14/4/24, 16:30 Clinical manifestations and diagnosis of scleritis - UpToDate

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Clinical manifestations and diagnosis of scleritis

AUTHOR: Reza Dana, MD, MPH, MSc
SECTION EDITOR: Jennifer E Thorne, MD, PhD
DEPUTY EDITOR: Siobhan M Case, MD, MHS

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2024.

This topic last updated: Mar 25, 2024.

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 (RA) or granulomatosis with polyangiitis (GPA)
[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

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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 females, 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.

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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 (RA) is the most common; it may
also rarely occur in patients with granulomatosis with polyangiitis (GPA). (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. Approximately
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.

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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. In a retrospective study of 243 patients at a tertiary
referral center, 47 percent had an underlying systemic disease including various types of
rheumatic diseases (most commonly rheumatoid arthritis [RA]) in 37 percent of patients and
infection (most commonly herpes zoster) in 7 percent of patients [7]. Scleritis may be the
initial presentation of these systemic diseases; among the patients with an associated
medical condition, only 78 percent had the relevant diagnosis at the onset of ocular disease.
Systemic vasculitides, including antineutrophil cytoplasmic antibody (ANCA)-related
conditions, were the most common conditions that had not been diagnosed prior to the
onset of eye disease.

Specific types of systemic diseases that are associated with scleritis include the following
( table 1):

● Systemic rheumatic diseases – A wide variety of systemic rheumatic diseases are

associated with scleritis, including RA [8], various types of vasculitis, and, less
commonly, systemic lupus erythematosus [9], reactive arthritis, and relapsing
polychondritis [10].

• Rheumatoid arthritis – RA is the systemic disease that is most commonly

associated with scleritis. 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".)

• Vasculitis – Granulomatosis with polyangiitis (GPA), 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 ANCA, such as microscopic polyangiitis
(MPA) and eosinophilic granulomatosis with polyangiitis (eGPA, Churg-Strauss) [11].
(See "Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical
manifestations and diagnosis", section on 'Ophthalmic and orbital involvement'.)

● Infection – Systemic infections associated with scleritis include herpes zoster [12] and,
less commonly, Lyme disease [13], tuberculosis [14], syphilis [15], and aspergillus [16].
(See "Tuberculosis and the eye" and "Neurosyphilis".)

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● Local trauma – Local trauma may also be a contributing factor. Scleritis may first occur
after ocular surgery, perhaps initiated by trauma to the sclera [17-19]. The risk may be
greater in patients with underlying rheumatic disease [17,18].

● Other conditions – Other systemic conditions associated with scleritis include

sarcoidosis [20] and inflammatory bowel disease [21].

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

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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).

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• 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 [22]. (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.

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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
examination, 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

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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 examination – 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 (GPA), which may be complicated by orbital inflammatory disease [23].

● 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
GPA.

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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
(RA) or other systemic autoimmune or inflammatory condition that may be associated
with scleritis ( table 1), such as GPA 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 [11,24]. 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 GPA and systemic lupus erythematosus.

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- 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 RA. (See "Biologic
markers in the assessment of rheumatoid arthritis".)

- ANCA testing – ANCA assays are likely to be positive in patients with GPA,
microscopic polyangiitis, or eosinophilic granulomatosis with polyangiitis (eGPA,
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 (dsDNA), 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".)

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● 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 subtypes – 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. 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 'Introduction' above and 'Scleritis subtypes'
above.)

• Anterior scleritis – Anterior scleritis is subclassified into several subtypes (see

'Anterior scleritis' above):

- Diffuse anterior scleritis

- Nodular anterior scleritis
- Necrotizing anterior scleritis, which has two forms: necrotizing anterior scleritis
with inflammation and scleromalacia perforans

• 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.
(See 'Posterior scleritis' above.)

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● Pathogenesis

• Pathophysiology – 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.)

• Systemic disease associations – Scleritis is associated with a systemic disease in

approximately 50 percent of cases ( table 1). Most are rheumatic diseases
(particularly rheumatoid arthritis [RA] and granulomatosis with polyangiitis [GPA]).
Most of the remaining cases are due to infection. (See 'Systemic disease
associations' above.)

● Clinical features

• Ocular symptoms and examination – 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 'Ocular symptoms' above and 'Ocular
examination' above.)

• Involvement of other ocular structures – 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.)

● Diagnosis

• Diagnosis of scleritis – 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.)

• Diagnostic evaluation for systemic disease – History and examination, with

particular attention to disorders that may be associated with scleritis, such as RA or
GPA, and both routine and specialized serologic assays are important in the

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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.

● Differential diagnosis – 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 'Differential diagnosis' above and "The red eye: Evaluation and
management".)

ACKNOWLEDGMENT

The UpToDate editorial staff acknowledges John Stone, MD, who contributed to an earlier
version of this topic review.

Use of UpToDate is subject to the Terms of Use.

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Rheumatoid Arthritis: A Clinical Case Report Supported by A Brief Review with Risk of
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relapsing polychondritis. Br J Ophthalmol 2016; 100:1290.
11. Hoang LT, Lim LL, Vaillant B, et al. Antineutrophil cytoplasmic antibody-associated active
scleritis. Arch Ophthalmol 2008; 126:651.
12. Tranos PG, Ong T, Nolan W, et al. Posterior scleritis presenting with annular choroidal
detachment as a complication of herpes zoster ophthalmicus. Retina 2003; 23:716.

13. Berkenstock MK, Long K, Miller JB, et al. Scleritis in Lyme Disease. Am J Ophthalmol
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14. Sainz de La Maza M, Hernanz I, Moll-Udina A, et al. Presumed tuberculosis-related
scleritis. Br J Ophthalmol 2023; 107:495.
15. Casey R, Flowers CW Jr, Jones DD, Scott L. Anterior nodular scleritis secondary to syphilis.
Arch Ophthalmol 1996; 114:1015.

16. Fincher T, Fulcher SF. Diagnostic and therapeutic challenge of Aspergillus flavus scleritis.
Cornea 2007; 26:618.
17. Sainz de la Maza M, Foster CS. Necrotizing scleritis after ocular surgery. A
clinicopathologic study. Ophthalmology 1991; 98:1720.
18. Díaz-Valle D, Benítez del Castillo JM, Castillo A, et al. Immunologic and clinical evaluation
of postsurgical necrotizing sclerocorneal ulceration. Cornea 1998; 17:371.
19. Scott JA, Clearkin LG. Surgically induced diffuse scleritis following cataract surgery. Eye
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20. Dursun D, Akova YA, Bilezikçi B. Scleritis associated with sarcoidosis. Ocul Immunol
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21. Soukiasian SH, Foster CS, Raizman MB. Treatment strategies for scleritis and uveitis
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22. Squirrell DM, Winfield J, Amos RS. Peripheral ulcerative keratitis 'corneal melt' and
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GRAPHICS

Bilateral scleritis

Bilateral anterior scleritis in a patient with Cogan syndrome, manifested by ocular pain and erythema.
(The patient also had vertigo and bilateral sensorineural hearing loss as a complication of her Cogan
syndrome.)

Graphic 81098 Version 3.0

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Anatomy of the anterior segment of the eye

Graphic 62615 Version 4.0

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Posterior scleritis

Posterior scleral wall inflammation with involvement of the optic disc. The disc margin is blurred in
association with vascular engorgement and flame-shaped nerve fiber layer hemorrhages.

Courtesy of Reza Dana, MD, MSc, MPH.

Graphic 65671 Version 2.0

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Diffuse anterior scleritis

The anterior sclera reveals diffuse redness and vascular engorgement.

Courtesy of Reza Dana, MD, MSc, MPH.

Graphic 55397 Version 4.0

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Nodular anterior scleritis

Nodular anterior scleritis in a patient with rheumatoid arthritis. Nodular elevation of the sclera is
surrounded by deep scleral vascular engorgement.

Courtesy of Reza Dana, MD, MSc, MPH.

Graphic 55940 Version 2.0

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Acute necrotizing anterior scleritis with inflammation

Acute necrotizing scleritis with inflammation in a patient with rheumatoid arthritis. Anterior bulging of
the inflamed sclera is seen in association with scleral thinning due to necrosis.

Courtesy of Reza Dana, MD, MSc, MPH.

Graphic 81029 Version 3.0

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Chronic necrotizing anterior scleritis with inflammation

Chronic necrotizing anterior scleritis with inflammation in a patient with granulomatosis with
polyangiitis. Significant thinning of the sclera permits the visualization of the underlying choroid
through the scleral wall.

Courtesy of Reza Dana, MD, MSc, MPH.

Graphic 81136 Version 4.0

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Scleromalacia perforans

Scleromalacia perforans in a patient with rheumatoid arthritis. There are areas of significant collagen
breakdown in the scleral wall with little to no associated redness or vascular engorgement.

Courtesy of Reza Dana, MD, MSc, MPH.

Graphic 78096 Version 2.0

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Systemic diseases associated with scleritis

Connective tissue diseases

Rheumatoid arthritis

Reactive arthritis

Systemic lupus erythematosus

Relapsing polychondritis

Systemic vasculitides
Granulomatosis with polyangiitis

Microscopic polyangiitis

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

Polyarteritis nodosa

Cogan syndrome

Behçet syndrome

Urticarial vasculitis

Infections

Syphilis

Tuberculosis

Lyme disease

Herpes zoster

Aspergillis

Other
Sarcoidosis

Inflammatory bowel disease

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Possible laboratory investigations for patients with episcleritis or scleritis

Blood and serologic testing

Complete blood count

Erythrocyte sedimentation rate

Antinuclear antibody

Syphilis serologies

Rheumatoid factor

Angiotensin-converting enzyme levels

Antineutrophil cytoplasmic antibody

Serum uric acid concentration

Urinalysis

Skin tests
Tuberculin skin test

Allergy tests

Radiologic testing
Chest radiograph

Sacroiliac joint radiographs

These recommendations should be modified as dictated by the findings of a thorough history, review
of systems, and physical examination.

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