12

Orbital Inflmmation

Evana Valenzuela Scheker and C. Robert Bernardino

INTRODUCTION

Orbital inflammatory disease (OID) is a general term encompassing all inflammatory diseases that affect some or all of the structures contained within the orbit external to the ocular globe. In rare cases, the areas involved by the inflammatory process may extend beyond the orbit, such as into the cavernous sinus through the orbital apex or to the eyelids through the orbital septum. OID needs to be differentiated from neoplastic and infectious processes that may have similar presentation.

Pain is a prominent complaint in OID. Involvement of the extraocular muscles can result in diplopia. Lacrimal gland involvement often results in painful superolateral orbital swelling, while generalized orbital tissue involvement may present with proptosis, chemosis, periorbital or lid swelling, and, in severe cases, loss of vision due to optic nerve compression.

PATIENT HISTORY

Patients typically complain of periorbital pain, diplopia, a “bug-eyed” appearance, ocular injection, grittiness, and tearing. In advanced cases in which optic nerve compression is present, the patient may have altered color perception, enlarged blind spot, transient complete visual loss, or a visual field defect (Fig. 12.1A and B).

The examination of patients with orbital pain includes attention to the following:

• A full ophthalmic assessment of the anterior and posterior segments
  
• Orbital assessment including exophthalmometer measurements
  
• Determination of lid retraction
  
• Assessment for lid lag/lagophthalmos
  
• Evaluation for limitation of extraocular muscles
  
• Examination for signs of corneal exposure
  
• An assessment of optic nerve function, testing for an afferent papillary defect visual field aberration and dyschromatopsia

In general, diagnostic tools useful in the evaluation of OID include

• CBC—an elevated white blood cell count can suggest infection
  
• Inflammatory markers
  
  
  
  • Erythrocyte sedimentation rate (ESR)
    
  • C-reactive protein (CRP)

• Thyroid function panel
  
• Antithyroid antibodies
  
• Antineutrophil cytoplasmic antibodies (ANCA)
  
• Urinalysis—proteinuria suggests a systemic vasculitis with renal involvement
  
• Imaging (to help guide therapy)

Overall, imaging is helpful in differentiating between thyroid-associated ophthalmopathy and OID. In addition, the appearance of OID may overlap with that of malignant processes, in which case orbital biopsy is recommended.

Computed tomography (CT) scanning offers better visualization of bone, calcification, and acute hemorrhage.

Magnetic resonance imaging (MRI) with contrast and fat suppression is generally the preferred modality to image the orbit, and will demonstrate subtle inflammatory changes in nerves and muscles.

1. Imaging—inflammation and infiltration of involved orbital structures including the extraocular muscles, lacrimal gland, retrobulbar fat, and sometimes the sclera as well. There may be intracranial extension via the orbital apex or superior orbital fissure and involvement of the cavernous sinus. If extraocular muscles are involved, it involves the entire muscle including the tendinous insertions, resulting in a more tubular appearance on imaging. Diffuse IOI may result in inflammatory “streaking” of the orbital fat; it could be reminiscent of lymphoma. Atypical bony involvement should alert to the possibility of an infectious or malignant process.
   
2. CT—enlargement of the involved structures, streakiness in the adjacent fat, and enhancement post administration of contrast. There may be separate soft-tissue nodules.
   
3. MRI—enhancement in areas of involvement. T2-weighted images are iso- or hyperintense to that of extraocular muscles but are often less hyperintense than other orbital diseases due to the cellular nature of the infiltrate. Involved areas show moderate enhancement with gadolinium. Enhancement often correlates with disease activity and therefore a lower signal corresponds to disease that is less responsive to therapy. There may be thickening and enhancement of the posterior episclera. The lacrimal gland can have diffuse enlargement without alteration of its structure.
   
4. Echography—low to medium reflectivity, regular acoustic structure, and weak sound attenuation. Edema in Tenon capsule may appear as an area of lucency behind the globe.

• Dacryoadenitis: localized inflammation of the lacrimal gland
  
• Presentation: painful, firm, upper temporal orbital mass often associated with ptosis or S-shaped deformity (Fig. 12.2A,B–C)
  
• Differential diagnosis: sarcoidosis, Sjögren syndrome, lymphoma, or primary glandular tumor
  
• Myositis: acute or subacute inflammation of extra-ocular muscles

This entity is described in detail in Chapter 11. It is, in short, hyperemia of the fibrous coat that surrounds the sclera and is frequently seen associated with OID.

Scleritis

Also discussed in Chapter 11, this is inflammation of the sclera proper. Pain is generally the hallmark of the presentation. B-scan ultrasonography will show fluid in the episcleral space adjacent to the scleral inflammation.

Tolosa-Hunt Syndrome (THS)

This is idiopathic granulomatous inflammation of the cavernous sinus and superior orbital fissure. The condition affects structures traversing the cavernous sinus and may also affect the optic nerve. Some cases of IOI may extend to the cavernous sinus resulting in some overlap with THS.

Clinical Presentation

• Acute, unilateral orbital pain.
  
• Deficits of the third, fourth, fifth, or sixth cranial nerves may coincide with the onset of pain or develop subsequently up to 2 weeks later.

Diagnostic Criteria

• Steady, gnawing pain behind the eye with ophthalmoplegia.
  
• Involvement of nerves running the cavernous sinus.
  
• Duration of symptoms for days to weeks.
  
• Spontaneous remission with residual deficit.
  
• Recurrent attacks at intervals of months or years.
  
• Exclusion of all other disease processes.

Hunt and colleagues suggested responsiveness to corticosteroid treatment as a diagnostic indicator, although recent reports have cautioned against using this clinical pattern as a diagnostic criterion. Life-threatening diseases, such as lymphoma, aneurysm, and cavernous sinus metastasis, may be missed if corticosteroid responsiveness is considered pathognomonic for this syndrome.

Imaging

CT only excludes bony erosion but may not differentiate THS from other causes of inflammation MRI may be more sensitive for cavernous sinus pathology. It shows an enhancing cavernous sinus soft tissue mass that tends to resolve after corticosteroid therapy.

Treatment

THS responds favorably and rapidly to corticosteroids, but at least half of patients will experience recurrences, sometimes in the contralateral side. For this reason, patients typically require at least 2 years of follow-up and therapy before the disease process subsides.

Differential Diagnosis, Causes of Granulomatous Orbital Inflammation

• Tuberculosis (TB)
  
• Syphilis
  
• Sarcoidosis
  
• Wegener granulomatosis (WG)
  
• Malignant tumor like lymphoma and carcinoma
  
• Ruptured dermoid cyst
  
• Foreign body
  
• Blunt orbital trauma
  
• Idiopathic

Clinical Manifestation (Fig. 12.3A)

• Lid retraction (hallmark of the disease)
  
• Dry eyes
  
• Foreign body sensation
  
• Photosensitivity
  
• Exophthalmos
  
• Lid lag
  
• Restricted extraocular movement

Acute Phase

• Conjunctival injection
  
• Chemosis
  
• Lid edema
  
• Corneal exposure
  
• Optic nerve compression (rare)
  
• Less than 5% suffer from intense pain, diplopia, or vision loss

Hyperthyroidism

Hyperthyroidism is frequent

• Nervousness
  
• Tremor
  
• Fatigue
  
• Heat intolerance
  
• Diaphoresis
  
• Palpitations
  
• Weight loss
  
• Hair thinning
  
• Roughly 10% of patients will be euthyroid in presentation

• TED is a clinical diagnosis. Imaging studies and blood abnormalities can support a clinical diagnosis.
  
• Increased fat lucency, increased amount of orbital fat.
  
• Extraocular muscle enlargement sparing the insertions and origins (Fig. 12.3B and C).
  
• Muscle involvement—first inferior rectus, followed by medial, superior, and lateral recti muscles. Oblique muscles are rarely involved. Therefore isolated rectus muscle involvement should suggest other diagnoses such as myositis, or infiltrative diseases like lymphoma.

Imaging

• CT: Helps evaluate bony orbital anatomy for planning surgical interventions. Also helps evaluate the orbital apex in relationship to enlarged rectus muscles.
  
• MRI: T1 isointense and T2 isointense to slightly hyperintense to muscle. It is useful at assessing optic nerve compression due to thyroid-associated orbitopathy. It can predict response to therapy.
  
• Low T2 signal corresponds to a more fibrotic form, which is less responsive to therapy.
  
• Echography: Thickened muscle to medium to high internal reflectivity and an irregular acoustic structure.

Pathology

Early histopathology will show inflammatory cell infiltration, glycosaminoglycan deposition, and increased water content, resulting in variable amounts of extraocular muscle enlargement and orbital adipose tissue expansion. Variable amounts of edema and infiltration with inflammatory round cells.

Tumor necrosis factor-alpha and other proinflammatory cytokines are prominent in orbital tissue and may be involved in the stimulation of glycosaminoglycan synthesis.

Treatment

Thyroid dysfunction should be stabilized. However, normalization of thyroid function is not associated with reversal of eye disease. If active hyperthyroidism is present, the use of antithyroid medications (propylthiouracil and methimazole) is indicated. Radioactive iodine therapy is associated with worsening orbital inflammation and is generally avoided in patients with moderate to severe eye disease. Concomitant use of corticosteroids may prevent exacerbations. Surgical thyroidectomy is not associated with worsening TED, and therefore indicated for hyperthyroidism poorly controlled with medications and in the presence of TED.

Ocular disease is managed with symptomatic therapy until the disease stabilizes. Systematic corticosteroids and/or radiotherapy for acute orbital inflammation and congestion may be of benefit.

Mild Disease

• Intensive ocular lubricants/artificial tears
  
• Topical corticosteroids for chemosis

Moderate to Severe Disease

• The use of corticosteroids or radiotherapy is controversial.
  
• Both appear equally effective.
  
• Use of corticosteroid-sparing agents such as methotrexate after good response with corticosteroids but unable to taper off corticosteroids or having severe side effects from corticosteroid use.
  
• Eyelid recession, strabismus surgery, or orbital decompression after stabilization to improve function and cosmesis.
  
• Orbital decompression: urgent indication if TED that continues to progress despite corticosteroid use or irradiation, especially when there is of vision loss (either by corneal exposure or compressive optic neuropathy).
  
• Correction of residual proptosis, followed by lid or strabismus surgery during the inactive phase, after the disease remains unchanged for greater than 6 months. The order of surgeries should be decompression followed by strabismus surgery and finally eyelid surgery.

WG is the most common systemic vasculitis affecting the orbit. Other diseases, including Churg-Strauss syndrome, polyarteritis nodosa, and giant cell arteritis, have occasionally been implicated as well. WG is discussed in greater detail in Chapter 15.

Diagnosis

The diagnosis of WG is based on

• Biopsy for granulomatosis and necrotizing inflammation in the respiratory system
  
• Biopsy verified necrotizing vasculitis in small- to medium-sized vessel or glomerulonephritis or positive ANCA testing (see Chapters 4 and 15)

Imaging in WG-associated orbital disease shows diffuse orbital mass or masses that may be bilateral and may involve the adjacent nasopharynx.

MRI can depict granulomas and better delineate mucosal inflammation and ulceration in the sinuses, nasal cavity, and orbits. Most commonly, extension of sinonasal involvement is associated with osseous destruction.

Differential Diagnosis

• Bacterial and fungal orbital inflammatory infiltration
  
• Lymphoma of the orbit
  
• Sarcoidosis
  
• TED
  
• Orbital pseudotumor

Treatment

• Medical therapy as discussed in Chapter 19.
  
• Orbital decompression is indicated in cases of severe orbital inflammation with proptosis, especially in case of optic nerve impairment. Occasionally, the orbital inflammation is refractory to therapy despite successful management of disease elsewhere.

Temporal Arteritis (TA) or Giant Cell Arteritis

TA classically appears in patients of at least 50 years of age with new-onset headache, jaw claudication, scalp tenderness, anterior ischemic optic neuropathy, myalgias, fatigue, and weight loss. Temporal artery tenderness and elevated sedimentation rate are characteristic.

Ocular Manifestations

Neuro-ophthalmic manifestations include posterior ischemic optic neuropathy, central retinal or cilioretinal artery occlusion, and cranial neuropathies. Orbital manifestations include orbital ischemic syndrome and, very rarely, orbital inflammation. Orbital inflammation causes include periocular pain, decreased vision, and proptosis. Reported sites of orbital involvement include the extraocular muscles, optic nerve sheath, and intraconal fat. It is important to highlight the utility of temporal biopsy in the face of an inaccessible orbital mass.

Criteria for the Diagnosis

• Age at disease onset more than 50 years.
  
• New onset or type of localized head pain.
  
• Temporal artery tenderness or decreased pulsation.
  
• ESR >50 mm/hour (Westergren). Elevated CRP and platelet count is also seen. A rule of thumb is a normal ESR is half a patient’s age in males or half the age plus 10 in females.

Biopsy

Temporal artery biopsy should be obtained, with a biopsy specimen at least 20 mm in length. It is conventional, though not strictly necessary, to biopsy the temporal artery on the more clinically affected side of the head. Note that patients are generally started on empiric corticosteroid therapy as soon as TA is suspected, and we feel that 7 days is the longest one may wait before obtaining a biopsy in this situation. Histopathologic findings of TA include vasculitis characterized by any of the following:

This disease is discussed in detail in Chapter 15. Most cases of orbital sarcoid are discrete orbital masses, usually in the inferior quadrants of the orbit. These are more common in patients with active systemic sarcoidosis. Within the orbit, sarcoidosis can involve the lacrimal gland, soft tissue of the orbit, and the optic nerve (Fig. 12.4A and B). Orbital soft tissue involvement is distinctly uncommon. In one large series, orbital involvement was seen in 1% of patients with ophthalmic manifestations. In two other series, none were reported. Inferior orbit is the most commonly reported in cases with orbital involvement. Extraocular muscle involvement may be seen in association with orbital lesions (especially in cases of diffuse involvement), but solitary muscle enlargement secondary to sarcoidosis is rare with only a few cases reported. It mimics other orbital inflammatory syndromes with acute or subacute inflammation.

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