Major ReviewScleritis
Introduction
Scleritis is defined as inflammation of the sclera, and it has a characteristic clinical picture. It is typically a severe painful inflammatory process centered in the sclera that may involve the cornea, adjacent episclera, and underlying uvea; it poses a significant threat to vision. Up to 50% of patients with scleritis have evidence of an underlying systemic disease. Scleritis is usually suspected from the clinical history, and it is confirmed by its characteristic clinical signs. When the posterior sclera is involved, clinical signs may be less obvious and ultrasonography or other imaging studies may be necessary to confirm the diagnosis.
In order to understand the pathophysiology of this condition, a review of ocular surface anatomy is required. The sclera is an incomplete shell comprising approximately 90% of the outer coat of the eye; it begins at the limbus and terminates at the optic canal. The sclera is composed of extracellular matrix—collagen, elastin, proteoglycans, the bundles of which run in whorls and loops. The innermost part of the sclera is the lamina fusca, which has many grooves caused by the passage of ciliary vessels and nerves. Anteriorly, the sclera is continuous with the cornea at the corneoscleral junction, and lying just posterior to this, within the sclera, is the canal of Schlemm. Posterior to the canal is the scleral spur, which is triangular with its apex pointing anteriorly and inward and attaching to the ciliary body. The posterior pole of the sclera is weakened and has a sieve-like appearance (lamina cribrosa) where it is perforated by the axons of the optic nerve. Here, the sclera is fused with the dura mater and arachnoid sheaths of the optic nerve, hence explaining the optic nerve swelling seen in 43% of eyes with posterior scleritis.17 The sclera has a rich sensory innervation from the ciliary nerves, which pierce the sclera around the optic nerve. Many short posterior ciliary nerves supply the posterior portions and two long posterior ciliary nerves supply the anterior region. Because the extraocular muscles are inserted into the sclera, the dull ache of scleral inflammation is made worse by ocular movement.116
In order to reliably differentiate episcleritis and scleritis, an understanding of the anatomy of the vascular plexuses contained within the conjunctiva, episclera, and sclera is essential. There is a vascular plexus of vessels within the conjunctiva and two vascular layers within the episclera, superficial and deep. The sclera itself is avascular, and, therefore, highly dependent on the vascular coats on either side. Anteriorly, the episclera has a rich blood supply from the anterior ciliary arteries, which form a rich plexus deep to the conjunctiva. These vessels form extensive collateral arterial anastomoses with the posterior ciliary arteries at the root of the iris and are normally inconspicuous but become visibly congested in the presence of inflammation.116 The anterior vascular system is readily visible with the slit-lamp and can be imaged by fluorescein angiography.127 The superficial episcleral capillary plexus is a radially arranged series of vessels, which anastomose at the limbus with the conjunctival vessels and with the deep plexus. The deep episcleral capillary network is closely applied to the sclera. Posteriorly, four vortex veins drain the choroidal circulation, pierce the sclera posterior to the equator, and join the ophthalmic vein.116
Scleritis is often confused with episcleritis, which is inflammation confined to the superficial episcleral tissue and does not involve the deep episcleral tissue that overlies the sclera. Episcleritis is a mild non-vision-threatening form of ocular inflammation that is usually idiopathic in nature and is not usually associated with involvement of other ocular structures although adjacent corneal involvement can be seen and the intraocular pressure may be raised. The clinical differentiation of episcleritis and scleritis involves a detailed history and a careful ocular examination to determine which layers of the wall of the eye are involved by inflammation. Differentiation is important at presentation as management, prognosis, and complications are very different for these two diseases and long term studies have shown that very few patients progress from one to develop the other.107, 121
To sort out the clinical signs it is essential to understand the anatomy of the episclera and sclera, the vascular plexuses contained therein, and to appreciate the examination techniques that allow this determination. The key clinical observations in patients with scleral inflammation involve determining the relationship of the vascular plexuses to each other and the site of maximal vascular involvement, best seen with red-free light on slit-lamp biomicroscopy. In episcleritis, the conjunctival and superficial episcleral vascular plexuses are displaced outward from the sclera and the underlying deep episcleral plexus is uninvolved and flat against normal-thickness scleral tissue. In scleritis all vascular layers may be involved but the maximal involvement is in the deep episcleral plexus, which is displaced outward by edematous swollen sclera. This displacement of the deep episcleral vessels is seen only in patients with scleritis.
In episcleritis the patient's main complaint is often redness, which may also be associated with a feeling of grittiness. This is in contrast to scleral inflammation, where pain is much more prominent along with globe tenderness and redness that may involve the whole eye or just a small localized area. The vascular engorgement of the deep episcleral plexus in scleritis has a characteristic bluish-violet hue, which is not present in patients with episcleritis, in which case the engorgement of the superficial episcleral plexus has a distinct red hue. Episcleritis may be associated with nodules and may overly an area of anterior scleritis. Examination in natural daylight can be extremely useful allowing the detection of these subtle color differences that are often not appreciable using the slit-lamp. Additionally, slit-lamp examination with red-free light and diffuse illumination accentuates visibility of blood vessels and areas of capillary nonperfusion. In addition, the conjunctival and superficial vessels can be blanched with 2.5–10% phenylephrine or 1:1,000 epinephrine while the deep vessels are hardly affected.
Section snippets
Immunopathology
Most eyes with scleritis do not come to biopsy or to enucleation. In one study of enucleated eyes, eyes with necrotizing scleritis showed vasculitis with fibrinoid necrosis and neutrophil invasion of the vessel wall in 75%, and vascular immunodeposits were found in 93% in the scleral tissue. In addition, there was a significant increase in the number of inflammatory cells, including T cells of all types and macrophages. HLA-DR expression was dramatically increased.29 Studies of deep episcleral
Classification of Scleral Inflammation
The classification system devised by Watson is accepted as the most clinically useful. It is anatomically based and is detailed in Table 1. Episcleritis is recognizable in the anterior episclera as a diffuse process or less commonly as a nodular form of episcleral inflammation. Posterior episcleritis occurs and has been documented pathologically but is not recognizable as a clinical entity.
Scleritis may involve the anterior sclera, posterior sclera or both.107 Anterior scleritis is the most
Presentation of Scleritis
Patients with scleritis may present in one of two ways—they may already be known to have an underlying related disorder, such as rheumatoid arthritis, or the scleritis may present de novo in the absence of any known underlying systemic disease.107 The characteristic feature of scleritis is the severe pain that may involve the eye and orbit and radiates to involve the ear, scalp, face, and jaw. Scleritic pain is typically dull and boring in nature, exacerbated by eye movement, is worse at night
Signs
The signs of scleritis depend on the location of the scleritis and its severity.107 The hallmark signs of scleral inflammation are the development of scleral edema and dilatation or closure of the deep episcleral vascular plexus. Each pattern of scleritis has physical signs that allow its recognition and are described below.
Demographic Data
Patients with scleritis are predominantly middle-aged and Caucasian with a mean age at onset of 49 years.77 Female patients comprise 71% of all patients with scleritis45 and 65% of patients with posterior scleritis.77 In 30% of patients, posterior scleritis occurred before the age of 40 years. Interestingly, in a small series of patients from the West Indies a preponderance of male patients was seen with posterior scleritis, who also tend to be much younger (mean age 19 years) at presentation.17
Classification by Etiology
The incidence of systemic disease in patients with scleritis is reported as 39–50%.45, 77, 104 There is no known HLA association.49 It is useful to note that the association of posterior scleritis with anterior scleritis is much more likely to occur in a patient in whom there is an underlying systemic disease.77
Investigation of Patients With Scleritis
Blood tests for diagnosis of inflammation and systemic disease are commonly used in the investigation of these patients. In any acute presentation it is important to obtain an assessment of the patients' blood pressure, renal function (including urine analysis) and the acute phase response (normochromic normocytic anaemia, raised neutrophils platelets, Erythrocyte sedimentation rate, C-reactive protein and plasma viscosity, reduced serum albumin) in order to get an idea of the degree of
Management of Patients With Scleritis
Patients with scleritis need to have the type and extent of their disease diagnosed, the complications present detected and any underlying systemic or local cause defined. The aim of treatment is to remove or treat the cause where possible but in the majority is to control the inflammatory process to relieve the pain and thereby reduce the damage to the eye.75
Outcome
The aims of treatment are to control inflammation, eliminate pain, and reduce the occurrences of complications and also to treat any associated systemic disease. It is also important to adequately treat scleritis patients because systemic disease in this group has an associated increased mortality in patients presenting with scleritis.2, 30 Loss of vision is much more common in eyes with posterior scleritis and has been noted in 30% of patients who in one study lost 2 or more lines of Snellen
Conclusion
Scleritis is an ocular disease that may be difficult to diagnose and manage. However, with informed and adequate care the long-term prognosis can be excellent both for the patient and the eye and every attempt should be made to achieve this with careful clinical history taking, detailed ocular examination, and the use of immunosuppressant drugs when necessary.
Method of Literature Search
This article was prepared using the National Library of Medicine database 1975–2004 using the following search words: scleritis or ocular or eye or episcleritis or scleral, and one of the following: necrotising, systemic, immunosuppression, infectious, sclerokeratitis, corneoscleritis, acanthamoeba, zoster, varicella, Borrelia, leprosy, mycobacterium, aspergillus, buckle, polyarteritis nodosa, sarcoidosis, anticytoplasmic, vasculitic, granulomatosis, rheumatic, arthritis, scleromalacia,
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