. Anterior uveitis is mostly idiopathic or inflammatory, while posterior uveitis is often infectious. Associated systemic diseases include HLA-B27 spondyloarthropathies, rheumatoid arthritis, Behçet’s disease, Vogt-Koyanagi-Harada disease, and sarcoidosis.

Scleritis is inflammation/infection of the sclera, usually idiopathic but also linked to systemic inflammatory diseases.

Uveitis and scleritis are generally diagnosed with the history and clinical examination. 

Imaging: MRI shows uveal/scleral thickening and enhancement. Uveitis may cause vitreous signal changes, while scleritis can show periscleral cellulitis. Nodular forms may mimic neoplasms, but pain and the absence of diffusion restriction favor inflammation.

Fig 6: A patient with Vogt-Koyanagi-Harada disease. Arrows show uveal thickening and subtle retrobulbar fat stranding.

Fig 7: After contrast administration, there is enhancement of posterior uvea on both sides, indicating uveitis.

Endophthalmitis-Panophthalmitis:

Endophthalmitis is infection of the ocular globe that does not extend beyond sclera. It's called panophthalmitis if it extends beyond sclera. The source of infection may be endogenous or exogenous. The most common exogenous cause is infection after cataract surgery. Endogenous infection is usually by the hematogenous spread of microorganisms. Prompt diagnosis is essential to prevent vision loss. 

Imaging: Ultrasound shows intraocular debris, septae, retinal/choroidal detachment, and thickening. CT may reveal proptosis, fat stranding, and choroidal/scleral enhancement. MRI shows intraocular diffusion restriction, virtually diagnostic for endophthalmitis. Increased FLAIR/T1 vitreous signal suggests proteinaceous content.

Fig 8: Panophthalmitis of the left ocular globe. Precontrast T1W image shows increased signal in ocular globe, suggesting proteinaceous content. There is also hypointensity surrounding the eye, especially in the preseptal region.

Fig 9: After contrast administration, there is diffuse enhancement of the choroid ,sclera, preseptal region and intraconal fatty tissues suggesting inflammation. Also note enhancement around left optic nerve, suggesting perineuritis.

Fig 10: ADC map shows marked diffusion restriction in the ocular globe, consistent with panopthtalmitis.

Lacrimal Gland:

The infection or inflammation of lacrimal gland is called dacryoadenitis. Main non-infectious etiologies are sarcoidosis, Sjögren syndrome, IgG4-RD and IOI. Symptoms include pain, redness and swelling around lacrimal glands. 

Imaging: Unilateral or bilateral gland enlargement with increased T2 signal and enhancement. Diffusion restriction suggests abscess formation. There may be signs of surrounding cellulitis. Gland atrophy is seen in chronic inflammation. The most important mimicker for lacrimal gland inflammation is lymphoma. Lymphoma tends to have very low ADC values and in the context of chronic inflammation and glandular atrophy as seen in Sjögren disease, acute enlargement of the gland is again suspicious of lymphoma. Other benign or malignant tumors of lacrimal glands should also be considered, especially in unilateral cases.  Signs of surrounding cellulitis are not seen in tumors.

Fig 11: T1W post-contrast coronal image shows bilateral diffusely enhancing lacrimal glands that increased in size (arrows) in a patient with IgG4 related disease. The inflammatory changes also involved the superior rectus muscle on the right side.

Fig 12: Post-treatment images of the patient in Fig 11. The imaging findings dramatically subsided.

Fig 13: Lymphoma involving bilateral lacrimal glands. On T2W FS coronal image arrows indicate soft tissues filling and expanding bilateral lacrimal glands.

Fig 14: ADC map showing diffusion restriction of both lacrimal glands(arrows), a helpful sign to differentiate lymphoma from inflammatory pathologies.

Extraocular Muscles(EOM):

Inflammation of the EOM is called myositis. Symptoms include pain with eye motion, diplopia, strabismus. One or more of the EOM may be involved uni/bi-laterally. Causes include IOI, IgG4-RD, sarcoidosis, thyroid eye disease (TED), and granulomatosis with polyangiitis.

Imaging: MRI shows enlarged, enhancing muscles. Metastases and lymphoma are important mimickers of myositis. The presence of signs of surrounding cellulitis and pain, and absence of diffusion restriction are suggestive of inflammation or infection. Low-flow caroticocavernous fistula(CCF) may also mimic myositis, with venous congestion leading to EOM enlargement. Enlarged superior ophthalmic veins are typically seen in CCF.

Fig 15: Myositis of the left medial rectus muscles, as shown by an expanded muscle with increased signal on T2W image(arrow). The patient had the diagnosis of IOI.

Fig 16: Post treatment image shows resolution of the findings.

Fig 17: T2W FS axial image shows an increased signal and size in the left lateral rectus muscle (arrow). Idiopathic orbital inflammation, IgG-4 disease, sarcoidosis, and hematologic malignancies were suggested as differentials. The patient was later diagnosed with B-cell acute lymphoblastic leukemia.

The remaining section will discuss orbital infection and common causes of orbital inflammation.

Orbital Infection:

Orbital infection is a common orbital pathology in the clinical practice. It's comprised of three clinical entities; preseptal cellulitis, orbital(posterior) cellulitis and endophthalmitis. The most important distinction is between preseptal cellulitis and orbital cellulitis. If the infection involves the tissues posterior to orbital septum, it's called orbital cellulitis which is treated with IV antibiotics. Etiologies include contiguous spread from dental-face infection, sinusitis, trauma, ocular surgery. 

Imaging: CT is the preferred modality. 

•Preseptal cellulitis: Soft tissue thickening anterior to the septum.

•Orbital cellulitis: Fat stranding, EOM enlargement, and possible subperiosteal/orbital abscess. 

Fig 18: A case of orbital cellulitis. Diffuse enhancement is seen in the left extraconal fatty tissues indicating orbital cellulitis. Accompanying collection in the superior extraconal space that is consistent with subperiosteal abscess(red arrow).

Fig 19: The same patient as in Fig. 18. There is soft tissue that has restricted diffusion in the left maxillary sinus, compatible with purulent material in this clinical scenario.

IOI:

IOI is an idiopathic inflammatory condition that can involve any orbital compartment, commonly involving multiple sites at the same time. Generally it's unilateral, but bilateral involvement is common. It's a diagnosis of exclusion; tumors, infection, or systemic diseases must be excluded. Clinical presentation is with rapid onset painful diplopia and proptosis. It is classified according to the compartment involved.

Imaging:  

On MRI, infiltrative masses show hyperintense areas on T2-weighted imaging, indicating active inflammation, and hypointense areas, suggesting fibrosis. Contrast enhancement is present. EOM involvement causes tubular enlargement, including the tendinous insertions, distinguishing it from TED. Lymphoma, which may closely mimic IOI, is often bilateral, steroid-resistant, has progressive clinical course, shows lower ADC values. IOI can involve orbital apex, mimicking Tolosa-Hunt syndrome; unlike Tolosa-Hunt, it spares the cavernous sinus.

Fig 20: A case of IOI. T1W post contrast coronal image shows diffuse infiltrating enhancing tissue in the left superior and lateral extraconal fat planes(red arrow) that extends to superficial fatty tissues lateral to the orbit(green arrow).

IgG4-RD:

IgG4-RD is a systemic inflammatory disease affecting orbital structures. It has a chronic, indolent course, typically without pain. The lateral rectus is the most commonly involved EOM, unlike IOI and TED, which usually affect the medial rectus. The lacrimal gland is the second most frequently involved structure. Nerve involvement may cause nerve enlargement, and orbital fat inflammation can occur. Although elevated serum IgG4 supports diagnosis, levels may be normal in many cases. Histopathology remains the diagnostic gold standard.

Fig 21: A case of IgG4-RD. T1W post contrast coronal image shows bilateral enhancing soft tissues in the superior and lateral extraconal spaces that also involve lacrimal gland, causing lacrimal gland enlargement.

TED:

Thyroid eye disease (TED) is the leading cause of adult proptosis, commonly linked to Graves disease, but also seen in Hashimoto thyroiditis. It can present before thyroid dysfunction symptoms or abnormal thyroid tests.

Extraocular muscles (EOM), often bilaterally, are most affected, typically involving the levator palpebrae superior, inferior rectus, medial, superior, lateral rectus, and oblique muscles (I'M SLOw). TED causes fusiform EOM enlargement sparing anterior tendons, known as the coca-cola bottle sign.

Orbital fat increase and dacryoadenitis may occur. Muscle enlargement and fat proliferation can crowd the orbital apex, risking optic nerve compression and optic neuropathy.

Fig 22: A case of TED. T2W axial image shows enlargement and increased signal of the right lateral and medial rectus muscles, that spares anterior tendinous portions with the so-called "coca cola" bottle sign.

Tolosa-Hunt Syndrome:

Tolosa-Hunt syndrome is an uncommon idiopathic inflammatory condition that is one of the causes of so-called "orbital apex syndrome". Clinical signs are related to involvement of the II., III., IV., V1 of V. and VI. cranial nerves. A variety of conditions from trauma, infection, aneurysms to tumors may cause those symptoms. Therefore conditions such as those must be excluded before diagnosing Tolosa-Hunt syndrome.

On MRI, there may be signs of inflammation in the cavernous sinus such as asymmetric enlargement and enhancement following contrast administration.

Fig 23: A case of Tolosa-Hunt Syndrome. T1W axial post contrast image shows asimetric thickening and enhancement of the anterior part of the right cavernous sinus(red arrow).

Sarcoidosis:

Sarcoidosis is a non-caseating granulomatous multisystemic disease . Orbital involvement is quite common and the most common manifestation is uveitis. Other soft tissues of the orbit, optic nerve and lacrimal gland can also be involved. Involvement is typically bilateral.

Fig 24: A case of sarcoidosis. T1W axial post contrast image shows asymmetrical thickening and enhancement of the right lower eyelid(red arrow). Histopathological analysis showed characteristic non-caseating granulomas.

Granulomatosis with Polyangiitis(GPA):

GPA is a necrotizing granulomatous c-ANCA positive small vessel vasculitis. It most commonly affects lungs, paranasal sinuses and kidneys. Orbital involvement is usually unilateral. CT features include proptosis, diffuse inflammatory soft tissue and paranasal sinuses are usually affected. GPA lesions in orbit  are usually hypointense on MRI.

Fig 25: A case of GPA. Axial contrast enhanced CT image shows bilateral diffuse soft tissues that replace nearly all of the fat in the orbits, causing bilateral proptosis with accompanying signs of destructive sinusitis.

Idiopathic sclerosing orbital inflammation (ISOI):

Previously thought to be the endstage of IOI, it is now considered a distinct pathologic entity with marked fibrosis present early in the disease. On imaging, ISOI manifests as an ill-defined mass, slightly enhancing, hypointense on T2-WI, and with no DWI restriction. Enophthalmus can exist due to the fibrotic process. The diagnosis of ISOI depends largely on biopsy.

Fig 26: A case of ISOI. T2W coronal image shows a hypointense soft tissue that is located in the right inferior-medial extraconal space(red arrow).

Fig 27: The same patient as in Fig. 26. The soft tissue shows enhancement following contrast administration(red arrow).