There are a number of orbital inflammatory processes that are important in the differential diagnosis of orbital tumors. The most important of these are thyroid-related ophthalmopathy (TRO) and idiopathic nongranulomatous orbital inflammation (INOI) (“inflammatory pseudotumor”). In addition, there are a number of bacterial, fungal, and idiopathic granulomatous disorders that can occur in the orbit.

TRO is a common autoimmune disorder usually associated with hyperthyroidism. The diverse nomenclature for this intriguing entity has been confusing and inconsistent and includes Graves disease, Graves orbitopathy, Graves ophthalmopathy, thyroid eye disease, thyroid orbitopathy, thyroid ophthalmopathy, dysthyroid orbitopathy, dysthyroid ophthalmopathy, thyroid-related orbitopathy, thyroid-associated orbitopathy, and thyroid-associated ophthalmopathy. We have chosen to use the term “thyroid-related ophthalmopathy” because the condition is related to thyroid dysfunction and affects other ocular structures (eyelids, conjunctiva) in addition to the orbit.

TRO typically affects the extraocular muscles and has rather characteristic features. In some cases, it can simulate a neoplasm clinically and radiographically. Numerous chapters and articles have addressed the clinical features, pathogenesis, pathology, and management of TRO; only some of the more recent or more important ones are cited here (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17).

Clinically, the patient with TRO usually shows characteristic unilateral or bilateral proptosis, eyelid retraction, eyelid lag on downgaze, eyelid edema, and conjunctival hyperemia and edema. In more advanced cases, the patient can develop diplopia, exposure keratopathy, and optic disc edema owing to compression of the optic nerve in the orbit (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17).

Although there are many laboratory tests to assess thyroid gland function and diagnose TRO, the main ones used by most clinicians are tri-iodothyronine, total and free thyroxin, and thyroid-stimulating hormone. Orbital imaging studies have become highly reliable methods of diagnosing TRO. Computed tomography (CT) and magnetic resonance imaging (MRI) show characteristic enlargement of rectus muscles without appreciable involvement of the muscle tendons and orbital fat. Ultrasonography has been largely replaced by these superior imaging techniques (1).

On surgical inspection or gross examination, the extraocular muscles are enlarged, firm, and rubbery. Histopathology reveals infiltration of the affected enlarged muscles by lymphocytes, plasma cells, and scattered mast cells (1,4).

Depending on the severity of the disease and the complications, management of TRO can include observation, corticosteroids, radiotherapy, tarsorrhaphy, and orbital decompression. These treatment approaches are discussed in detail in the literature (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17).

Acute orbital cellulitis is an infection of the soft tissues of the orbit and adjacent structures. It can affect children or adults. It most commonly occurs as a result of infectious extension from the ethmoid or frontal sinuses (1,2,3,4,5,6,7,8). However, it can also develop by contiguous spread from sites of trauma or infection, including dacryocystitis and conjunctivitis. Mucocele and mucopyocele, which can also extend into the orbit from the sinuses, are discussed in Chapter 27. Infectious orbital inflammation has been classified into five categories (1):

Group 1: Preseptal cellulitis

Group 2: Orbital cellulitis

Group 3: Subperiosteal abscess

Group 4: Orbital abscess

Group 5: Cavernous sinus thrombosis

Based on traditional terminology, we use the umbrella term “orbital cellulitis” to include all of these categories. Although the classification suggests an orderly progression, that is not necessarily the case and clinical onset can vary considerably.

The clinical findings in orbital cellulitis vary with the inciting cause and the category and severity of the disease. The patient can present with any combination of pain, eyelid edema, conjunctival hyperemia, discharge, proptosis, displacement of the globe, and diplopia. Cavernous sinus thrombosis (group 5) can induce severe symptoms and was often fatal before the advent of antibiotics. In some instances, an orbital abscess can be localized and simulate a cyst or neoplasm. In a child, rhabdomyosarcoma and other malignant tumors can produce inflammatory signs and should be considered in the differential diagnosis (4). It should also be remembered that necrotic retinoblastoma can cause secondary inflammatory signs and simulate orbital cellulitis (7,8).

History and physical examination should be directed toward detecting an inciting cause. Imaging studies like computed tomography and magnetic resonance imaging can detect primary infection of the sinuses, determine the extent of the orbital disease, and allow classification of the infectious process.

The pathology of orbital cellulitis varies with the cause of the infection and the inciting organism. Histopathologically, the tissues are infiltrated or replaced by acute and chronic inflammatory cells and the inciting organisms can often be identified. Most common organisms include Streptococcus species, Staphylococcus aureus, and Staphylococcus epidermidis. Haemophilus influenza was previously the most common cause, especially among children. However, it has become uncommon since the introduction of specific vaccines.

Treatment generally involves microscopic study and cultures of the discharge and appropriate antibiotic therapy (2). Surgical drainage is often helpful. The prognosis is generally good unless severe cavernous sinus thrombosis develops.

“Nonspecific orbital inflammation (NOI)” is traditionally used to describe a nongranulomatous inflammatory process within the orbit that has no demonstrable cause (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21). The term “pseudotumor” is sometimes applied to this condition. However, that term can apply to any lesion that simulates a neoplasm, including granulomatous inflammation, abscess, and amyloidosis. Therefore, we prefer to avoid “pseudotumor,” and prefer to call this condition idiopathic nongranulomatous orbital inflammation (INOI). There is considerable confusion regarding this condition and the definition, terminology, and classification will most certainly change as it is better understood and more specific etiologies are identified.

In the authors’ series of 1,264 orbital masses, the 98 cases of INOI accounted for 74% of inflammatory-infectious diseases and for 8% of all orbital lesions (1). In a study of orbital tumors in older patients, it accounted for 8% of lesions among patients .60 years of age (17). INOI can affect both adults and children (5). The mean age at diagnosis is about 45 years with an age range of 2 to 92 years. About 25% are bilateral (10). Depending on the tissues involved and the orbital location, INOI has been divided into subcategories, including myositis, dacryoadenitis, anterior, diffuse, and posterior (apical) (3).

The clinical features of INOI vary with the subcategory of the disease. Myositis affects one or more rectus muscles and produces a rather acute onset of pain that is worse with eye movements, and injection of the muscle insertion. Central vision is usually good. Dacryoadenitis shows superotemporal eyelid and conjunctival swelling, pain, and a tender mass in the lacrimal gland area. The central vision is usually good. The anterior variant is characterized by pain, eyelid edema, conjunctival chemosis, and limitation of ocular motility. Affected patients can have signs of diffuse uveitis and retinal detachment, findings similar to Harada disease. The diffuse variant demonstrates symptoms and signs similar to the anterior variety. However, the findings are more severe and proptosis is more pronounced. The apical variant of INOI causes more severe pain, visual loss, and motility disturbance, but less anterior segment inflammation. The pain is particularly severe with ocular movement. The painful ophthalmoplegia is similar to the Tolosa-Hunt syndrome.

In some instances, INOI can extend beyond the orbit into the paranasal sinuses and brain. Some such patients may have only minimal symptoms and signs to suggest neurologic extension, but it can be recognized on neuroimaging (18). Severe cases can rarely present with central retinal artery and vein obstruction secondary to compression of the globe (19).

The differential diagnosis of INOI includes a variety of inflammatory and neoplastic conditions. Myositis can closely resemble thyroid-associated orbitopathy or metastatic carcinoma. Any variant must be differentiated from lymphoma, metastatic carcinoma, and other circumscribed or diffuse orbital masses.

Findings on computed tomography and magnetic resonance imaging vary with the location and extent of involvement. Myositis shows enlargement of one or more rectus muscles, often with involvement of the muscle tendons, a finding that helps to differentiate it from thyroid-related orbitopathy. Dacryoadenitis shows enlargement of the lacrimal gland and inflammatory signs and may cause findings similar to a ruptured dermoid cyst. Anterior and diffuse involvements show an ill-defined mass and choroidal thickening and retinal detachment. The apical variant shows a diffuse or ill-defined mass at the orbital apex with compression of nerves and muscles. As mentioned, neuroimaging studies can sometimes detect extraorbital extension of INOI (18). In patients with classic symptoms and signs, an orbital biopsy is generally not indicated unless the lesion fails to respond to medical therapy (see Management).