INTRODUCTION — Scleritis is a painful, destructive, and potentially blinding inflammatory disorder of the sclera that may also involve the cornea, adjacent episclera, and underlying uveal tract. Scleritis has a striking, highly symptomatic clinical presentation (picture 1) (see 'Clinical features' below). By contrast, episcleritis is typically self-limited or quickly responsive to topical therapies. (See "Episcleritis".)
Scleritis sometimes occurs in an isolated fashion, without evidence of inflammation in other organs. However, in up to 50 percent of patients, scleritis is associated with an underlying systemic illness such as rheumatoid arthritis or granulomatosis with polyangiitis [1] (see 'Systemic disease associations' below). Two-thirds of patients with scleritis require high-dose glucocorticoids or the combination of high-dose glucocorticoids and another immunosuppressive agent to achieve disease control [2]. (See "Treatment of scleritis".)
This topic will review the clinical manifestations and diagnosis of scleritis. The treatment of scleritis, episcleritis, and issues related to other inflammatory disorders of the eye are presented separately. (See "Treatment of scleritis" and "Episcleritis" and "Uveitis: Etiology, clinical manifestations, and diagnosis" and "Ocular manifestations of rheumatoid arthritis" and "Retinal vasculitis associated with systemic disorders and infections".)
ANATOMY — The sclera lies beneath the conjunctiva and episclera but above the choroid (figure 1). The opaque scleral tissue is composed of collagen fibrils arranged in a precise, interlacing manner that enhances rigidity and stability. Although the sclera itself is avascular, the tissue derives its metabolic requirements by diffusion from the episclera and choroid, both of which are highly vascularized.
The sclera comprises 90 percent of the outer coat of the eye. Scleral tissue begins at the limbus (the outer edge of the cornea) and terminates posteriorly at the optic canal. At the posterior pole of the eye, the sclera fuses with the dura mater and arachnoid sheaths of the optic nerve. These anatomic relationships explain why optic nerve edema and visual compromise are common complications of posterior scleritis (picture 2). (See 'Clinical features' below.)
The sclera is divided into an anterior portion that is visible to the examiner and a posterior portion that lies behind the globe. Inflammation may occur in either the anterior or the posterior portion; rarely, it affects both, particularly in the setting of systemic inflammation. Anterior scleritis and posterior scleritis have different sets of implications for diagnosis, treatment and prognosis.
SCLERITIS SUBTYPES — Approximately 90 percent of scleritis cases involve the anterior portion of the sclera. Posterior scleritis is defined as involvement of the sclera by inflammation posterior to the insertion of the medial and lateral rectus muscles. Diffuse, nodular, and necrotizing subtypes of both anterior and posterior scleritis are recognized. (See 'Anterior scleritis' below and 'Posterior scleritis' below.)
Anterior scleritis — Anterior scleritis (picture 1) is subclassified into several subtypes:
●Diffuse anterior scleritis – Diffuse anterior scleritis is the most common and least severe form of scleritis, accounting for nearly 50 percent of cases (picture 3). Most cases respond to relatively mild therapies and do not recur. (See 'Clinical features' below and "Treatment of scleritis".)
●Nodular anterior scleritis – Nodular anterior scleritis is the second most common form of anterior scleritis, accounting for 20 to 40 percent of cases (picture 4). Multiple attacks of scleritis occur in approximately 50 percent of patients. (See 'Clinical features' below.)
●Necrotizing anterior scleritis – Necrotizing anterior scleritis is the least common but most dangerous subtype of anterior scleral inflammation. Compared with diffuse or nodular scleritis, this disorder occurs more frequently in women, has an older mean age of onset (average age 66 years), is more often associated with a systemic inflammatory illness, and is more likely to lead to ocular complications.
Necrotizing anterior scleritis is divided into two forms:
•Necrotizing anterior scleritis "with inflammation" – This form of necrotizing anterior disease is highly symptomatic, with florid inflammatory features (picture 5 and picture 6). (See 'Clinical features' below.)
•Scleromalacia perforans – Scleromalacia perforans, also known as necrotizing anterior scleritis "without inflammation," is a rare form of severe scleritis (picture 7). The majority of these patients have longstanding histories of systemic inflammatory illness, of which rheumatoid arthritis is the most common; it may also rarely occur in patients with granulomatosis with polyangiitis. (See 'Clinical features' below.)
Posterior scleritis — Diffuse, nodular, and necrotizing variants of posterior scleritis have also been identified, but the clinical distinction between these entities is more difficult due to anatomic challenges involved in the assessment of posterior scleritis [3,4].
Because of the delays inherent in diagnosing an inflammatory process focused behind the eye and the proximity of posterior scleral inflammation to sensitive ocular tissues (eg, the retina and optic nerve), posterior scleritis usually requires the types of intensive immunosuppressive therapy used in necrotizing anterior scleritis. (See "Treatment of scleritis".)
PATHOGENESIS
Pathophysiology — Inflammatory and autoimmune processes, particularly vasculitis, appear to play a role in the pathogenesis of scleritis in many patients. However, the precise steps in the pathophysiology of most forms of scleritis are not well-defined. About half of the patients with scleritis have an associated systemic inflammatory or autoimmune disorder, in which vasculitis or vasculopathy is known to occur (see 'Systemic disease associations' below). However, it is unknown in such patients why the eye is targeted. Similarly, inflammatory changes can occur in association with infectious causes as well, sometimes with disease due to direct effects of the infectious agent on the sclera.
An important underlying role for vasculitis in patients with necrotizing scleritis is illustrated by a study in which conjunctival and scleral biopsies from 25 patients with necrotizing scleritis and five with recurrent non-necrotizing scleritis were evaluated [5]. The patients had histopathologic evidence of vasculitis, with fibrinoid necrosis and neutrophil invasion of blood vessel walls and immune complex deposition in vessels from both scleral specimens, which include the episcleral tissue, and conjunctival specimens.
In rheumatoid vasculitis, which is often associated with necrotizing scleritis, immune complex deposition within the vessel wall leads to fibrinoid necrosis, thrombotic occlusion of blood vessels, and the generation of a chronic inflammatory response in the sclera [6]. The scleritis is usually characterized by granulomatous inflammation adjacent to or involving the scleral blood vessels.
Systemic disease associations — Scleritis is associated with a systemic disease in approximately 50 percent of cases, including systemic rheumatic and inflammatory disorders, such as rheumatoid arthritis (RA) and granulomatosis with polyangiitis; and infectious diseases, including herpes zoster (table 1).
The most common association is with RA. When scleritis complicates RA, it is generally considered to be a manifestation of rheumatoid vasculitis, heralding the need for an intensification of therapy. (See "Ocular manifestations of rheumatoid arthritis" and "Clinical manifestations and diagnosis of rheumatoid vasculitis" and "Treatment of rheumatoid vasculitis".)
Among the primary vasculitides, which are prominent among the other systemic disorders associated with scleritis, granulomatosis with polyangiitis, which may be either in a generalized or a limited form, is a much more common cause of scleritis than the other types of vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), such as microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (Churg-Strauss) [7].
A retrospective study of 243 patients at a tertiary referral center determined that nearly half of the patients (47 percent) had an underlying identifiable condition, most commonly a rheumatic disease (37 percent) or infection (7 percent) [8]:
●Among those with rheumatic disease, RA was the most common
●Among those with infection, herpes zoster was the most common
Interestingly, among the patients with an associated medical condition, only 78 percent had a diagnosis by the time of ocular disease presentation. Among those conditions that had not been diagnosed prior to the onset of eye disease, systemic vasculitides, including ANCA-related conditions, were the most common.
Local trauma may also be a contributing factor. Scleritis may first occur after ocular surgery, perhaps initiated by trauma to the sclera [9-11]. The risk may be greater in patients with underlying rheumatic disease [9,10].
CLINICAL FEATURES
Ocular symptoms — Scleritis is usually characterized by severe, constant, boring pain that worsens at night or in the early morning hours and radiates to the face and periorbital region. The extraocular muscles insert into the sclera, thus ocular movements exacerbate the pain associated with scleral inflammation. The pain generally limits activity and often prevents sleep. Additionally, patients may report headache; watering of the eye; ocular redness, particularly in patients with non-necrotizing anterior scleritis; and photophobia, which is variably present. Symptoms may vary depending upon the severity of scleritis that is present and whether there is tissue necrosis. When there is tissue necrosis in severe disease, there is loss of peripheral innervation which leads to "paradoxic" lessening of symptoms:
●Diffuse and nodular anterior scleritis – Diffuse and nodular anterior scleritis are the most common forms of scleritis and the clinical types most commonly associated with pain and discomfort as described above.
●Necrotizing anterior scleritis – Patients with necrotizing anterior scleritis may experience very severe symptoms, which can be seen in necrotizing anterior scleritis with inflammation; or minimal to no symptoms, as in scleromalacia perforans, also termed necrotizing anterior scleritis without inflammation:
•Necrotizing anterior scleritis with inflammation – Symptoms of necrotizing anterior scleritis with inflammation include severe ocular and periorbital pain that steadily worsens to excruciating levels over days or weeks. The pain is boring in quality, and usually worse in the early morning hours. There is also almost always some degree of tenderness over the inflamed eye which is often not present in many other cases of the "red eye."
•Scleromalacia perforans – Scleromalacia perforans, commonly bilateral, is characterized by a remarkable lack of symptoms, particularly an absence of pain, which is due to tissue necrosis and loss of nerves. The absence of pain results from the necrosis of pain fibers. Patients may notice a change in color of their sclera because of scleral thinning. They may also experience a decrease in vision caused by a change in the shape of the eyeball and an alteration of corneal curvature (an acquired astigmatism).
●Posterior scleritis – Symptoms of posterior scleritis may include variable amounts of pain (often severe) that is difficult to localize. Diplopia and pain upon eye movement are common. In addition, these patients may have reduced vision due to compression of the retina or optic nerve.
The findings on ophthalmologic examination depend upon the type, severity, and location of the scleritis. (See 'Ocular examination' below.)
Ocular examination — The essential sign of scleritis is edema, usually accompanied by violaceous discoloration of the globe and tenderness (picture 3 and picture 4). All vascular layers of the sclera may be involved, but the maximal involvement is in the deep episcleral vascular plexus, which is displaced outward by the edematous, swollen sclera. On slit-lamp examination, there is profound dilatation of the deep episcleral vascular plexus.
The different subtypes of scleritis are associated with variable presentations and distinctive findings on physical examination:
●Diffuse anterior scleritis – Diffuse anterior scleritis is associated with widespread ocular erythema and scleral edema but no nodules or areas of necrosis (picture 3). Only a small number of patients with diffuse anterior scleritis have disease that progresses to more aggressive forms.
●Nodular anterior scleritis – Localized areas of firm, tender edema associated with intense dilation of the deep episcleral vessels may be found in nodular anterior scleritis (picture 4). With treatment, the pain and scleral tenderness resolve rapidly; however, the nodules may persist for months.
●Necrotizing anterior scleritis – There are two types of necrotizing anterior scleritis, termed necrotizing anterior scleritis with inflammation and scleromalacia perforans.
•Necrotizing anterior scleritis with inflammation – Physical examination reveals scleral edema with intense vasodilatation of the deep episcleral plexus and superficial vessels (picture 5). With advanced disease, slit-lamp examination reveals obvious blood vessel closure associated with thinning of the sclera and a bluish discoloration, representing the underlying choroid visible through thinned scleral tissue (picture 6). Patients with this form of scleritis may also develop concurrent corneal ulceration and inflammation as a manifestation of peripheral ulcerative keratitis (PUK).
•Scleromalacia perforans – Examination of patients with scleromalacia perforans reveals thinning and atrophy of the episclera and loss of the normal episcleral vasculature. The anterior sclera develops localized tissue infarctions that have a yellowish-white color often referred to as "marbleized" (picture 7). Spontaneous perforation of the globe is rare, but reported.
Patients with scleromalacia perforans need to be followed closely so that appropriate surgical and medical measures (eg, patch grafting) may be undertaken to maintain globe integrity. (See "Treatment of scleritis", section on 'Role of surgery'.)
●Posterior scleritis – When posterior scleritis occurs in association with anterior scleritis, the eye is red. However, when posterior scleritis occurs in isolation, the eye is white. In this setting, the examiner may observe inflammation of parts of the posterior sclera only at extremes of the patient's gaze.
Signs of posterior scleritis include exudative retinal detachment, annular choroidal detachment, optic disc edema, retinal folds, choroidal folds, retinal vasculitis, posterior uveitis, and glaucoma (picture 2). (See "Treatment of scleritis", section on 'Course and prognosis'.)
Involvement of other ocular structures — In addition to the sclera, other ocular tissues may be involved in scleral inflammatory disease:
●Cornea – Chronic inflammation at the limbus can result in collagenolysis, epithelial ulceration, and the rapid development of PUK. In severe cases of PUK, the syndrome of "corneal melt" may lead swiftly to irreversible loss of vision in the eye [12]. (See "Ocular manifestations of rheumatoid arthritis", section on 'Corneal inflammation and melting'.)
●Uveal tract – Anterior uveitis occurs in up to 40 percent of eyes involved by scleritis and may lead to additional management considerations, eg, the use of glucocorticoid eyedrops. This is thought to be primarily a form of "spillover" inflammation, rather than a primary involvement of the uveal tract.
●Posterior segment – Posterior scleritis may be associated with vitreitis, cystoid macular edema, and exudative retinal detachment. (See "Treatment of scleritis", section on 'Course and prognosis'.)
●Lens – Cataract formation is related to the severity of the scleritis. It primarily occurs in necrotizing scleritis, affecting approximately 20 percent of such patients. The incidence of cataract is much lower (less than 5 percent) with other subtypes of scleritis. Glucocorticoid therapy may be a contributor to cataract formation. (See "Cataract in adults".)
Features of systemic disease — Although the ocular complaints and findings are the most prominent disease feature for many patients with scleritis, critical clues to the presence of a systemic inflammatory condition may be present on the general history and physical examination. (See 'Systemic disease associations' above.)
DIAGNOSIS — The diagnosis of scleritis has two major elements. These are the diagnosis of scleritis itself (see 'Diagnosis of scleritis' below) and the diagnostic evaluation to establish or exclude the presence of an associated systemic disorder (see 'Diagnostic evaluation for systemic disease' below). The latter evaluation can sometimes influence the approach to diagnosis and classification of the scleritis itself and affect the approach to therapy.
All patients suspected of scleritis should be urgently referred for evaluation by an ophthalmologist for a diagnostic evaluation that typically includes a slit-lamp examination, as well as ophthalmoscopy.
Diagnosis of scleritis — The diagnosis of anterior scleritis can generally be made in a patient who has eye pain and local tenderness to touch (tested by exerting pressure on the overlying eyelid) associated with violaceous redness of the eye, and based upon findings of scleral edema with dilatation of the deep episcleral vascular plexus on ophthalmologic examination (slit-lamp examination and ophthalmoscopy). Subtypes of anterior scleritis are differentiated by additional distinct physical examination findings. (See 'Ocular examination' above.)
Posterior scleritis, which is usually NOT accompanied by anterior scleritis, differs from anterior scleritis in that the eye appears "quiet," meaning white and uninflamed on external exam, rather than violaceous or red. The other findings of posterior scleritis, such as choroidal thickening and other changes such as exudative retinal detachment (see 'Ocular examination' above), are difficult for the non-ophthalmologist to identify, as they need full posterior segment ophthalmoscopy. In addition to slit-lamp examination and ophthalmoscopy, B-scan ultrasonography of the posterior pole is used to detect characteristic changes in posterior scleritis.
Anterior scleritis is usually readily apparent to both the patient and clinician and can be diagnosed and classified based upon its clinical features, elicited in the history and evident on the ophthalmologic examination (see 'Clinical features' above). By comparison, posterior scleritis is often less apparent and has variable clinical manifestations that may overlap on a spectrum with other clinical entities, such as inflammatory orbital "pseudotumor" [3,4].
●History – The history should include questions to elicit the eye-related symptoms and findings observed by the patient, including pain and its characteristics, including radiation; whether pain is worse with eye movement; symptoms of visual disturbance; and ocular redness. The duration and acuity of symptoms is an important feature to ascertain, given the typical subacute presentation in most patients. In addition, patients should be questioned regarding symptoms or findings of associated systemic disease that may further increase the likelihood of the diagnosis. (See 'Diagnostic evaluation for systemic disease' below.)
●Eye exam – All patients suspected of scleritis should be urgently referred for evaluation by an ophthalmologist for a diagnostic evaluation that typically includes a slit-lamp examination, as well as ophthalmoscopy. Patients who should generally undergo such ophthalmologic evaluation also include those with exophthalmos, especially unilateral or asymmetric exophthalmos (or proptosis), in whom the presentation is not thought to be due to dysthyroid disease (Graves).
●Imaging to evaluate scleritis – Several types of imaging studies may be used by the ophthalmologist in the evaluation of scleritis, depending upon the symptoms and findings:
•Ultrasonography – B-scan ultrasonography can confirm the scleral thickening that is the hallmark of the disease. Imaging of the posterior pole is a critical aspect in the evaluation and diagnosis of suspected posterior scleritis.
•Cross-sectional imaging – Computed tomography (CT) and magnetic resonance imaging (MRI) may be needed to exclude orbital lesions, particularly in patients with possible exophthalmos and cases of suspected or known granulomatosis with polyangiitis, which may be complicated by orbital inflammatory disease [13].
●Biopsy – Although it is typically not required, on rare occasions the ophthalmologist may obtain a tissue biopsy for the purpose of diagnosis. The usual indication for episcleral biopsy is for the exclusion of an infiltrative process such as sarcoidosis or a lymphoproliferative disorder. In a setting of acute scleritis after recent ocular surgery, an infectious cause needs to be strongly considered. Should these cases not respond to empirical antibiotic therapy, a biopsy may be helpful.
Larger procedures are occasionally required to diagnose the nature of a retrobulbar mass, which may occur, for example, in patients with an orbital abscess, lymphoma, or granulomatosis with polyangiitis.
Diagnostic evaluation for systemic disease — All patients with suspected scleritis should undergo a thorough evaluation for an associated systemic condition. This evaluation is typically performed by a rheumatologist. This should include:
●History and examination – Although the ocular complaints and findings are the most prominent disease feature for many patients with scleritis, critical clues to the presence of a systemic inflammatory condition may be present on the general history and physical examination.
The clinician should question the patient regarding any history of rheumatoid arthritis or other systemic autoimmune or inflammatory condition that may be associated with scleritis (table 1), such as granulomatosis with polyangiitis, and less often other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides; inflammatory bowel disease; systemic lupus erythematosus; relapsing polychondritis; spondyloarthritis; or recent eye surgery.
Patients should be specifically queried directly through a careful review of systems about constitutional symptoms and other organ system involvement, such as joint pain or swelling; abdominal pain, diarrhea, blood, or mucous in the stool; and symptoms of sinus congestion or other upper or lower airway symptoms. In addition, the clinician must examine with particular care the skin, joints, ears, nose, mouth, heart, lungs, and peripheral nerves, as these organs are often affected by the types of systemic disorders associated with scleritis. (See 'Systemic disease associations' above.)
●Laboratory assessment – Selected investigations should be guided by findings from the history and general physical examination (table 2). Both routine and specialized serologic assays are important in the evaluation of patients with scleritis [7,14]. The following routine tests and specialized serologic assays should be obtained to exclude or identify systemic disease:
•Routine tests:
-Complete blood count – Patients with systemic inflammatory conditions frequently have abnormalities of the white blood cell count, platelet count, or hematocrit.
-Serum chemistry profile – This should include creatinine, blood urea nitrogen, electrolytes, albumin, total protein, and aminotransferases.
-Urinalysis with microscopy – Urinalysis with microscopic examination of the urine sediment is essential to excluding glomerulonephritis, a common occurrence in some of the systemic diseases associated with scleritis, particularly granulomatosis with polyangiitis and systemic lupus erythematosus.
-Acute phase reactants – Patients with scleritis associated with a systemic illness are likely to have extremely high acute phase reactants. Both the erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) should be checked. These markers may also be useful in following responses to therapy and in detecting disease flares.
•Specialized serologic assays:
-Rheumatoid factor – A positive rheumatoid factor assay is a nonspecific result, but extremely high titers of rheumatoid factor are usually found in the setting of rheumatoid vasculitis. (See "Clinical manifestations and diagnosis of rheumatoid vasculitis" and "Rheumatoid factor: Biology and utility of measurement".)
-Antibodies to cyclic citrullinated peptides – Antibodies to cyclic citrullinated peptides (anti-CCP antibodies) have a high specificity for rheumatoid arthritis. (See "Biologic markers in the diagnosis and assessment of rheumatoid arthritis".)
-ANCA testing – ANCA assays are likely to be positive in patients with granulomatosis with polyangiitis, microscopic polyangiitis, or eosinophilic granulomatosis with polyangiitis (Churg-Strauss), particularly in cases associated with scleritis. (See "Clinical spectrum of antineutrophil cytoplasmic autoantibodies".)
If an immunofluorescence assay is positive in either a cytoplasmic or perinuclear pattern (ie, C-ANCA or P-ANCA), then confirmation of the presence of the type of ANCA associated with systemic vasculitis is important, through enzyme immunoassays for antibodies to proteinase-3 or myeloperoxidase.
-Antinuclear antibody testing – Antinuclear antibody (ANA) testing is useful for the exclusion of connective tissue diseases related to systemic lupus erythematosus. A strongly positive ANA assay should be followed by additional serological testing to determine the specific disease state responsible for the ANA positivity. This additional testing may include serum complement levels (C3, C4), antibodies to double-stranded deoxyribonucleic acid (DNA), and antibodies to the Ro, La, Sm, or RNP antigens. (See "Measurement and clinical significance of antinuclear antibodies".)
-Microbial serologies – In patients suspected of an infectious cause, serologic studies for Lyme disease and syphilis should be performed. Serologic studies for Bartonella should be performed in patients suspected of this condition. (See "Diagnosis of Lyme disease" and "Syphilis: Screening and diagnostic testing" and "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease".)
●Imaging studies – Chest radiography (plain films) should be performed in all patients to exclude infiltrates and nodules that might be associated with vasculitis, sarcoidosis, or infections such as tuberculosis. Abnormal findings on chest radiographs should be defined further with CT examination of the lungs and other imaging as required.
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of conditions that may cause eye pain or redness of the eye is broad, but an expert ophthalmologic examination is generally the key element in the evaluation to distinguish scleritis from other diagnostic possibilities. The differential diagnosis of the red eye encompasses the conditions that should be considered in the differential diagnosis of scleritis and is discussed in detail separately. (See "The red eye: Evaluation and management".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Uveitis".)
SUMMARY
●Scleritis is a painful, destructive disorder that may cause visual loss and may also be associated with inflammation in other parts of the eye, such as the cornea, episclera, and uveal tract. (See 'Introduction' above.)
●The sclera is divided into an anterior and posterior portion. Anterior scleritis and posterior scleritis have different sets of implications for diagnosis, treatment, and prognosis. (See 'Scleritis subtypes' above.)
•Anterior scleritis is subclassified into several subtypes:
-Diffuse anterior scleritis
-Nodular anterior scleritis
-Necrotizing anterior scleritis, which has two forms: necrotizing anterior scleritis with inflammation and scleromalacia perforans
•Diffuse, nodular, and necrotizing variants of posterior scleritis have also been identified, but the clinical distinction between these entities is more difficult due to anatomic challenges involved in the assessment of posterior scleritis. (See 'Scleritis subtypes' above.)
●Scleritis is associated with a systemic disease in approximately 50 percent of cases. Most are rheumatic diseases (particularly rheumatoid arthritis and granulomatosis with polyangiitis). Most of the remaining cases are due to infection. (See 'Systemic disease associations' above.)
●In many patients, scleritis is a manifestation of necrotizing vasculitis, often associated with immune complex deposition in blood vessel walls, granulomatous inflammation, thrombotic occlusion of blood vessels, and fibrinoid necrosis. (See 'Pathophysiology' above.)
●Anterior scleritis (with ocular erythema and other examination features as well as intense pain) is usually obvious to both the patient and clinician. Posterior scleritis is less obvious, as redness and other changes are often not seen on examination. (See 'Clinical features' above.)
Necrotizing anterior scleritis is particularly likely to involve other ocular structures, such as the cornea (peripheral ulcerative keratitis [PUK]), episclera, and uveal tract. (See 'Involvement of other ocular structures' above.)
●Patients suspected of scleritis based upon the medical history and, if present, findings of a red eye and pain with ocular movement, should be referred for urgent ophthalmologic evaluation. The diagnosis is made based upon the medical history and findings on slit-lamp examination and ophthalmoscopy of scleral edema with dilatation of the deep episcleral vascular plexus. Diffuse anterior, nodular, and necrotizing scleritis subtypes can be distinguished readily on physical examination, particularly when a slit lamp is used.
In addition, both ultrasonography and cross-sectional imaging studies of the orbit are useful in diagnosing posterior scleritis. (See 'Diagnosis of scleritis' above.)
●The differential diagnosis of scleritis is broad, but most conditions that may mimic or share features with scleritis can be readily distinguished by the ophthalmologic evaluation, including slit-lamp examination and ophthalmoscopy. (See "The red eye: Evaluation and management".)
●History and examination, with particular attention to disorders that may be associated with scleritis, such as rheumatoid arthritis or granulomatosis with polyangiitis, and both routine and specialized serologic assays are important in the exclusion of systemic diseases. (See 'Diagnostic evaluation for systemic disease' above.)
The following laboratory tests and imaging should be obtained:
•Complete blood count
•Serum chemistry profile
•Urinalysis with microscopy
•Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
•Rheumatoid factor
•Anti-cyclic citrullinated peptide (anti-CCP) antibodies
•Antineutrophil cytoplasmic antibody (ANCA) testing
•Antinuclear antibody (ANA) testing
•Chest imaging (radiograph and, if positive, CT of the chest), which is helpful in excluding systemic diseases
Tissue biopsy is seldom required for diagnosis of scleritis but is occasionally performed to exclude infiltrative or malignant disorders.
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges John Stone, MD, who contributed to an earlier version of this topic review.
