Introduction
Scleritis is a rare inflammatory disease which affects the sclera and its adjacent structures such as the episclera, uvea, and cornea. Scleritis can cause severe, disabling pain, destruction of scleral tissue, and the risk of significant visual loss.
The pathophysiology of scleritis is complex, incompletely understood, and complicated by the heterogeneity of the disease as well as the dearth of studies into the immunopathology.
Clinical background
Classification of scleritis
Scleritis may be classified anatomically and by histopathology. The most widely accepted method of classification of scleritis is that described by Watson et al in the 1960s ( Table 82.1 ).
| Anatomical classification | Histological description | Clinical features of scleritis | |
|---|---|---|---|
| Episcleritis | Anterior | Nodular | |
| Simple | |||
| Scleritis | Anterior | Nodular | A nodule is a localized edematous area, giving the sclera an elevated smooth, rounded appearance. A scleral nodule is usually very tender and can accompany a diffuse scleritis. It can be single or multiple |
| Diffuse | Margins of scleral involvement are ill defined, may be localized to an area of sclera, or may be extensive. Anterior scleritis is bilateral in 50% of cases. During an episode of scleritis the area of redness can migrate to occupy different areas or recur in different areas | ||
| Necrotizing with inflammation | All of the above features may be present. There is an avascular area in acute inflammation which is white in appearance. This leads to necrosis, thinning of the cornea, and sometimes perforation | ||
| Necrotizing without inflammation | Scleromalacia perforans. This is seen most frequently in rheumatoid arthritis. Despite the degree of thinning of the sclera, perforation rarely occurs | ||
| Posterior |
| Accounts for 7% of cases of scleritis. It usually presents with periorbital pain, worse with eye movement or headache. The pain is often exacerbated with eye movement. One-third present with visual loss. If an anterior scleritis also exists then the likelihood of there being a systemic disease also increases. Other features include serous retinal detachment, swollen optic disc, and optic atrophy, subretinal granulomas, macular edema, choroidal folds at the macula and elsewhere, and choroidal effusions |
Historical development and demographic data
Scleritis was described in 1702. An early description of scleritis distinguishing it from episcleritis was made in 1830, as reported by Watson and Hayreh in 1976. The prevalence of scleritis has been estimated at 8 cases in 100 000 and the incidence at 1.3 cases per 100 000 person-years. There are no described racial or geographic differences. Females are affected slightly more frequently by scleritis (1.6 : 1). It can affect any age but is rarely observed in children. The mean age of onset of scleritis is 45–60 years.
Clinical features of scleritis
Key ocular signs and symptoms
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Pain in scleritis is the main symptom. It can be severe, gnawing, or boring in nature and can affect sleep.
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Scleritis is often painless in chronic rheumatoid arthritis when the presentation is scleromalacia perforans, which is an extra-articular manifestation of rheumatoid arthritis.
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Redness of the sclera due to dilation and hypervascularity of scleral and episcleral vessels gives the eye a bloodshot appearance ( Figure 82.1 ). Redness of the sclera may be:
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Localized to one or more sectors of the sclera
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Diffuse.
Figure 82.1
(A) Nonnecrotizing anterior scleritis. (B) Necrotizing anterior scleritis (note white area of necrosis and scleral thinning (box)). (C) Ocular coherence tomography showing macular edema and retinal pigment epithelium detachment in posterior scleritis.
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Scleral thinning and reorganization of scleral collagen fibrils cause translucency of the sclera and a bluish appearance ( Figure 82.1 ).
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Posterior scleritis is typically painful at rest and on eye movement. Redness may not be visible. Occasionally posterior scleritis may be painless.
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Risk factors for an underlying systemic disease include bilateral disease, necrotizing scleritis, scleromalacia perforans, a positive rheumatoid factor, or antineutrophil cytoplasmic antibody (ANCA) test.
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An episodic nature of disease may suggest a diagnosis such as relapsing polychondritis or inflammatory bowel disease.
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Corneal changes may also occur in scleritis, causing a sclerokeratitis.
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Scleritis may accompany other ocular signs such as an orbital inflammatory mass in Wegener’s granulomatosis.
Diagnostic workup
Nearly 50% of patients with scleritis have an underlying systemic disease identifiable on medical examination ( Box 82.1 ). The systemic associations with scleritis are summarized in Table 82.2 along with appropriate tests for each condition.
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Most cases of scleritis that are associated with disease have symptoms of systemic disease at the time of presentation
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In the vasculitides scleritis may be the presenting feature
| Systemic disease association with scleritis | Frequency of scleritis occurring in the systemic disease | Associated ocular features | Main manifestations of systemic disease | Serological markers which may be associated with systemic disease |
|---|---|---|---|---|
| Rheumatoid arthritis | 0.6% |
|
| RhF+ in nodular scleritis or scleromalacia perforans |
| Inflammatory bowel disease | 18% | Nodular anterior uveitis |
| Colonoscopy + biopsy |
| Wegener’s granulomatosis | <10% |
|
|
|
| Relapsing polychondritis | 40% | Episcleritis |
|
|
| Spondyloarthropathy (psoriatic, reactive arthritis, AS) * | 0.04% † | Anterior uveitis | Spondyloarthropathy |
|
| Systemic lupus erythematosus | <2% |
|
|
|
| Polyarteritis nodosa | Rare | Peripheral ulcerative keratitis | Abdominal arteriogram | |
| Cogan’s disease | Rare | Interstitial keratitis |
| Biopsy |
| Microscopic polyarteritis | Rare | Pulmonary vasculitis | pANCA | |
| Churg–Strauss syndrome | Rare | Pulmonary vasculitis | pANCA | |
| Takayasu arteritis | Rare |
| MRA ± arteriogram | |
| Giant cell arteritis * | Very rare | Bitemporal headache, weight loss, polymyalgia | High ESR. Temporal artery biopsy | |
| Tophaceous gout | Very rare | Uric acid |
* Causes an anterior ischemia which may cause scleritis.
† Prevalence of spondyloarthropathies in the population is approximately 2 in 1000. If 2% of scleritis is caused by spondyloarthropathy then the frequency at which scleritis occurs in this disease may be approximated to 0.04%.
Tests and investigations in scleritis
Making a diagnosis of scleritis is usually done on clinical grounds, with the exception of the B scan in posterior scleritis ( Figure 82.2 ). There are a few tests that would be recommended as screening tests for all patients without an established cause ( Table 82.2 ). Other tests should be guided by systemic symptoms, clinical course, and/or exposure to infective agents.
In general, the typical panel of blood tests that all patients with scleritis should have is summarized in Table 82.3 . A recent study has proposed that a rheumatoid factor should also be obtained as a screening test.
| Test | Description of test | Comments |
|---|---|---|
| ANCA | Indirect immunofluorescence for presence and titer of antibodies in the cytoplasm of neutrophils | If this is positive, this may indicate presence of a vasculitis, indicating further workup and medical consultation |
| FTA | Immunoassay to diagnose syphilis. This is a rare cause of scleritis but it may have long latency and many presentations. It can be easily treated | A positive test may indicate untreated syphilis, previously treated syphilis, or a false-positive result |
| ESR | Indicator of nonspecific inflammation | If elevated it suggests the presence of active systemic disease |
| Chest X-ray (optional depending on risk factors for tuberculosis/lung disease) | X-ray imaging of the lung parenchyma and hilae | Hilar adenopathy in sarcoidosis. An apical calcified scar suggests previous tuberculosis. Parenchymal changes may indicate areas of vasculitis, fibrosis, or interstitial lung disease (seen in vasculites or rheumatoid arthritis) |
Significance of antineutrophil cytoplasmic antibodies
Antineutrophil antibodies (ANCA) are used as clinical markers of disease for a number of vasculitides. The most relevant disease associations in the context of scleritis are Wegener’s granulomatosis, polyarteritis nodosa, microscopic polyarteritis, and Churg–Strauss syndrome ( Box 82.2 ). ANCA is the recommended screening test as:
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A positive ANCA may be the presenting symptom of a systemic vasculitis.
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In a proportion of cases who present with apparently idiopathic scleritis, a positive ANCA may predict development of Wegener’s disease in some patients.
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Antineutrophil cytoplasmic antibody (ANCA)-positive scleritis – patients have more serious ocular disease, especially visually significant corneal complications
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ANCA-positive cases of scleritis are more likely to be associated with a systemic disease than ANCA-negative cases of scleritis
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Most ANCA-positive scleritis patients do not have a past history of immune-mediated disease
Perinuclear-staining ANCA (pANCA) tends to be linked with renal vasculitis and microscopic polyarteritis. Cytoplasmic-staining ANCA (cANCA) positivity is highly associated with Wegener’s granulomatosis. Sensitivity is 67% for patients with active systemic disease and specificity is 96%. There is sometimes clinical overlap in phenotypes of cANCA and pANCA systemic vasculitis; therefore the pANCA may be positive in a Wegener’s-like vasculitic picture.
Role of rheumatoid factor testing
In the general population (without rheumatoid arthritis) the prevalence of rheumatoid factor is around 15%. However, it has been suggested that, even in the absence of joint symptoms, a positive rheumatoid factor is an independent risk factor for developing rheumatoid arthritis. Anticitrullinated peptides are highly specific for RA. Their role in evaluating scleritis has not been studied.
Antinuclear antibodies (ANA) should be tested if scleritis secondary to systemic lupus erythematosus is in the differential diagnosis. In the general population 30% of females are ANA-positive so a positive ANA is not diagnostic of this condition.
Differential diagnosis
The most common differential diagnosis is episcleritis ( Tables 82.4 and 82.5 , Box 82.3 ).
| Imaging test | Indication for use | Features if test is abnormal |
|---|---|---|
| B-mode ultrasonography (10 Mz) (B scan) | Diagnosis of posterior scleritis | T sign indicating posterior scleral edema |
| Ultrasound biomicroscopy | Diagnosis of anterior scleritis and scleral necrosis | Scleral thickening and focal hyporeflectivity |
| Anterior-segment fluorescein angiography | Diagnosis of scleritis and necrosis | Hyperfluorescence and leakage from episcleral vessels. Areas of capillary shutdown |
| Posterior-segment fluorescein angiography | Investigate the differential of posterior scleritis or unexplained visual loss | Can assist in differential diagnosis of a fundal mass, and diagnose serous detachments, cystoid macular edema |
| Ocular coherence tomography | Posterior scleritis or unexplained visual loss | Cystoid macular edema and serous detachment |
| Computed tomography orbits | Additional test for posterior scleritis or where an inflammatory orbital mass is suspected |
|
| Magnetic resonance imaging orbits | If additional high-resolution information about the soft tissue is required | Generally not used to diagnose scleritis. May reveal orbital massor myositis |
| Episcleritis | Scleritis |
|---|---|
| Discomfort rather than severe pain | Pain usually severe. May be severe enough to disturb or prevent sleep. May cause pain on moving the eye |
| Redness of the episclera tends to be mild. Superficial phenylephrine 2.5% will blanch superficial episcleral vessels within 10 minutes |
|
| Responds to topical treatment or nonsteroidal anti-inflammatory | May additionally require systemic immunosuppression |
| Will not cause necrotization/scleral thinning | May cause a necrotizing process involving sclera and associated structures |
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Episcleritis is a more benign condition than scleritis, which affects the episclera
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It has a milder course than scleritis and does not affect vision
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Treatment of episcleritis rarely requires little more than topical treatment with steroids or nonsteroidal anti-inflammatory agents
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