The exact cause of IOI is unknown, but infectious and immune-mediated mechanisms have been proposed. Several studies have described cases where onset of orbital pseudotumor was seen simultaneously or several weeks after upper respiratory infections. Another study by Wirostko et al. proposes that organisms resembling Mollicutes cause orbital inflammation by destroying the cytoplasmic organelles of parasitized cells.

Orbital pseudotumor has also been observed in association with Crohn’s disease, systemic lupus erythematosus, rheumatoid arthritis, diabetes mellitus, myasthenia gravis, and ankylosing spondylitis all of which strengthen the basis of IOI being an immune-mediated disease. Response to corticosteroid treatment and immunosuppressive agents also support this idea.

Trauma has also been seen to precede some cases of orbital pseudotumor. However, one study by Mottow-Lippe, Jakobiec, and Smith suggests that the release of circulating antigens caused by local vascular permeability triggers an inflammatory cascade in the affected tissues.

Although these mechanisms have been postulated as possible causes of IOI, their exact nature and relationships to the condition still remain unclear.

IOI or orbital pseudotumor is the second most common cause of exophthalmos following Grave’s orbitopathy and the third most common orbital disorder following thyroid orbitopathy and lymphoproliferative disease accounting for 5–17.6% of orbital disorders, There is no age, sex, or race predilection, but it is most frequently seen in middle-aged individuals. Pediatric cases account for about 17% of all cases of IOI.

IgG4-related ophthalmic disease (IgG4-ROD) is the recommended term to describe orbital (eye socket) manifestations of the systemic condition IgG4-related disease, which is characterised by infiltration of lymphocytes and plasma cells and subsequent fibrosis in involved structures. It can involve one or more of the orbital structures.

Frequently involved structures include the lacrimal glands, extraocular muscles, infraorbital nerve, supraorbital nerve and eyelids. It has also been speculated that ligneous conjunctivitis may be a manifestation of IgG4-related disease (IgG4-RD).

As is the case with other manifestations of IgG4-related disease, a prompt response to steroid therapy is a characteristic feature of IgG4-ROD in most cases, unless significant fibrosis has already occurred.

Symptoms, if any, can be mild even in the presence of significant swelling or masses.

Lacrimal gland involvement may cause swelling of the upper eyelid, or proptosis if there is severe swelling. Other orbital masses or inflammation can result in visual disturbance (blurred vision, double vision, visual field impairment), restricted eye movements, pain or discomfort, numbness in the distribution of the supraorbital and/or infraorbital nerves, or proptosis.

IgG4-related ophthalmic disease has been estimated to account for approximately 25% of all cases of proptosis, eyelid swelling and other features of orbital swelling.

This is an uncommon lesion, usually affecting young patients (mean age, 30 years), with a male to female ratio of 2:1. The middle ear is involved, although it may extend to the external auditory canal if there is tympanic membrane perforation.

Scleritis is not a common disease, although the exact prevalence and incidence are unknown. It is somewhat more common in women, and is most common in the fourth to sixth decades of life.

An otic polyp (also called aural polyp) is a benign proliferation of chronic inflammatory cells associated with granulation tissue, in response to a longstanding inflammatory process of the middle ear.

Risk factors of progressive and severe thyroid-associated orbitopathy are:

- Age greater than 50 years

- Rapid onset of symptoms under 3 months

- Cigarette smoking

- Diabetes

- Severe or uncontrolled hyperthyroidism

- Presence of pretibial myxedema

- High cholesterol levels (hyperlipidemia)

- Peripheral vascular disease

Trochleitis is diagnosed based on three criteria: 1) demonstration of inflammation of superior oblique tendon/ trochlea region, 2) periorbital pain and tenderness to palpation in the area of the sore trochlea, and 3) worsening of pain on attempted vertical eye movement, particularly with adduction of the eye. It is important to identify trochleitis because it is a treatable condition and the patient can benefit much from pain relief. Treatment consists of a single injection of corticosteroids to the affected peritrochlear region. A specific "cocktail" consisting of 0.5 ml of depomedrol (80 mg/ml) and 0.5 ml of 2% lidocaine can be injected into the trochlea; immediate relief due to the effects of the local anesthetic indicates successful placement. However, great care must be taken as the injection is in the region of several arteries, veins and nerves. The needle should not be too small (so as not to penetrate tiny structures), the surgeon should draw back on the syringe (to ensure not have pierced a vessel), the lidocaine should not contain epinephrine (which could cause vasospasm), and the pressure of the injection must always be controlled. Only a limited number of injections can be made as they would otherwise lead to muscle atrophy. Diagnosis can be confirmed by response to this treatment; pain and swelling are expected to disappear in 48–72 hours. Some patients experience recurrence of trochleitis.

Bacterial infections of the orbit have long been associated with a risk of catastrophic local

sequelae and intracranial spread.

The natural course of the disease, as documented by Gamble (1933), in the pre-antibiotic era,

resulted in death in 17% of patients and permanent blindness in 20%.

The prognosis of THS is usually considered good. Patients usually respond to corticosteroids, and spontaneous remission can occur, although movement of ocular muscles may remain damaged. Roughly 30–40% of patients who are treated for THS experience a relapse.

Treatment of THS includes immunosuppressives such as corticosteroids (often prednisolone) or steroid-sparing agents (such as methotrexate or azathioprine).

Radiotherapy has also been proposed.

Most of the time, scleritis is not caused by an infectious agent. Histopathological changes are that of a chronic granulomatous disorder, characterized by fibrinoid necrosis, infiltration by polymorphonuclear cells, lymphocytes, plasma cells and macrophages. The granuloma is surrounded by multinucleated epitheloid giant cells and new vessels, some of which may show evidence of vasculitis.

The cause of trochleitis is often unknown (idiopathic trochleitis), but it has been known to occur in patients with rheumatological diseases such as systemic lupus erythematosus, rheumatoid arthritis, enteropathic arthropathy, and psoriasis. In his study, Tychsen and his group evaluated trochleitis patients with echography and CT scan to demonstrate swelling and inflammation. Imaging studies showed inflammation of superior oblique tendon/ trochlear pulley. It was unclear whether the inflammation involved the trochlea itself, or the tissues surrounding the trochlea.

The formation of gummata is rare in developed countries, but common in areas that lack adequate medical treatment.

Syphilitic gummas are found in most but not all cases of tertiary syphilis, and can occur either singly or in groups. Gummatous lesions are usually associated with long-term syphilitic infection; however, such lesions can also be a symptom of benign late syphilis.

Plasma cell granuloma is a lesional pattern of inflammatory pseudotumour, different from the "inflammatory myofibroblastic tumor" pattern.

It is linked to IgG4-related disease.

A foreign-body granuloma occurs when a foreign body (such as a wood splinter, piece of metal, glass etc.) penetrates the body's soft tissue followed by acute inflammation and formation of a granuloma. In some cases the foreign body can be found and removed even years after the precipitating event.

With respect to embolic and hemodynamic causes, this transient monocular visual loss ultimately occurs due to a temporary reduction in retinal artery, ophthalmic artery, or ciliary artery blood flow, leading to a decrease in retinal circulation which, in turn, causes retinal hypoxia. While, most commonly, emboli causing amaurosis fugax are described as coming from an atherosclerotic carotid artery, any emboli arising from vasculature preceding the retinal artery, ophthalmic artery, or ciliary arteries may cause this transient monocular blindness.

- Atherosclerotic carotid artery: Amaurosis fugax may present as a type of transient ischemic attack (TIA), during which an embolus unilaterally obstructs the lumen of the retinal artery or ophthalmic artery, causing a decrease in blood flow to the ipsilateral retina. The most common source of these athero-emboli is an atherosclerotic carotid artery. However, a severely atherosclerotic carotid artery may also cause amaurosis fugax due to its stenosis of blood flow, leading to ischemia when the retina is exposed to bright light. "Unilateral visual loss in bright light may indicate ipsilateral carotid artery occlusive disease and may reflect the inability of borderline circulation to sustain the increased retinal metabolic activity associated with exposure to bright light."

- Atherosclerotic ophthalmic artery: Will present similarly to an atherosclerotic internal carotid artery.

- Cardiac emboli: Thrombotic emboli arising from the heart may also cause luminal obstruction of the retinal, ophthalmic, and/or ciliary arteries, causing decreased blood flow to the ipsilateral retina; examples being those arising due to (1) atrial fibrillation, (2) valvular abnormalities including post-rheumatic valvular disease, mitral valve prolapse, and a bicuspid aortic valve, and (3) atrial myxomas.

- Temporary vasospasm leading to decreased blood flow can be a cause of amaurosis fugax. Generally, these episodes are brief, lasting no longer than five minutes, and have been associated with exercise. These vasospastic episodes are not restricted to young and healthy individuals. "Observations suggest that a systemic hemodynamic challenge provoke[s] the release of vasospastic substance in the retinal vasculature of one eye."

- Giant cell arteritis: Giant cell arteritis can result in granulomatous inflammation within the central retinal artery and posterior ciliary arteries of eye, resulting in partial or complete occlusion, leading to decreased blood flow manifesting as amaurosis fugax. Commonly, amaurosis fugax caused by giant cell arteritis may be associated with jaw claudication and headache. However, it is also not uncommon for these patients to have no other symptoms. One comprehensive review found a two to nineteen percent incidence of amaurosis fugax among these patients.

- Systemic lupus erythematosus

- Periarteritis nodosa

- Eosinophilic vasculitis

- Hyperviscosity syndrome

- Polycythemia

- Hypercoagulability

- Protein C deficiency

- Antiphospholipid antibodies

- Anticardiolipin antibodies

- Lupus anticoagulant

- Thrombocytosis

- Subclavian steal syndrome

- Malignant hypertension can cause ischemia of the optic nerve head leading to transient monocular visual loss.

- Drug abuse-related intravascular emboli

- Iatrogenic: Amaurosis fugax can present as a complication following carotid endarterectomy, carotid angiography, cardiac catheterization, and cardiac bypass.

Although the exact cause of this condition is not known, it is an inflammatory disorder characterised by collagen degeneration, combined with a granulomatous response. It always involves the dermis diffusely, and sometimes also involves the deeper fat layer. Commonly, dermal blood vessels are thickened (microangiopathy).

It can be precipitated by local trauma, though it often occurs without any injury.

Inflammatory myofibroblastic tumour is a lesional pattern of inflammatory pseudotumour, as plasma cell granuloma. It is abbreviated IMT.

Crohn's disease is an inflammatory condition of uncertain cause characterized by severe inflammation in the wall of the intestines and other parts of the abdomen. Within the inflammation in the gut wall, granulomas are often found and are a clue to the diagnosis.

Complications include hearing loss, blood infection, meningitis, cavernous sinus thrombosis, and optic nerve damage (which could lead to blindness).

The symptoms depend on the specific location of the tumour, which can be anywhere in the body.

Treatment usually involves surgical removal of the lesion down to the bone. If there are any adjacent teeth, they are cleaned thoroughly with scaling and root planing (SRP) to remove any possible source of irritation. Recurrence is around 10%.

Inflammatory issues associated with contact granuloma include gastroesophageal reflux, allergy or infection. There is some disagreement among researchers as to whether inflammatory issues are a direct cause. Some researchers identify reflux and infection as indirect causes due to aggressive coughing that usually occurs as a result.